Category Archives: Genetics

UC Berkeley Genetic Testing Affair: Science vs Science Education – guest post by Dr.Marie-Claire Shanahan

Marie-Claire Shanahan is an Assistant Professor of Science Education at the University of Alberta, in Edmonton, Alberta, Canada. As a former science teacher, she was always surprised by the ways that students talked themselves out of liking science – and she decided to do something about it. She now researches the social and cultural aspects of science and science education, especially those related to language and identity.

Marie-Claire and I first met online, then also in Real World when she attended ScienceOnline 2010, after which I interviewed her for my blog. You can check out her website and follow her on Twitter. Very interested in her scholarly work, I asked her if she would write a guest-post on one of her topics, and she very graciously agreed. Here is the post about the Berkeley genetic testing affair.

Outside of issues related to teaching evolution in schools, the words controversy and science education don’t often come into close contact with one another. It would be even rarer to be reporting on legislative intervention aimed at halting science education activities. So what’s going on with the UC Berkeley genetic testing affair?

News started to surface in May that Berkeley was going to be asking incoming first year and transfer students to send in a DNA swab. The idea was to stimulate discussion between students as part of the yearly On the Same Page program. A heated debate ensued that has ultimately lead to proposed state legislation that would bar California’s post secondary institutions from making unsolicited requests for DNA samples from students. Both the controversy and the legislation are excellently reported by Ferris Jabr at Scientific American here and here.

It would be reasonable to assume that this seems controversial because it involves genetic testing and therefore personal information. But is there more to it than that?

I chatted informally with some friends about the issue. One expressed her divided feelings about it saying (roughly quoted) “It seems like they [university admin] have addressed the ethical concerns well by being clear about the use of the swabs and the confidentiality but something still just doesn’t feel right. There’s still a part of me that shivers just a little bit.”

What is the shiver factor? Genetic testing and the idea that institutions might have access to our DNA do conjure some imaginative science fiction possibilities. So that could be causing the shivers. But from my perspective as a science education researcher, I think there’s also an underlying issue that makes this particular situation feel controversial: despite having science education goals, this looks and feels a lot more like science. That look and feel leads to confusion about how this initiative should be judged both from an ethical perspective and an educational one.

Science and science education are not the same thing (nor should they be). One way to think of them is through activity analysis, paying attention to who is involved, what are their objectives and what are the artefacts (e.g., tools, language, symbols), actions, and rules that those involved generally agree are used to accomplish the goals of the activity. Studies in activity theory emphasize the importance of shared understanding for accomplishing and progressing in any activity. I would argue that science and science education are different (though obviously related) activities. They have, in particular, different objectives and different artefacts, rules and actions that guide and shape them. As participants in one or the other (or both), teachers, parents, students, researchers, administrators have both tacit and explicit understandings of what each activity entails – what are the rules, the acceptable tools and practices and the appropriate language.

This is where the Berkeley project places itself in a fuzzy area. The objectives of the project are clearly stated to be educational. From the On the Same Page website: “we decided that involving students directly and personally in an assessment of genetic characteristics of personal relevance would capture their imaginations and lead to a deeper learning experience.” Okay, that sounds like the same reasons teachers and professors choose to do many activities. Sounds like science education.

But what about the tools? Testing students’ blood type or blood pressure uses tools commonly available in high school labs (or even at the drug store). The tools used here though are not commonly available – these samples are being sent to a laboratory for analysis. Participants don’t therefore have a shared perspective that these are the tools of education. They seem like the tools of science.

What about the language? One of the main publically accessible sources of information is the On the Same Page website, in particular an FAQ section for students. It starts with the questions: What new things are going on in the scientific community that make this a good time for an educational effort focused on personalized medicine? and Why did Berkeley decide to tackle the topic of Personalized Medicine? These are answered with appeals to educational discourse – to academic strengths, student opportunities, and the stature of Berkeley as an educational center. The agent or actor in the answers to these questions is the university as an educational institutional: “This type of broad, scholarly discussion of an important societal issue is what makes Berkeley special. From a learning perspective, our goal is to deliver a program that will enrich our students’ education and help contribute to an informed California citizenry.”

Beside these educational questions, however, are questions that are part of the usual language and processes of science: Will students be asked to provide “informed consent” for this test of their DNA? What about students who are minors? How can you assure the confidentiality and privacy of a student’s genetic information? What will happen to the data from this experiment? Has this project been approved by Berkeley’s Human Subjects Institutional Review Board? These questions are the questions that appear in human subjects information letters. They make this sound like this is science. The answers to these questions take a different perspective to the ones above. The technical terms are not educational ones but scientific ones. The actor in these responses is neither the educational institution nor the student as an educational participant but the student as a research object: “All students whether they are minors or not will be asked to provide informed consent. They will read and sign a detailed form describing exactly what will be done with their DNA sample, how the information will be used and secured for confidentiality, how this information might benefit them, and what the alternatives are to submitting a sample.”

Anyone who has done human subjects research will recognize this language is almost word for word from typical guidelines for informed consent documents. My consent forms usually don’t deal with DNA samples (usually something much less exotic, such as student writing or oral contributions during class) but the intent is the same. This language sets out the individuals under consideration as the objects of scientific research.

The overall effect is one of a mixed metaphor – is this research or is it teaching? Are the students actually acting in the role of students or are they the objects of research? What standards should we be using to judge if this is an appropriate action. The materials posted by UC Berkeley suggest that they believe this should be judged as an educational project. But the reaction of bioethicists and advocacy groups (such as the Council for Responsible Genetics) suggests that it be judged by research standards.

Why does it matter? Because the ethical considerations are different. As I said above, I don’t usually deal with any materials that would be considered very controversial. I research the way people (including students) write, read, speak and listen in situations related to science. When dealing with students, many of the activities that I use for research could also be used for educational purposes. For example, in a project this year I distributed different versions of scientific reading materials. I asked students to read these in pairs. I tape recorded their conversations and collected their written responses to the text. As a classroom teacher, these are strategies that I have used for educational purposes. Tape recording students allows me to listen to the struggles they might have had while reading a text. Collecting their written responses allows me to assess their understanding. Parents would not object to their child’s teacher using these tools for these purposes. When I visit a classroom as a researcher though, I am judged differently. Parents often do not consent to me collecting their children’s writing. They object, especially frequently, to my requests to videotape or photograph their children. This is because they rightfully understand educational research as a different activity from education. They use different judgments and expect different standards.

From the sequence of events, it sounds as if Berkeley admin started this project with their own perspective that this was clearly educational without adequate consideration that, from an outside position, it would be judged from a research perspective. I don’t want to suggest that this whole thing is a simple miscommunication because there are serious ethical implications related to asking for DNA samples. As people try to figure out how an educational idea ended up in the state legislature, though, I just wanted to add my perspective that some of the controversy might come from that shiver factor – something just doesn’t feel right. One aspect of that feel might be that this challenges the boundaries of our understanding of the activities of science and science education. The language and the tools and the objectives are mixed, leading to confusion about exactly what standards this should be judged against. As tools that have traditionally been associated with laboratory science become more accessible (as genetic testing is becoming) this boundary is likely to be challenged more and more. Those making the decisions to use these tools for educational, rather than research, purposes need to understand that challenging peoples conceptions of the boundaries between science and science education can and will lead to conflict and that conflict should be addressed head on and from the beginning.

The Benefits and Burdens of Genetic Testing

New podcast and forums at World Science: The Benefits and Burdens of Genetic Testing:

Listen to a story by reporter Marina Giovannelli, followed by our interview with Mayana Zatz.
Download MP3
Our guest in the Science Forum is geneticist and genetic counselor Mayana Zatz. She directs the Human Genome Research Center at the University of Sao Paolo.
Zatz has been working with patients with inherited disorders for nearly two decades. When it comes to genetic testing, Zatz advocates caution. Tests for some inherited disorders have helped people decide whether or not to have children. But in most cases, Zatz says genetic testing raises complex psychological and ethical issues:
* Should children be tested for late-onset disorders like Huntington’s disease and cerebellar ataxia? Doing so could lead to a life of dread, as they wait for a disease for which there is no cure.
* Interpreting the results from a genetic test can be difficult, especially for complex diseases like cancer or Alzheimer’s which are triggered by multiple factors, not just genetics.
Come join the conversation with Mayana Zatz. She’s taking your comments and questions through July 13th.
* Have you had your genes read? How did the results change your life?
* Should companies offering such tests be regulated?
* What kinds of medical benefits can we expect from genomics research in the coming years?

It’s not genetic (video)

Personalized Medicine: Too Much Information / Too Little Information

Next American Scientist Pizza Lunch:

It’s not often that we get to dive a little deeper into a topic encountered at a recent pizza lunch talk. But we will this month. In March, Geoff Ginsburg from Duke briefed us well on the current science regarding genomic (or personalized) medicine and its promising applications. At noon on Tuesday, April 20, Jim Evans from UNC-Chapel Hill will discuss the complexity of implementing this new medicine with a talk entitled: Personalized Medicine: Too Much Information / Too Little Information. Like Dr. Ginsburg, Dr. Evans is a doctor-scientist. He is also editor of the journal Genetics in Medicine and sits on an advisory committee to the U.S. Secretary of Health and Human Services on genetics, health and society.
American Scientist Pizza Lunch is free and open to science journalists and science communicators of all stripes. Feel free to forward this message to anyone who might want to attend. RSVPs are required (for the slice count) to
This time, we’ll be back at our home base, Sigma Xi in Research Triangle Park. You’ll find directions here:

American Scientist pizza lunch – genomic and personalized medicine

From the American Scientist:

Our American Scientist pizza lunch talk falls later than usual this month to accommodate our magazine’s May-June issue deadline. Keep open the noon hour on March 30 and come hear Geoff Ginsburg, director of the Center for Genomic Medicine at Duke University, discuss genomic and personalized medicine.
To keep you on your toes, we’ll convene at a different spot: the easy-to-get-to headquarters of the NC Biotechnology Center here in RTP. Actually, as many of you know, there would be no pizza lunch this year without the support of the Biotech Center. In addition to their financial help, center staff kindly offered to host one of our gatherings this year.
American Scientist Pizza Lunch is free and open to science journalists and science communicators of all stripes. Feel free to forward this message to anyone who might want to attend. RSVPs are required (for the slice count) to
Directions to the NC Biotechnology Center are here:

Can Genetically Engineered Crops Help Feed the World?

A new forum at World Science is up. As always, listen to the podcast first, then ask questions in the forum:

This week, India rejected what would have been the country’s first a genetically modified food crop, a transgenic eggplant.
The company that developed it, an Indian subsidiary of Monsanto, claims the crop would reduce pesticide use and boost yields. But the Indian government has decided to do independent assessments of the crop’s potential impacts on consumer health and the environment.
What does this mean for the future of GM crops in India and elsewhere? And does this technology have a role to play in feeding the world’s hungry?
We put these questions to Dr. Lisa Weasel. She’s a professor of biology at Portland State University, and the author of Food Fray: Inside the controversy of genetically modified food. She writes that GM crops are more of “a condiment than a main course” in solving the world’s food shortage.
Now it’s your turn to chat with Lisa Weasel. Join the conversation — it’s just to the right.
* Human beings have been altering plants ever since the beginning of agriculture. Why is genetic engineering any different from the older, more traditional ways of tinkering with crop varieties?
* Is there any scientific evidence of harm to human health from eating GM food?
* Why are small farmers in developing countries especially concerned about GM crops?

Science Cafe Raleigh: Dog Genome: Teaching Scientists New Tricks

Dog Genome: Teaching Scientists New Tricks
November 17th; 6:30-8:30 pm with discussion beginning at 7:00 followed by Q&A
The Irregardless Café, 901 W. Morgan Street, Raleigh 919.833.8898
This year, roughly 66,000 people will be diagnosed with non-Hodgkin lymphoma, while another 22,000 will be diagnosed with cancers of the brain. In parallel, our pet dogs also suffer from a range of similar spontaneous cancers. For thousands of years, humans and dogs have shared a unique bond–breathing the same air, drinking the same water, and living in the same environment. During the 21st century this relationship is now strengthened into one that may hold intriguing biomedical possibilities. Using the ‘One Medicine’ concept–the idea that human and animal health relies on a common pool of medical and scientific knowledge and is supported by overlapping technologies and discoveries; research is revealing that the dog genome may hold the keys to unlocking some of nature’s most intriguing puzzles about human cancer.
About the Speaker: Dr. Matthew Breen, professor of genomics in the NC State University College of Veterinary Medicine, co-directs the Clinical Genomics Core of the Center for Comparative Medicine and Translational Research at NC State. Dr. Breen’s lab helped map the canine genome in 2004 and the internationally known research scientist has conducted studies and published articles on numerous comparative medicine investigations of canine and human cancers including non-Hodgkin lymphoma, meningioma, and other cancers of the brain. A member of the Cancer Genetics Program at the University of North Carolina’s Lineberger Comprehensive Cancer Center, Dr. Breen’s collaborative investigations involve Duke University Medical Center and the University of Minnesota Medical Center among others.
RSVP:; or call 919-733-7450 ext 531

Hardware or Software: Searching for the Genetic Basis for Biological Diversity

Are you up to date on the hot debate in biology regarding how genes influence evolution? Some scientists contend genes are in the driver’s seat. Others assign more pull to regulatory factors controlling genetic expression. At noon, Wednesday, May 27, come hear Duke biologist Greg Wray explore the importance of it all in a talk entitled “Hardware or Software: Searching for the Genetic Basis for Biological Diversity.”
You may not want to miss this one. After Wray’s talk, Pizza Talk embarks on its traditional three-month summer vacation. The next nine-month series debuts in September.
Sigma Xi Pizza Lunch is free and open to science journalists and science communicators of all stripes. Feel free to forward this message to anyone who might be interested in attending. RSVPs are required (for a reliable slice count) to cclabby AT amsci DOT org.
Directions to Sigma XI:

Do you love or hate Cilantro?

If you think that political or religious debates can get nasty, you haven’t seen anything until you go online as see how much hate exists between people who love cilantro and those who hate cilantro. What horrible words they use to describe each other!!!!
Last weekend, I asked why is this and searched Twitter and FriendFeed for discussions, as well
Wikipedia and Google Scholar for information about it.
First – cilantro is the US name for the plant that is called coriander in the rest of the world. In the USA, only the seed is called coriander, and the rest of the plant is cilantro.
Second – there are definitely two populations of people: one (larger) group thinks that it is the best taste ever, while the other group thinks it is awful. The latter group is not simply incapable of tasting cilantro – they can taste it in minuscule quantities hidden in food and describe it as “dirty dish-soap water taste”. People who cannot stand cilantro leaf are perfectly OK with eating the coriander seed. So, it is something in the leaf that makes the difference.
Third – anecdotal information from scouring the Web suggests (“me and my Dad hate it…”) that the type of response to cilantro is inherited. It is also not experiental (those who hate it, hated it when they were kids, those who love it sometimes first tried it when they were already old and loved it at first try, and the response does not change with age, amount, kind of food preparation, etc).
Fourth – there is no scientific literature that I could find on the genetics of this. Is the difference at the level of the gustatory (or olfactory) receptors, or at higher-level processing centers in the brain?
Fifth – there is one paper that shows that the type of response to cilantro taste has nothing to do with the individual being a supertaster or not.
Sixth – There are a few older papers that identified chemical compounds in the leaves of cilantro, and a few about the allergy to cilantro, but no final identification of the compound that makes the difference in taste to the two groups.
So, does anyone else know more about this? Let us know in the comments.
In the meantime, be nice to people who are not your cilantro-type – they cannot help it.

From cloning to stem cells: How can pigs help us solve problems in human medicine?

From Sigma Xi:

NCSU molecular biologist Jorge Piedrahita has cloned pigs and explored why they are not carbon copies despite sharing the same DNA. Now he is trying to crack puzzles that could result in transgenic animals useful in human and veterinary medicine. His studies in cloned pigs led him to an unusual family of genes called imprinted genes, involved in placental function and fetal development. Recently he found they are implicated in human diseases too and is developing stem cell technologies in swine to try to speed up clinical applications in people.
To learn more, come hear Piedrahita discuss “From cloning to stem cells: How can pigs help us solve problems in human medicine?” at the next Sigma Xi Pizza Lunch at noon on Wednesday, March 25.
Pizza Lunch is free and open to science journalists and science communicators of all stripes. Feel free to forward this message to others you think might be interested. RSVPs are required (for a reliable slice count) to
Directions to Sigma XI:

Hope to see you there,

Science Cafe, Raleigh: Gene-Environment Interactions


Tuesday, March 24
6:30-8:30 pm
Science Cafe, Raleigh: Gene-Environment Interactions
EPA statistician and geneticist David Reif discusses the interplay between our genes and the environment. What does our shared evolutionary history have to do with common, complex diseases? How might genetics shape differential susceptibility to the multitude of chemicals–both manufactured and natural–present in the environment? How do modern lifestyles impact the evolutionary process? Tir Na Nog, 218 South Blount Street, Raleigh, NC, 919.833.7795

Meetings I’d like to go to….Part V

Genetic Manipulation of Pest Species: Ecological and Social Challenges:

In the past 10 years major advances have been made in our ability to build transgenic pest strains that are conditionally sterile, harbor selfish genetic elements, and express anti-pathogen genes. Strategies are being developed that involve release into the environment of transgenic pest strains with such characteristics. These releases could provide more environmentally benign pest management and save endangered species, but steps must be taken to insure that this is the case and that there are no significant health or environmental risks associated with releases. Our conference will foster discussion of risks and benefits of these technologies among scientists, policy makers, and citizens.

March 4-6, 2009
North Carolina State University, Raleigh, NC
This is very soon – I’ll try to go to some of it if I can….

Humanity’s Path (video)

This shows how waves of humans spread throughout the world from their origins in Africa over a period of some 50,000 years. The video was created by geneticist Daniel Falush of University College Cork in Ireland and colleagues. For more info, go here:
Soundtrack courtesy of Garageband

The map is in the bag, but the sequence may yet reveal if kangaroos have jumping genes

There is an utterly confusing press release out today – Australian First: Kangaroo Genome Mapped:

Australian researchers are launching the world first detailed map of the kangaroo genome, completing the first phase of the kangaroo genomics project.

Why is it confusing?
Because we are used to seeing press officers and media botch the terms. They often use the words “map” and “sequence” interchangeably.
Mapping a genome means locating genes on chromosomes, i.e., you get to know where each gene is on each chromosome. For this, you do not need to know the sequences of any genes, and certainly not the sequences of stuff between and around the genes.
Sequencing a genome means figuring out the exact order of all nucleotides in the entire DNA of the organism.
Some people do the mapping. Some do the sequencing. Some map first, sequence second. Others sequence first, map later. Some sequence most of the genome, then map it in order to put the last finishing touches on the sequencing, i.e., making sure that all the fragments are ordered correctly.
What appears that the Australian team did is that they mapped the Tammar Wallaby genome first. They intend to sequence it next year.
The source of confusion is the press release which does not state this clearly. Usually a press release reports on the research that is already done and published. In this case, the press release mixes together TWO statements – a) the map has been finished, and b) the sequence is on its way next year. The first is done, the second is yet to be done.
RPM and T. Ryan Gregory are trying to grapple with it all.

UNC scientists comment in support of fruit fly research for understanding autism

As a follow-up to the yesterday’s press release, Dr. Manzoor Bhat and Joseph Piven, M.D., researchers at the University of North Carolina in Chapel Hill who use the Drosophila model system to study neurexin and its implications in the development of autism, have now released the video response – well worth watching:

Wikipedia, just like an Organism: clock genes wiki pages

ResearchBlogging.orgThe October issue of the Journal of Biological Rhythms came in late last week – the only scientific journal I get in hard-copy these days. Along with several other interesting articles, one that immediately drew my attention was Clock Gene Wikis Available: Join the ‘Long Tail’ by John B. Hogenesch and Andrew I. Su (J Biol Rhythms 2008 23: 456-457.), especially since John Hogenesh and I talked about it in May at the SRBR meeting.
Now some of you may be quick to make a connection between this article and its author Andrew Su and A Gene Wiki for Community Annotation of Gene Function, published in PLoS Biology back in July, where one of the authors is also Andrew Su. And you would be right – it’s the same person and the two articles are quite related.
In the PLoS Biology article, they write:

A loose organization of Wikipedia editors has spearheaded the creation and expansion of several thousand articles related to molecular and cellular biology (the “MCB Wikiproject”), including many gene-specific pages. These articles vary widely in quality, format, and completeness, ranging from relatively complete encyclopedic entries (e.g., “enzyme,” “oxidative phosphorylation,” and “RNA interference”) to very short collections of information called “stubs” (e.g., “amphinase” and “glomus cell”). As an example of the collaborative writing process, the article on RNAi has been edited 708 times by 232 unique editors since its initial creation in October 2002. On the subject of human genes, generally only the most well-characterized of genes and proteins have highly developed entries (e.g., “HSP90″ and “NF- B”).
In principle, a comprehensive gene wiki could have naturally evolved out of the existing Wikipedia framework, and as described above, the beginnings of this process were already underway. However, we hypothesized that growth could be greatly accelerated by systematic creation of gene page stubs, each of which would contain a basal level of gene annotation harvested from authoritative sources. Here we describe an effort to automatically create such a foundation for a comprehensive gene wiki. Moreover, we demonstrate that this effort has begun the positive-feedback loop between readers, contributors, and page utility, which will promote its long-term success.

In the JBR paper, the authors focus on the development of Wikipedia pages describing genes involved in circadian rhythms, probably the first genes to be done comprehensively there, as an example for others as to how to do this kind of thing:

Why use Wikipedia for this? First, Google and Wikipedia have already become scientific research tools. When you Google an unfamiliar gene you usually end up at common sites of gene annotation such as the National Center for Biotechnology Information. Though these sites have expert curators who do the best they can, they are usually not domain experts and are so overloaded that they frequently fall behind in accurately summarizing the literature. (It’s actually amazing what they accomplish given available resources.) For confirmation, research your favorite gene. Using Wikipedia will allow our community to build and evolve living, up-to-date summaries on the function of important genes in the circadian network. Check out the pages on Arntl ( and Rev-erb-alpha ( Second, in part due to Wikipedia’s past success, its pages appear near the top of search engine lists such as Google, and consequently attract viewers. Finally, our field competes with other disciplines for the best and the brightest young scientists. These people use Wikipedia. High quality pages on annotated clock genes will attract their attention, and attract them to our field.

Importantly, the gene pages need not be extremely long. What is much more important is that they be well referenced. See, for instance Wikipedia pages they mention, those for ARNTL gene (also known as Bmal1 or Mop3), or Rev-ErbA alpha (I have written about some of these genes before, e.g., Lithium, Circadian Clocks and Bipolar Disorder, Tau Mutation in Context and The Lark-Mouse and the Prometheus-Mouse if you want more background). That is all that is needed – if I wanted to be silly, I could say that since genes are small, their wiki pages need to be small as well. But that is only half-silly, really.
This is just like in the real world. Genes don’t really do anything. They are coded descriptions of parts in a catalog. To explain a biological function, one needs to go from genes to their mRNAs to proteins, then to look at protein modifications and how multiple proteins interact with each other. Then see how such protein interactions affect the behavior of a cell. Then see how the altered behavior of a cell affects the entire tissue and how the changes in that tissue affect distant organs. Finally, one gets to explain the function once one understands how a collection of organs, interacting with the external environment, results in changes in biochemistry, development, physiology or behavior of the organism, and how this function evolved.
In the same way, gene pages on Wikipedia are not supposed to be stand-alone. Knowing everything about a clock gene does not mean one knows anything about circadian rhythm generation and modulation (not to mention its evolution). The value is in links – to all the other clock genes, to genes that do similar things (e.g., other transcription factors or nuclear receptors), to primary literature on the proteins coded by these genes and their interactions, and to higher-level functions, e.g., the Circadian Rhythms page and links within.
Some would ask – Why Wikipedia (I know, there are still some people out there who don’t like it):

What’s the downside? The major criticism is poor annotation. Actually, we argue that no annotation is worse than poor annotation, as the latter tends towards self-correction by provoking experts to intervene. In fact, a recent study concluded that Wikipedia was as accurate as Encyclopedia Britannica, and unlike Britannica, growing at a rate of 1500 articles per day (Giles, 2006). Another potential downside is non-consensual or controversial entries. We would argue that these are better addressed in real time via Wikipedia than in journal articles, where they remain fixed for years. Wikipedia even has tools to deal with controversial topics (for examples, see entries on “Intelligent Design,” evolution, “Swift-boating,” or climate change).

And, I’d argue, clock gene pages are not as contentious as those on climate change or creationism. Very few Wikipedia pages are so controversial as to be continuously suspect. Almost all of the pages are on non-controversial subjects, written and edited by experts on the topic, and are as reliable, or better, as anything else one can find out there, not to mention the fastest to get updated once new information comes in.
The effort is starting with the focus on mammalian genes, for obvious reasons of medical relevance and the existence of a wealth of information. But there is just as much, if not more, information on Drosophila clock genes. And comparative analysis of clock-genes in a variety of organisms is the key to understanding the circadian function and its evolution, so if your strength is in other old or emerging model organisms (did you see Japanese quail on that list?!), don’t hesitate to add the pages and information on those.
Finally, I’d like to urge you to contribute – I know that many chronobiologists read this blog (though most are silent types who never comment). It will take 30-60 minutes of your time to make or edit a page on the gene (or a higher-level process) in circadian biology and this effort will have much bigger audience and much broader impact than all of your peer-reviewed papers put together. It’s worth your time even if probably will have no effect on your getting tenure. But the tenure committee is not your only audience – there are researchers around the world (many in developing countries), teachers and students and lay audience, who will be affected by your contribution in a much more lasting and important ways than the inner circle of your department. Isn’t this why you are doing science in the first place?
If you want to discuss this more, come to ScienceOnline09, where John Hogenesh, one of the authors of the JBR article, will demonstrate Wiki Genes, answer questions, and deeply internalize your suggestions ;-)
John B. Hogenesch and Andrew I. Su, Clock Gene Wikis Available: Join the ‘Long Tail’, J Biol Rhythms 2008 23: 456-457.
Jon W. Huss, Camilo Orozco, James Goodale, Chunlei Wu, Serge Batalov, Tim J. Vickers, Faramarz Valafar, Andrew I. Su (2008). A Gene Wiki for Community Annotation of Gene Function PLoS Biology, 6 (7) DOI: 10.1371/journal.pbio.0060175

How to BLAST Sarah Palin

Jonathan describes, step by step.
I wonder if there are any palindromic sequences to be found?

Light-Responsive genes in rice

Friendly blogger Pamela Roland, the author of Tomorrow’s Table: Organic Farming, Genetics, and the Future of Food which I am reading right now (and which was recently reviewed in PLoS Biology), has just had a paper published in PLoS Genetics:
Identification and Functional Analysis of Light-Responsive Unique Genes and Gene Family Members in Rice

Rice, a model monocot, is the first crop plant to have its entire genome sequenced. Although genome-wide transcriptome analysis tools and genome-wide, gene-indexed mutant collections have been generated for rice, the functions of only a handful of rice genes have been revealed thus far. Functional genomics approaches to studying crop plants like rice are much more labor-intensive and difficult in terms of maintaining the plants than when studying Arabidopsis, a model dicot. Here, we describe an efficient method for dissecting gene function in rice and other crop plants. We identified light response-related phenotypes for ten genes, the functions for which were previously unknown in rice. We also carried out co-expression analysis of 72 genes involved in specific biochemical pathways connected in lines carrying mutations in these ten genes. This analysis led to the identification of a novel set of genes likely involved in these pathways. The rapid progress of functional genomics in crops will significantly contribute to overcoming a food crisis in the near future.

When science bloggers publish, then blog about it ;-)

On Tuesday night, when I posted my personal picks from this week’s crop of articles published in PLoS ONE, I omitted (due to a technical glitch on the site), to point out that a blog-friend of mine John Logsdon published his first PLoS ONE paper on that day:

It’s a updated and detailed report on the ongoing work in my lab to generate and curate an “inventory” of genes involved in meiosis that are present across major eukaryotic lineages. This paper focuses on the protist, Trichomonas vaginalis, an organism not known to have a sexual phase in its life cycle.

Here is the paper (and check John’s post for his experiences publishing in PLoS ONE):
An Expanded Inventory of Conserved Meiotic Genes Provides Evidence for Sex in Trichomonas vaginalis:

Meiosis is a defining feature of eukaryotes but its phylogenetic distribution has not been broadly determined, especially among eukaryotic microorganisms (i.e. protists)–which represent the majority of eukaryotic ‘supergroups’. We surveyed genomes of animals, fungi, plants and protists for meiotic genes, focusing on the evolutionarily divergent parasitic protist Trichomonas vaginalis. We identified homologs of 29 components of the meiotic recombination machinery, as well as the synaptonemal and meiotic sister chromatid cohesion complexes. T. vaginalis has orthologs of 27 of 29 meiotic genes, including eight of nine genes that encode meiosis-specific proteins in model organisms. Although meiosis has not been observed in T. vaginalis, our findings suggest it is either currently sexual or a recent asexual, consistent with observed, albeit unusual, sexual cycles in their distant parabasalid relatives, the hypermastigotes. T. vaginalis may use meiotic gene homologs to mediate homologous recombination and genetic exchange. Overall, this expanded inventory of meiotic genes forms a useful “meiosis detection toolkit”. Our analyses indicate that these meiotic genes arose, or were already present, early in eukaryotic evolution; thus, the eukaryotic cenancestor contained most or all components of this set and was likely capable of performing meiotic recombination using near-universal meiotic machinery.

Domestication – it’s a matter of time (always is for me, that’s my ‘hammer’ for all nails)

Since this article came out in The American Scientist (the only pop-sci magazine that IMHO has not gone downhill in quality over the past decade) in early 1999 (you can read the entire thing here (pdf)) I have read it many times, I used it in teaching, I discussed it in Journal Clubs, and it is a never-ending fascination for me. Now Andrew and Greg point out there is YouTube video about the fox domestication project:

Back in the 1950s, Dmitri Konstantinovich Belyaev started an experiment in which he selectively bred Silver Foxes, very carefully, ONLY for their tameness (and “tameness” was defined very rigorously in terms of type and speed of response, distance that triggers aggression, etc.).
What happened really fast in this experiment is that many other traits showed up, seemingly out of nowhere, in the subsequent generations. They started having splotched and piebald coloration of their coats, floppy ears, white tips of their tails and paws. Their body proportions changed. They started barking. They improved on their performance in cognitive experiments. They started breeding earlier in spring, and many of them started breeding twice a year.
Most of the people reacting to this experiment invoked pleiotropy, i.e., how changes in one gene affect expression of many other genes. See this NYT article for instance. However, even while I was reading it for the first time, my mind screamed – development! And not just development, but more specifically, heterochrony – change in timing of developmental event.
If you alter the expression of one of the genes that affects developmental timing, you affect all sorts of things.
For instance, when the neural crest cells migrate they become melanocytes in the skin – if due to changes in timing they are late to arrive to some distal parts, e.g., paws and tail-tips, those part will be white. Neural crest cells also migrate to become the adrenal medulla – that little part of the body that releases (nor)epinephrine (adrenaline). If fewer of those cells arrive there on time, less the animal will show stress-response later in life.
There appears to be tight correlation between timers that act on different scales, e.g., developmental and circadian timing, circadian and fast behavioral timing, circadian and seasonal timing, etc.
I always wished I could get a lab, some foxes, an IACUC approval and some money to run these animals through a battery of standard experiments comparing dogs, wild foxes and domesticated foxes on all sorts of parameters of circadian rhythms, photoperiodism (they did change their seasonality patterns of breeding, after all), etc.
The bottom line is that a subtle change in timing of expression of a single developmental gene, something one can select for by choosing one of the traits (in this case a behavioral trait), will affect the change in timing of expression in many other genes. The difference between wild and domesticated foxes may not be in any DNA sequence at all – it could presumably be all epigenetic (see also). Sequence differences would arise later, as the two populations are not inter-mixing any more (for 60 years now).
When you put together development, genetics and evolution, you can see that big changes (or, really, any changes at the very beginning of the evolutionary change) in DNA sequence are not necessary for big changes in entire suites of phenotypic traits. But in the 1950s, the bean-bag deterministic genetics was the norm, so the Belyaev experiment was a big jolt to the scientific community in the West (not so much for the Russian evolutionary biologists, though), so we need to look at this experiment through a decent grasp of history.
Now, I’d like to know what is the state of the experiment today. Ten years ago, the project appeared doomed – they had to sell foxes for fur in order to keep going at a small scale. Has this been fixed? Has anyone from the West help finance the continuation of the project? Has anyone in the West acquired some of the foxes and continued with the project? What are the recent developments?

Happy birthday, PLoS Genetics!

PLoS Genetics is celebrating its third birthday this month! Let’s see what’s new this week, among else…
PLoS Genetics Turns Three: Looking Back, Looking Ahead:

PLoS Genetics is three years old this month–a milestone worth celebrating! As we do, and as we recognize all who have helped us reach this point in time, we thought this would be a good opportunity to share with you a summary of our brief history and a look ahead.
Our original intent was to provide an open-access journal for the community that would “reflect the full breadth and interdisciplinary nature of genetics and genomics research by publishing outstanding original contributions in all areas of biology.” Now, three years later, all of us on the Editorial Board are very pleased with the breadth of topics covered and with the diversity of approaches, organisms, and systems. Going forward, PLoS Genetics will continue to be a journal by and for the entire genetics and genomics community.

The Status of Dosage Compensation in the Multiple X Chromosomes of the Platypus:

Dosage compensation equalizes the expression of genes found on sex chromosomes so that they are equally expressed in females and males. In placental and marsupial mammals, this is accomplished by silencing one of the two X chromosomes in female cells. In birds, dosage compensation seems not to be strictly required to balance the expression of most genes on the Z chromosome between ZZ males and ZW females. Whether dosage compensation exists in the third group of mammals, the egg-laying monotremes, is of considerable interest, particularly since the platypus has five different X and five different Y chromosomes. As part of the platypus genome project, genes have now been assigned to four of the five X chromosomes. We have shown that there is some evidence for dosage compensation, but it is variable between genes. Most interesting are our results showing that there is a difference in the probability of expression for X-specific genes, with about 50% of female cells having two active copies of an X gene while the remainder have only one. This means that, although the platypus has the variable compensation characteristic of birds, it also has some level of inactivation, which is characteristic of dosage compensation in other mammals.

Pain Genes:

Pain, which afflicts up to 20% of the population at any time, provides both a massive therapeutic challenge and a route to understanding mechanisms in the nervous system. Specialised sensory neurons (nociceptors) signal the existence of tissue damage to the central nervous system (CNS), where pain is represented in a complex matrix involving many CNS structures. Genetic approaches to investigating pain pathways using model organisms have identified the molecular nature of the transducers, regulatory mechanisms involved in changing neuronal activity, as well as the critical role of immune system cells in driving pain pathways. In man, mapping of human pain mutants as well as twin studies and association studies of altered pain behaviour have identified important regulators of the pain system. In turn, new drug targets for chronic pain treatment have been validated in transgenic mouse studies. Thus, genetic studies of pain pathways have complemented the traditional neuroscience approaches of electrophysiology and pharmacology to give us fresh insights into the molecular basis of pain perception.

Stable in a Genome of Instability: An Interview with Evan Eichler:

We like to think that our genome is rock-solid, that it is dependable, there for us when we need it. The truth is far from that. By fits and starts, our species’ collective genome is undulating, reshaping itself with eruptions of genomic lava and clashes of sequence tectonics, at once both marvelous and unsettling. We are unaware of this tumult within us until we are confronted with disease in ourselves, our friends, or our family.
Evan Eichler is a man obsessed with this process, and to speak with him is a study in contrasts (Image 1). An unassuming Canadian, Eichler is a student of genomic architecture, the arrangement of sequences in our genome, and their evolution. Eichler grew up on a farm in Manitoba, married his college sweetheart, and now lives together with her and their four children in the mountains east of Seattle. As we walked up the hill to my office during his recent visit to UCSF, he talked about being an early riser, taking his son to band practice before school, and then driving the 30 miles to work in his Toyota. Eichler is a man bristling with excitement for his discoveries, but holding it in check by a tradition of modesty. He has consistently followed his own path, chosen career opportunities that were dictated not by politics or peer pressure but rather by what feels like a good fit for him.

Chatting about Epigenetics

Abbie and PZ chat about the recent discoveries in biology, how exciting those discoveries are, and how annoying it is when Creationists try to put a damper on such excitement:

Using DNA barcoding to identify illegal bushmeat jerky trade

This is very cool – African Bushmeat Expedition is a project which takes high school students to Africa where they both learn the techniques and at the same time do something very useful – track the appearance of wild animal meat in the market:

Although illegal wildlife poaching is conducted worldwide, the impact in Africa has been devastating. Unsustainable commercial hunting for bushmeat will inevitably lead to species extinction. In turn, localized species extinction impacts the health of native ecosystems. Marketing of illegal bushmeat can also have serious ramifications because pathogens present in the meat may be transmitted, through ingestion, to the human population. The DNA barcoding technique implemented by High Tech High students will provide a useful tool for environmental impact studies by allowing scientists and environmental groups to trace illegal bushmeat back to its localized animal populations.

What is it all about?

In 2005, Jay Vavra of High Tech High in San Diego and Oliver Ryder of the San Diego Zoological Society collaborated to create a conservation forensics course, instructing HTH students on species identification via DNA barcoding. Students studied African bushmeat trade and focused on identification of simulated bushmeat samples, using jerky from a range of species for the process. Advanced studies included experimental methods of DNA extraction and amplification as well as alternative means of DNA preservation for shipment of DNA from Africa. The next step in the study is establishing partnerships and education programs at Mweka College and other sites by bringing students to East Africa to build this novel conservation education program in Africa and to disseminate instructional material in the United States.

The expedition just ended and the participants blogged the expedition and their experiences – check out the blog here.

The assembly was greatly interested in and impressed with our work, and the meeting was a great success. It was fantastic to bring together all that we had learned in the classroom the past few years and in the field the past few weeks.

Do judges need to know their Genetics?

Jim Evans, my friend here at UNC, says Yes, in an interview with NYTimes, and again on NPR’s People’s Pharmacy. He teaches a course on genetics to judges:

A lot of judges report that they did prelaw in college because it did not involve science. One of my favorite judges, a brilliant man, is fond of telling people he “flunked science in kindergarten.” So in these workshops, I think of myself as a newfangled type of science teacher, instructing extremely smart and distinguished adults in science fundamentals.

A cellular riddle

It takes 38 minutes for the E.coli genome to replicate. Yet, E.coli can bo coaxed to divide in a much shorter time: 20 minutes. How is this possible?
Larry poses the riddle and provides the solution.
The key is that complex biochemical processes are taught sequentially, one by one, because that is how we think and process information. Yet, unless there is a need for precise timing (in which case there will be a timer triggering the starts and ends of cellular events), most processes occur all the time, simultaneously, in parallel. How do we teach that?

Yay for Platypus!

The genome of the Platypus has been sequenced:

The first analysis of the genome sequence of the duck-billed platypus was published today by an international team of scientists, revealing clues about how genomes were organized during the early evolution of mammals. The research was supported in part by the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH).
Fans of TV nature shows will remember that the duck-billed platypus, native to Australia, is one of the few mammals that lay eggs. However, platypus peculiarity does not end there. For example, these odd animals boast what looks like a duck’s bill, which houses an electrosensory system used when foraging for food underwater, and a thick fur coat to adapt to the icy waters in which it resides. Males also possess hind leg spurs that can deliver venom powerful enough to wound territorial competitors during mating season, or cause excruciating pain in other mammals, including humans.
“At first glance, the platypus appears as if it was the result of an evolutionary accident. But as weird as this animal looks, its genome sequence is priceless for understanding how fundamental mammalian biological processes have evolved,” said Francis S. Collins, M.D., Ph.D., director of NHGRI. “Comparisons of the platypus genome to those of other mammals will provide new insights into the history, structure and function of our own genome.”
In a paper published in today’s issue of the journal Nature, researchers analyzed a high-quality draft genome sequence of Glennie, a female platypus from Australia. The consortium included scientists from the United States, Australia, England, Germany, Israel, Japan, New Zealand and Spain. Sequencing of the platypus genome was led by the Genome Sequencing Center at Washington University School of Medicine in St. Louis, a part of NHGRI’s Large-Scale Sequencing Research Network.
Once the sequence was produced, researchers began comparing the genome of the platypus, whose ancestors split from the rest of mammalian lineage some 166 million years ago, with the well-characterized genomes of the human, mouse, dog, opossum and chicken, as well as the draft genome sequence of the green anole lizard. The chicken genome was chosen because it is descended from the ancestral group of egg-laying animals, including extinct reptiles, who passed on much of their DNA to animals like the platypus. Scientists were particularly interested in finding features within the platypus genome that could explain the odd mix of characteristics seen in the platypus: those that were more like reptiles, birds and mammals.
The team found that the platypus genome contains about the same number of protein-coding genes as other mammals — approximately 18,500. The platypus also shares more than 80 percent of its genes with other mammals whose genomes have been sequenced. Next, researchers combed the platypus genome looking for genetic evidence of sequences unique to platypuses that have been lost from mammalian genomes. Scientists were also eager to find out what characteristics of the platypus were linked at the DNA level to reptiles or mammals.
“The mix of reptilian, mammalian and unique characteristics of the platypus genome provides many clues to the function and evolution of all mammalian genomes,” said Richard K. Wilson, Ph.D., director of Washington University School of Medicine’s Genome Sequencing Center and the paper’s senior author. “Now, we’ll be able to pinpoint genes that have been conserved throughout evolution, as well as those that have been lost or gained.”

Read the rest here and the Nature article here

Microbial genomics in PLoS

Considering this I am kinda baffled by this. There is tons of microbial metagenomics and genomics in PLoS journals.

Interview with Svante Paabo

Imagine: An Interview with Svante Paabo:

Svante Paabo works on the edge of what’s possible. He ignites our imagination, unlocking tightly held secrets in ancient remains. By patiently and meticulously working out techniques to extract genetic information from skin, teeth, bones, and excrement, Paabo has become the leader of the ancient DNA pack. Sloths, cave bears, moas, wooly mammoths, extinct bees, and Neanderthals–all have succumbed to his scrutiny.
Paabo (see Image 1) broke ground in 1985, working surreptitiously at night in the lab where he conducted his unrelated PhD research, to extract, clone, and sequence DNA from an Egyptian mummy.

Genomics Blogger Dissed by the New York Times

Or, perhaps, the truth is more complicated, as revealed in the comments of that post.

Congratulations to Karen James!

Excitement on science blogs! Karen James of the Beagle Project Blog has just today published a paper in PLoS ONE:
Diversity Arrays Technology (DArT) for Pan-Genomic Evolutionary Studies of Non-Model Organisms:

High-throughput tools for pan-genomic study, especially the DNA microarray platform, have sparked a remarkable increase in data production and enabled a shift in the scale at which biological investigation is possible. The use of microarrays to examine evolutionary relationships and processes, however, is predominantly restricted to model or near-model organisms.
Methodology/Principal Findings
This study explores the utility of Diversity Arrays Technology (DArT) in evolutionary studies of non-model organisms. DArT is a hybridization-based genotyping method that uses microarray technology to identify and type DNA polymorphism. Theoretically applicable to any organism (even one for which no prior genetic data are available), DArT has not yet been explored in exclusively wild sample sets, nor extensively examined in a phylogenetic framework. DArT recovered 1349 markers of largely low copy-number loci in two lineages of seed-free land plants: the diploid fern Asplenium viride and the haploid moss Garovaglia elegans. Direct sequencing of 148 of these DArT markers identified 30 putative loci including four routinely sequenced for evolutionary studies in plants. Phylogenetic analyses of DArT genotypes reveal phylogeographic and substrate specificity patterns in A. viride, a lack of phylogeographic pattern in Australian G. elegans, and additive variation in hybrid or mixed samples.
These results enable methodological recommendations including procedures for detecting and analysing DArT markers tailored specifically to evolutionary investigations and practical factors informing the decision to use DArT, and raise evolutionary hypotheses concerning substrate specificity and biogeographic patterns. Thus DArT is a demonstrably valuable addition to the set of existing molecular approaches used to infer biological phenomena such as adaptive radiations, population dynamics, hybridization, introgression, ecological differentiation and phylogeography.

Have no idea what it all means? Be patient. Karen will explain it all on the Beagle Project Blog in a day or two….

Viruses in the Oceans: join the latest Journal Club

Brendan Bohannan, Richard W. Castenholz, Jessica Green and their students and postdcos at the Center for Ecology and Evolutionary Biology at University of Oregon are currently doing a Journal Club on the PLoS ONE article The Sorcerer II Global Ocean Sampling Expedition: Metagenomic Characterization of Viruses within Aquatic Microbial Samples, which is part of the PLoS Global Ocean Sampling Collection. Please join in the discussion.

DNA barcoding

I tried to understand what DNA barcoding is, as everyone is talking about it. And I tried reading a couple of papers about it – I am a biologist, so I should have understood them, but nope, I was still in the dark.
So, what does one do? Waits for a science blogger to explain it. And so it happens, Karen explained it yesterday. I read it. Slowly and carefully. Only once. And I grokked it all!

Intelligently Designed DNA

Someone did it.
Get a prize if you correctly identify which one is intelligently designed.
In both cases, the designer was an intelligent…..human. Of course. No media reports yet of bioengineering labs run by chimps, dogs, elephants or dolphins.

The Hopeless Monster? Not so fast!

Olivia Judson wrote a blog post on her NYTimes blog that has many people rattled. Why? Because she used the term “Hopeful Monster” and this term makes many biologists go berserk, foaming at the mouth. And they will not, with their eye-sight fogged by rage, notice her disclaimer:

Note, however, that few modern biologists use the term. Instead, most people speak of large morphological changes due to mutations acting on single genes that influence embryonic development.

So, was Olivia Judson right or wrong in her article? Both. Essentially she is correct, but she picked some bad examples, overgeneralized a bit, over-reached a little and she used the dreaded term that was bound to shut down all rational processes occurring in some biologists’ brains. Remember that she wrote to general audience. If she took time and space to explain all the nuances and details she would have lost her audience somewhere in the middle of the second paragraph. I think that her post explains the topic just fine for the intended audience, pointing out that not all evolutionary changes take millions of years of imperceptible change – some do, indeed, happen relatively abruptly (yet it can be explained completely mechanistically, not giving Cdesign Proponentsists any hope). Not every day, but they do.
So, who jumps first into the fray with an angry rebuttal – one of the Usual Suspects: Jerry Coyne in a guest-post on The Loom:

Unfortunately, her piece is inaccurate and irresponsible, especially for a journalist with a strong science background (Judson has a doctorate from Oxford). I’ve admired Judson’s columns and her whimsical and informative book Dr. Tatiana’s Sex Advice to All Creation. But this latest posting is simply silly. As an evolutionary biologist, I’m used to seeing our field twisted out of shape to satisfy the demands of journalists who love sensational new findings–especially if they go against long-held Darwinian beliefs like the primacy of gradual, stepwise evolution. But I’m not used to seeing one of my own colleagues whip up excitement about evolutionary biology by distorting its findings.

Unfortunately, in bashing Judson along with making legitimate points (how many people will ignore this caveat in their responses?), Coyne ends up being more wrong than she is. And his intended audience is, arguably, better scientifically educated than hers – it’s the readers, not NYTimes. While bashing her head into a rock, Jerry makes visible his emotional enmity towards everybody who has a bigger picture of evolution than he has and has at their disposal both a methodological and a conceptual toolkit that Jerry lacks.
Before you jump on me, read the historical reviews of the concept of the Hopeful Monster by Brian and John. Then, read Greg and Razib who are far too lenient on Coyne but add good points of their own. Finally, read PZ Myers and especially Larry Moran for a clear explanation of the entire set of issues – the history, sources of current emotional disputes, and the current science. Reading all of these is essential to understanding the claims in this post as I do not have space/time to repeat all of their claims at length – so click on the links and read first before commenting.
In a back-and-forth with a commenter, Coyne defends himself that he is talking about the changes in genes, not evolution. This just shows his bias – he truly believes that evolution – all of it – can be explained entirely by genetics, particularly population genetics. His preferred definition of evolution is probably the genocentric nonsense like “evolution is a change of gene frequencies in a population over time”. I prefer to think of it as “evolution is change in development due to ecology” (a softening of Van Valen’s overly-strong definition “evolution is control of development by ecology”). Population genetics is based on the Hardy-Weinberg equilibrium – pretty much all of it is a build-on and embellishment of it. Population geneticists tend to forget, once they get into complex derivations of HW, that HW has about a dozen completely unrealistic assumptions underlying it. Now, in a case-to-case basis, some of those assumptions can be safely ignored, some can be mathematically taken care of, but some are outside of the scope of mathematics (or at least the kind of math that can be integrated into the development of HW). Those are ignored or dismissed and, if this is pointed out by those working on evolution from a Bigger Picture perspective, met with anger.
When Goldshmidt’s book The Material Basis of Evolution was reissued, Stephen Jay Gould wrote a lengthy Introduction. About a dozen years ago I checked the book out of the library and skimmed the book itself. I read Gould’s intro very carefully (I wonder if it is available somewhere online for free? Update: Gould’s introduction is available online here, hat-tip to Michael Barton.). It is also worthwhile to read Gould’s 1980 essay The Return of Hopeful Monsters keeping in mind that evo-devo was barely beginning at the time (yes, it is 28 years old, so do not judge it by current knowledge – put a historian’s cap on when reading it).
In his Big Book, Gould wrote:

“By proposing a comprehensive formalist theory in the heyday of developing Darwinian orthodoxy, Richard Goldschmidt became the whipping boy of the Modern Synthesis–and for entirely understandable reasons. Goldschmidt showed his grasp, and his keen ability to utilize, microevolutionary theory by supporting this approach and philosophy in his work on variation and intraspecific evolution within the gypsy moth, Lymantria dispar. But he then expressed his apostasy by advocating discontinuity of causality, and proposing a largely nonselectionist and formalist account for macroevolution from the origin of species to higher levels of phyletic pattern. Goldschmidt integrated both themes of saltation (in his concept of “systemic mutation” based on his increasingly lonely, and ultimately indefensible, battle to deny the corpuscular gene) and channeling (in his more famous, if ridiculed, idea of “hopeful monsters,” or macromutants channeled along viable lines set by internal pathways of ontogeny, sexual differences, etc.). The developmental theme of the “hopeful monster” (despite its inappropriate name, virtually guaranteed to inspire ridicule and opposition), based on the important concept of “rate genes,” came first in Goldschmidt’s thought, and always occupied more of his attention and research. Unfortunately, he bound this interesting challenge from development, a partially valid concept that could have been incorporated into a Darwinian framework as an auxiliary hypothesis (and now has been accepted, to a large extent, if under different names), to his truly oppositional and ultimately incorrect theory of systemic mutation, therefore winning anathema for his entire system. Goldschmidt may have acted as the architect of his own undoing, but much of his work should evoke sympathetic attention today.”

So, Coyne’s Gould-bashing, as Larry Moran demonstrated, is just petty and baseless sniping by one scientist of limited scope at another who actually “got it”.
I thought the discussion so far has been far too tame. So, here is the red meat! I want to see a real fight – a blogospheric war that brings in some serious traffic, OK?

Clocks and Migratory Orientation in Monarch Butterflies

Blogging on Peer-Reviewed Research

I had no time to read this in detail and write a really decent overview here, perhaps I will do it later, but for now, here are the links and key excerpts from a pair of exciting new papers in PLoS Biology and PLoS ONE, which describe the patterns of expression of a second type of cryptochrome gene in Monarch butterflies.
This cryptochrome (Cry) is more similar to the vertebrate Cry than the insect Cry, also present in this butterfly. The temporal and spatial patterns of expression of the two types of Cry suggest that they may be involved in the transfer of time-information from the circadian clock to the brain center involved in spatial orientation during long-distance migration.
The PLoS Biology paper looks at these patterns of expression, while the PLoS ONE paper identifies a whole host of genes potentially implicated in migratory behavior, including the Cry2. Here is the PLoS Biology paper:
Cryptochromes Define a Novel Circadian Clock Mechanism in Monarch Butterflies That May Underlie Sun Compass Navigation:

During their spectacular fall migration, eastern North American monarch butterflies (Danaus plexippus) use a time-compensated sun compass to help them navigate to their overwintering sites in central Mexico. The circadian clock plays a critical role in monarch butterfly migration by providing the timing component to time-compensated sun compass orientation. Here we characterize a novel molecular clock mechanism in monarchs by focusing on the functions of two CRYPTOCHROME (CRY) proteins. In the monarch clock, CRY1, a Drosophila-like protein, functions as a blue-light photoreceptor for photic entrainment, whereas CRY2, a vertebrate-like protein, functions within the clockwork as the major transcriptional repressor of the self-sustaining feedback loop. An oscillating CRY2-positive neural pathway was also discovered in the monarch brain that may communicate circadian information directly from the circadian clock to the central complex, which is the likely site of the sun compass. The monarch clock may be the prototype of a clock mechanism shared by other invertebrates that express both CRY proteins, and its elucidation will help crack the code of sun compass orientation.

Here is the editorial synopsis:
In Monarchs, Cry2 Is King of the Clock:

Back in the brain, the authors showed that Cry2 was also found in a few dozen cells in brain regions previously linked to time-keeping in the butterfly, and this Cry2 underwent circadian oscillation in these cells, but not in many other cells that were not involved in time keeping. By taking samples periodically over many hours, they found that nuclear localization of Cry2 coincided with maximal transcriptional repression of the clockwork, in keeping with its central role of regulating the feedback cycle. This is a novel demonstration of nuclear translocation of a clock protein outside flies.
Finally, the authors investigated Cry2′s activity in the central complex, the brain structure that is believed to house the navigational compass of the monarch. Monarchs integrate information on the position of the sun and the direction of polarized light to find their way from all over North America to the Mexican highlands, where they spend the winter. Cry2, but not the other clock proteins, was detected in parts of the central complex where it undergoes strong circadian cycling. Some cells containing Cry2 linked up with the clock cells, while others projected toward the optic lobe and elsewhere in the brain.
Along with highlighting the central importance of Cry2 in the inner workings of the monarch’s clock, the results in this study suggest that part of the remarkable navigational ability of the butterfly relies on its ability to integrate temporal information from the clock with spatial information from its visual system. This allows the monarch to correct its course as light shifts across the sky over the course of the day. Other cues used for charting its path remain to be elucidated.

This is the PLoS ONE paper:
Chasing Migration Genes: A Brain Expressed Sequence Tag Resource for Summer and Migratory Monarch Butterflies (Danaus plexippus):

North American monarch butterflies (Danaus plexippus) undergo a spectacular fall migration. In contrast to summer butterflies, migrants are juvenile hormone (JH) deficient, which leads to reproductive diapause and increased longevity. Migrants also utilize time-compensated sun compass orientation to help them navigate to their overwintering grounds. Here, we describe a brain expressed sequence tag (EST) resource to identify genes involved in migratory behaviors. A brain EST library was constructed from summer and migrating butterflies. Of 9,484 unique sequences, 6068 had positive hits with the non-redundant protein database; the EST database likely represents ~52% of the gene-encoding potential of the monarch genome. The brain transcriptome was cataloged using Gene Ontology and compared to Drosophila. Monarch genes were well represented, including those implicated in behavior. Three genes involved in increased JH activity (allatotropin, juvenile hormone acid methyltransfersase, and takeout) were upregulated in summer butterflies, compared to migrants. The locomotion-relevant turtle gene was marginally upregulated in migrants, while the foraging and single-minded genes were not differentially regulated. Many of the genes important for the monarch circadian clock mechanism (involved in sun compass orientation) were in the EST resource, including the newly identified cryptochrome 2. The EST database also revealed a novel Na+/K+ ATPase allele predicted to be more resistant to the toxic effects of milkweed than that reported previously. Potential genetic markers were identified from 3,486 EST contigs and included 1599 double-hit single nucleotide polymorphisms (SNPs) and 98 microsatellite polymorphisms. These data provide a template of the brain transcriptome for the monarch butterfly. Our “snap-shot” analysis of the differential regulation of candidate genes between summer and migratory butterflies suggests that unbiased, comprehensive transcriptional profiling will inform the molecular basis of migration. The identified SNPs and microsatellite polymorphisms can be used as genetic markers to address questions of population and subspecies structure.

Here is an article written after the press release, which, as such articles usually do, greatly overstates the extent of the findings:
Clocking monarch migration:

In previous work, Reppert and his team showed that pigment-producing genes in the monarch eye communicate with the butterfly’s circadian clock. As part of the new study, Reppert and his team also found, in an area of the monarch brain called the central complex, a definitive molecular and cellular link between the circadian clock and the monarch’s ability to navigate using the sun. Briscoe said that Reppert’s study was “really going to overturn a lot of views we had about the specific components of circadian clocks.”

The spatial and temporal patterns of expression make Cry2 the most serious candidate for the connection between the clock and the Sun-compass orientation mechanism. Much work, both at the molecular and at higher levels of organization needs to be done to figure out the exact mechanism by which this animal, during migration, compensates for the Sun’s movement across the sky during the day, and thus does not stray off course. Cry2 appears to be a good molecular “handle” for such studies.
For background, see my older post on the initial discovery of Cry2 in Monarch butterflies by the same team.

Grapevine Genomes

Two grape genomes were published this year, one in Nature, the other in PLoS ONE. Larry Moran explains the methodologies and results of both and discusses the trustworthiness of each. The Nature paper is explained in The Grapevine Genome, and the PLoS ONE paper is discussed in The Second Grapevine Genome Is Published. Obligatory Readings of the Day.

Has the word “gene” outlived its usefulness?

Blogging on Peer-Reviewed Research

When Wilhelm Johannsen coined the word “gene” back in 1909 (hmmm, less than two years until the Centennial), the word was quite unambiguous – it meant “a unit of heredity”. Its material basis, while widely speculated on, was immaterial for its usefulness as a concept. It could have been tiny little Martians inside the cells, it would have been OK, as they could have been plugged into the growing body of mathematics describing the changes and properties of genes in populations. In other words, gene referred to a concept that can be mathematically and experimentally studied without a reference to any molecules or intracellular processes.
Fast-forward half a century to the discovery of DNA and subsequent discoveries of the genetic code, transcription, translation, various types of gene regulation, etc. Everyone was happy – finally, we had a material gene. We had a molecule of inheritance that we could study. And an army of thousands started studying it, announcing breakthroughs at a breath-taking pace.
The confusion about the use of the term ‘gene’, as everyone used it differently, grew over the years. The use of terminology from information theory (e.g., program, transcription, translation, algorithm) affected the way researchers thought and designed experiments, limiting for a long time all discourse on inheritance to just DNA and worse, just to the DNA sequence.
But research went on, hit the walls, and smart people found the ways around the conundrum. What the research uncovered undermined the “gene” as a unit of inheritance, and for that matter undermined DNA as the molecule of inheritance. What we have learned is that:
- there is a difference between what an organism gets from parents (a static concept of the gene) and what it does with it to properly develop, function and behave in a species-specific way (a dynamic concept of the gene)
- the DNA sequence is just one of many properties of DNA that is important for proper development, function and behavior of an organism – there are other properties of DNA, as well as other non-DNA factors that are equally important.
- a sequence of nucleotides that gets transcribed is a very poor definition of a gene, as so much happens between transcription and the generation of the final protein shape, not to mention the complexity of the question how a single protein contributes to the appearance of a phenotypic trait.
- DNA is not the only “thing” that an organism gets from the parents. There is also a DNA methylation pattern, the transcription/translation machinery of the egg cell, various molecules (RNA, proteins, steroid hormones, etc.) present in the egg cell or introduced by the sperm cell, the environment inside the egg or womb, and the external environment into which the parents deposit the progeny (including the special case of teaching/learning).
I have thought about this quite a lot over the years (see, for instance this, this, this, this and this) and more I thought about it, more I liked the ideas that Developmental Systems Theory had to offer. Last ten years of published research changed the way we think about this and changed my mind in many ways. In a way, I was right all along – it’s not just DNA that confers heredity (static concept of the gene). In other cases, I was wrong: it turned out that it is, in fact, DNA, just not its sequence, that does this or that job in running the organism (the dynamic concept of the gene).
Two of the books I have read over the years that tackled the problem in a very good way (though sometimes not going far enough for my own tastes) are Refiguring Life and The Century of the Gene by Evelyn Fox Keller, one of the most prominent thinkers about the problem right now.
Thus, I got really excited when I heard that Chris Surridge, editor of PLoS ONE, after mulling over it for a long time (philosophy of science is not supposed to be one of the topics ONE publishes papers on, at least officially and at least until now), decided to go with the reviewers’ recommendations and publish a paper by Evelyn Fox Keller and David Harel – Beyond the Gene – in which the concept of the gene is discussed. What the paper does, on top of coming up with concepts that clearly differentiate between the static and the dynamic meanings and incorporate the current understanding of the complexity of both, is propose new names for those concepts. Read it carefully – it is quite thought-provoking.
Proposing new terminology is easy. Having it accepted and used by others is far more difficult. Especially when the terms are picked very cleverly to pick up on particular mental associations, while at the same time being (probably intentionally) catchy and funny (if you read them out loud they sound like deans, beans and janitors). The straight-laced researchers will probably balk at the new words. The folks that give funny names to Drosophila genes (e.g., Sonic hedgehog or fruity…er, fruitless) will probably grok why these new proposed terms are potentially useful.
Just like their conception of gene in everyday work differs, I expect that the response to this article’s proposal will differ between a biochemist, a bioinformatics scientist, a biological anthropologist, a medical researcher and a developmental biologist, between someone who works on microbial genomes, or mammalian genetics, or compares all genomes or looks at the way viral and mammalian genomes interract, or someone who looks at evolution of genes, or population genetics, history of biology or philosophy of biology. I hope they and others chime in.

Meet Fred Gould (sans mosquitoes) over pizza

Another thing I will also have to miss – the Inaugural Event of the 2007-2008 Pizza Lunch Season of the Science Communicators of North Carolina (SCONC), on October 24th at Sigma Xi Center (the same place where we’ll have the Science Blogging Conference). Organized by The American Scientist and the Burroughs Wellcome Fund, the first Pizza Lunch Session will feature Dr.Fred Gould, professor of Entomology and Genetics at NCSU (whose Insect Ecology class blows one’s mind – one of the best courses I have ever taken in my life). Fred recently received The George Bugliarello Prize for an interdisciplinary article Genetic Strategies for Controlling Mosquito-Borne Diseases. You can read an article about him in Raleigh News and Observer or, even better, listen to him on this podcast on State Of Things a few weeks ago. Notice with what disdain he utters the term “junk DNA” – only once in the entire hour – in order to explain it (away).

Genes vs./plus Environment

My former SciBling David Dobbs regularly posts on the SciAm Blog, usually bringing in guest contributors highlighting novel research in neuroscience. Today, he invited Charles Glatt to review an interesting study on the interaction between genes and environment in development of depression. David writes:

This week reviewer Charles Glatt reviews a study that takes this investigation a level deeper, examining how two different gene variants show their power — or not — depending on whether a child is abused, nurtured, or both. As Glatt describes, this study, despite its grim subject, suggests promising things about the power of nurture to magnify nature’s gifts or lift its burdens.

In the study, two candidate genes identified as potentially predisposing people to depression were checked in two different environments – a nurturing one and an abusive one. Charles concludes:

As with any behavioral genetic study, one must be careful not to overinterpret these findings, because virtually no study in behavioral genetics is consistently or completely replicated. Nonetheless, some additional points about this paper can help inform us on the nature-nurture debate. First, depression scores and categorical diagnoses of depression were significantly higher in children with a history of maltreatment versus controls even before any genetic analysis was factored in. In a similar vein, the highest average depression score of any genotype category in the unabused control children was lower than the average depression score for any genotype category in the maltreated children; genes alone weren’t likely to make the child depressed, but maltreatment alone could.
These findings suggest that, at least regarding these specific polymorphisms, nurture beats nature. This conclusion will come as a relief to believers in human free will. It also argues strongly for the identification of children at risk for maltreatment and strong actions to reverse the negative effects of this experience.

Read the whole thing for details.

Rethinking FOXP2

Earlier studies have indicated that a gene called FOXP2, possibly involved in brain development, is extremely conserved in vertebrates, except for two notable mutations in humans. This finding suggested that this gene may in some way be involved in the evolution of language, and was thus dubbed by the popular press “the language gene”. See, for instance, this and this for some recent research on the geographic variation of this gene (and related genes) and its relation to types of languages humans use (e.g., tonal vs. non-tonal). Furthermore, a mutation in this gene in humans results in inability to form grammatically correct sentences.
This week, a new study shows that this gene is highly diverse in one group of mammals – the bats:

A new study, undertaken by a joint of team of British and Chinese scientists, has found that this gene shows unparalleled variation in echolocating bats. The results, appearing in a study published in the online, open-access journal PLoS ONE on September 19, report that FOXP2 sequence differences among bat lineages correspond well to contrasting forms of echolocation.

As Anne-Marie notes, this puts a monkey-wrench in the idea that FOXP2 is exclusively involved in language, but may be involved in vocalizations in general:

Said gene might have a new function (sensorimotor) besides the one originally attributed to it (verbal language).

Jonah Lehrer notes that the same mutation that in humans eliminates ability to use or comprehend correct grammar is also found in songbirds and the gene is expressed at high levels during the periods of intense song-learning. The story is obviously getting very interesting – does this gene have something to do with vocalizations? Or with communication? Or something totally third?
Looking forward to further responses by other blogs, hopefully Afarensis, John Hawks and Language Log?
The article on FOXP2 in bats was published yesterday on PLoS ONE so you can access it for free, read, download, use, reuse, rate, annotate and comment on.
Update: Mark Liberman explains more (and takes me to task for a mistake I made in haste last night) in this post on Language Log.
Update 2: John Hawks explains.

J. Craig Venter, thoroughly exposed…

…that is, if you still think that a genome sequence tells all secrets about someone’s success in science etc. ;-)
But the new paper actually uses Venter’s personal genome to do some nifty stuff, as this is the first time a genome containing the sequences from BOTH sets of chromosomes of a single individual has been sequenced, with some interesting insights:
The Diploid Genome Sequence of an Individual Human:

We have generated an independently assembled diploid human genomic DNA sequence from both chromosomes of a single individual (J. Craig Venter). Our approach, based on whole-genome shotgun sequencing and using enhanced genome assembly strategies and software, generated an assembled genome over half of which is represented in large diploid segments (>200 kilobases), enabling study of the diploid genome. Comparison with previous reference human genome sequences, which were composites comprising multiple humans, revealed that the majority of genomic alterations are the well-studied class of variants based on single nucleotides (SNPs). However, the results also reveal that lesser-studied genomic variants, insertions and deletions, while comprising a minority (22%) of genomic variation events, actually account for almost 74% of variant nucleotides. Inclusion of insertion and deletion genetic variation into our estimates of interchromosomal difference reveals that only 99.5% similarity exists between the two chromosomal copies of an individual and that genetic variation between two individuals is as much as five times higher than previously estimated. The existence of a well-characterized diploid human genome sequence provides a starting point for future individual genome comparisons and enables the emerging era of individualized genomic information.

Also check out the synopsis and the article in The New York Times.
Oh, and while there, check out all the new articles that got published on PloS Biology today.

Can a virus make you fat?

If you are a bird, yes. If you are a human, perhaps. Stay tuned.

New on PLoS – Genetics and Computational Biology

Lots of new papers just got published in PLoS-Genetics and PLoS-Computational Biology. Here are a couple of papers that caught my eye:
From Morphology to Neural Information: The Electric Sense of the Skate:

The electric sense appears in a variety of animals, from the shark to the platypus, and it facilitates short-range prey detection where environments limit sight. Typically, hundreds or thousands of sensors work in concert. In skates, rays, and sharks, each electrosensor includes a small, innervated bulb, with a thin, gel-filled canal leading to a surface pore. While experiments have mapped single electrosensor activity, the mechanisms that integrate neural input from multiple electrosensors are still largely unknown. Here, we model the response of a precisely mapped subset of electrosensors responding in concert for a skate moving near stationary prey. Just as two ears help locate sound via time and intensity differences, we ask how a bilateral electrosensor array can contribute to electrical scene analysis. Our results show that the sensor array provides rich data for precise prey location, tuned by the morphology to render certain events, like the point of closest approach, “loud and clear.” This proof of principle makes a significant step in understanding the electric sense processing, and we recommend future experiments to compare and assess functions for the diversity of arrays found in other sharks and rays.

Digital Signal Processing Reveals Circadian Baseline Oscillation in Majority of Mammalian Genes which I have already reviewed.
The Effect of Stochasticity on the Lac Operon: An Evolutionary Perspective:

Gene expression is a process that is inherently stochastic because of the low number of molecules that are involved. In recent years it has become possible to measure the amount of stochasticity in gene expression, which has inspired a debate about the importance of stochasticity in gene expression. Little attention, however, has been paid to stochasticity in gene expression from an evolutionary perspective. We studied the evolutionary consequences of stochastic gene expression in one of the best-known systems of genetic regulation, the lac operon of E. coli, which regulates lactose uptake and metabolism. We used a computational approach, in which we let cells evolve their lac operon promoter function in a fluctuating, spatially explicit, environment. Cells can in this way adapt to the environment, but also change the amount of stochasticity in gene expression. We find that cells evolve their repressed transcription rates to higher values in a stochastic model than in a deterministic model. Higher repressed transcription rates means less stochasticity, and, hence, these cells appear to avoid stochastic gene expression in this particular system. We find that this can be explained by the fact that stochastic gene expression causes a larger delay in lactose uptake, compared with deterministic gene expression.

Mutations in gfpt1 and skiv2l2 Cause Distinct Stage-Specific Defects in Larval Melanocyte Regeneration in Zebrafish:

Programs of ontogenetic development and regeneration share many components. Differences in genetic requirements between regeneration and development may identify mechanisms specific to the stem cells that maintain cell populations in postembryonic stages, or identify other regeneration-specific functions. Here, we utilize a forward genetic approach that takes advantage of single cell type ablation and regeneration to isolate mechanisms specific to regeneration of the zebrafish melanocyte. Upon chemical ablation of melanocytes, zebrafish larvae reconstitute their larval pigment pattern from undifferentiated precursors or stem cells. We isolated two zebrafish mutants that develop embryonic melanocytes normally but fail to regenerate their melanocytes upon ablation. This phenotype suggests the regeneration-specific roles of the mutated genes. We further identified the mutations in gfpt1 and skiv2l2 and show their stage-specific roles in melanocyte regeneration. Interestingly, these mutants identify regeneration-specific functions not only in early stages of the regeneration process (skiv2l2), but also in late stages of differentiation of the regenerating melanocyte (gfpt1). We suggest that mechanisms of regeneration identified in this mutant screen may reveal fundamental differences between the mechanisms that establish differentiated cells during embryogenesis and those involved in larval or adult growth.

A Geneticist in Chernobyl

Remember when we discussed the mammal vs. bird survival at Chernobyl the other day? Well, I learned today that someone is about to go and study the humans there as well. I am not exactly sure what kind of reserch it will be, but it will have something to do with the mutations in genomes of the surrounding population.
Sarah Wallace, a senior at Duke University, will be part of the team. And you will be able to follow her adventures and her science on her blog: Notes from Ukraine (MT will not render Cyrillics well so I translated the name of the country)

Everything Important Cycles

Blogging on Peer-Reviewed Research

Microarrays have been used in the study of circadian expression of mammalian genes since 2002 and the consensus was built from those studies that approximately 15% of all the genes expressed in a cell are expressed in a circadian manner. I always felt it was more, much more.
I am no molecular biologist, but I have run a few gels in my life. The biggest problem was to find a control gene – one that does not cycle – to make the comparisons to. Actin, which is often used in such studies as control, cycled in our samples. In the end, we settled on one of the subunits of the ribosome as we could not detect a rhythm in its expression. The operative word is “could not detect”. My sampling rate was every 3 hours over a 24-hour period, so it is possible that we could have missed circadian expression of a gene that has multiple peaks, or a single very narrow peak, or a very low amplitude of cycling (it still worked as a control in our case, for different reasons). Thus, my feeling is that everything or almost everything that is expressed in a cell will be expressed in a rhythmic pattern.
If you have heard me talk about clocks (e.g., in the classroom), or have read some of my Clock Tutorials, you know that I tend to say something like “All the genes that code for proteins that are important for the core function of a cell type are expressed in a circadian fashion”. So, genes important for liver function will cycle in the liver cells, genes important for muscle function will cycle in muscle cells, etc.
But I omit to note that all such genes that are important for the function of the cell type are all the genes that are expressed in that cell. The genes not used by that cell are not expressed. But I could not go straight out and say “all the genes that are expressed in a cell are expressed in a circadian pattern”, because I had no data to support such a notion. Until yesterday.
What happened yesterday?

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Obligatory Reading of the Day

Evolution of direct development in echinoderms
It’s been several years since I last heard Rudolf Raff talk about his work and apparently he’s been busy in the meantime. The new stuff is exciting, and PZ knows how to explain it really well.


Larry just won the Triple Crown (or a trifecta, betting on the Triple Crown) with the third post in a trio of posts on a very important topic:
Facts and Myths Concerning the Historical Estimates of the Number of Genes in the Human Genome
The Deflated Ego Problem
SCIENCE Questions: Why Do Humans Have So Few Genes?
Alex Palazzo, madhadron, Ricardo Azevedo and PZ Myers add thoughtful commentary as well.
Of course, this is something that has been debated and studied (yes, in the laboratory) for a long time by people like Dan McShea so the issue is not going to be solved any time soon with a few blog posts.
But the anthropocentric bias is a big problem in studying and teaching biology and I try to at least briefly discuss the left wall of complexity (as much as it is itself contentious in the literature, I know) and the error of thinking of evolution as progressive (and inevitably leading to humans) when I teach about the origin and evolution of the current biological diversity. I wish it was easier to get that point through.

Sleep Genes are not the same as ‘Genes for sleep’

Back in the late 1990s, when people first started using various differential screens, etc. looking for elusive “genes for sleep”, I wrote in my written prelims (and reprinted it on my blog several years later):

Now the sleep researchers are jumping on the bandwagon of molecular techniques. They are screening for differences in gene expression between sleeping and awake humans (or rats or mice), searching quite openly for the “genes for sleep”. Every time they “fish out” a gene, it turns out to be Protein kinase A, a dopamine receptor, or something similar with a general function in the brain. Don’t they understand that sleep (like hibernation) is an emergent property of a multicellular brain? Unlike in the clock field, a single neuron does not carry the function – it does not sleep. Only whole (or halves of) brains can be asleep or awake. The sleep “mechanism” is not a molecular mechanism but a result of a particular pattern of neural connectivity and activity.

And, lo an behold, all the genes that affect sleep (the duration or quality of it, not timing which is guided by the circadian clock), turned out to be those “maintanance” molecules, involved in general, day-to-day activity of neurons. Most geneticists have since moved away from such a simplistic, bean-bag genetics notion of sleep and started studying sleep from a much more integrative perspective. But some persist. The newest discovery of a “sleep-gene” is just like what I predicted, a general-maintanance molecule – an ion channel:
Second Sleep Gene Identified:

A gene that controls the flow of potassium into cells is required to maintain normal sleep in fruit flies, according to researchers at the University of Wisconsin School of Medicine and Public Health (SMPH). Hyperkinetic (Hk) is the second gene identified by the SMPH group to have a profound effect on sleep in flies.
The finding supports growing evidence that potassium channels–found in humans and fruit flies alike–play a critical role in generating sleep.
“Without potassium channels, you don’t get slow waves, the oscillations shown by groups of neurons across the brain that are the hallmark of deep sleep,” says Chiara Cirelli, SMPH psychiatry professor and senior author on the latest study, which appeared in the May 16, 2007, Journal of Neuroscience.

Very cool and important for the advancement of our understanding of sleep, but surely not a “gene for sleep”.

Flirting under Moonlight on a Hot Summer Night, or, The Secret Night-Life of Fruitflies

Blogging on Peer-Reviewed Research

As we mentioned just the other day, studying animal behavior is tough as “animals do whatever they darned please“. Thus, making sure that everything is controlled for in an experimental setup is of paramount importance. Furthermore, for the studies to be replicable in other labs, it is always a good idea for experimental setups to be standardized. Even that is often not enough. I do not have access to Science but you may all recall a paper from several years ago in which two labs tried to simultaneously perform exactly the same experiment in mice, using all the standard equipment, exactly the same protocols, the same strain bought from the same supplier on the same date, the same mouse-feed, perhaps even the same colors of technicians’ uniforms and yet, they got some very different data!
The circadian behavior is, fortunately, not chaotic, but quite predictable, robust and easily replicable between labs in a number of standard model organisms. Part of the success of the Drosophila research program in chronobiology comes from the fact that for decades all the labs used exactly the same experimental apparatus, this one, produced by Trikinetics (Waltham, Massachusetts) and Carolina Biologicals (Burlington, North Carolina):
This is a series of glass tubes, each containing a single insect. An infrared beam crosses the middle of each tube and each time the fly breaks the beam, by walking or flying up and down the tube, the computer registers one “pen deflection”. All of those are subsequently put together into a form of an actograph, which is the standard format for the visual presentation of chronobiological data, which can be further statistically analyzed.
The early fruitfly work was done mainly in Drosophila pseudoobscura. Most of the subsequent work on fruitfly genetics used D.melanogaster instead. Recently, some researchers started using the same setup to do comparative studies of other Drosophila species. Many fruitfly clock labs have hundreds, even thousands, of such setups, each contained inside a “black box” which is essentially an environmental chamber in which the temperature and pressure are kept constant, noise is kept low and constant (“white noise”), and the lights are carefully controlled – exact timing of lights-on and lights-off as well as the light intensity and spectrum.
In such a setup, with a square-wave profile of light (abrupt on and off switches), every decent D.melanogaster in the world shows this kind of activity profile:
The activity is bimodal: there is a morning peak (thought to be associated with foraging in the wild) and an evening peak (thought to be associated with courtship and mating in the wild).
The importance of standardization is difficult to overemphasize – without it we would not be able to detect many of the subtler mutants, and all the data would be considered less trustworthy. Yet, there is something about standardization that is a negative – it is highly artificial. By controlling absolutely everything and making the setup as simple as possible, it becomes very un-representative of the natural environment of the animal. Thus, the measured behavior is also likely to be quite un-natural.
Unlike in the lab, the fruitflies out in nature do not live alone – they congregate with other members of the species. Unlike in a ‘black box’, the temperature fluctuates during the day and night in the real world. Also unlike the lab, the intensity and spectrum of light change gradually during the duration of the day while the nights are not pitch-black: there are stars and the Moon providing some low-level illumination as well. Thus, after decades of standardized work, it is ripe time to start investigating how the recorded behaviors match up with the reality of natural behavior in fruitflies.
Three recent papers address these questions by modifying the experimental conditions in one way or another, introducing additional environmental cues that are usually missing in the standard apparatus (and if you want to know what they found, follow me under the fold):

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Direct Spanish ancestry of the Shackleford wild horses

Shackleford ponies are often in the media around here. Some love them, some hate them, some want to preserve them, some to exterminate them, and it is not easy to get all the surplus horses adopted each year. Perhaps the new findings of their Spanish origin (DNA will tell the tale of wild horses) will tilt the scales towards their preservation, especially on the island of Corolla.
Thanks to Bill for the heads-up.