BIO101 – From Genes To Traits: How Genotype Affects Phenotype

This post was originally written in 2006 and re-posted a few times, including in 2010. Please help me locate the sources of the images – I assume they are from the text book I used at the time, but am not completely sure.

As you may know, I have been teaching BIO101 (and also the BIO102 Lab) to non-traditional students in an adult education program for about twelve years now. Every now and then I muse about it publicly on the blog (see this, this, this, this, this, this and this for a few short posts about various aspects of it – from the use of videos, to the use of a classroom blog, to the importance of Open Access so students can read primary literature). The quality of students in this program has steadily risen over the years, but I am still highly constrained with time: I have eight 4-hour meetings with the students over eight weeks. In this period I have to teach them all of biology they need for their non-science majors, plus leave enough time for each student to give a presentation (on the science of their favourite plant and animal) and for two exams. Thus I have to strip the lectures to the bare bones, and hope that those bare bones are what non-science majors really need to know: concepts rather than factoids, relationship with the rest of their lives rather than relationship with the other sciences. Thus I follow my lectures with videos and classroom discussions, and their homework consists of finding cool biology videos or articles and posting the links on the classroom blog for all to see. A couple of times I used malaria as a thread that connected all the topics – from cell biology to ecology to physiology to evolution. I think that worked well but it is hard to do. They also write a final paper on some aspect of physiology.

Another new development is that the administration has realized that most of the faculty have been with the school for many years. We are experienced, and apparently we know what we are doing. Thus they recently gave us much more freedom to design our own syllabus instead of following a pre-defined one, as long as the ultimate goals of the class remain the same. I am not exactly sure when am I teaching the BIO101 lectures again (late Fall, Spring?) but I want to start rethinking my class early. I am also worried that, since I am not actively doing research in the lab and thus not following the literature as closely, that some of the things I teach are now out-dated. Not that anyone can possibly keep up with all the advances in all the areas of Biology which is so huge, but at least big updates that affect teaching of introductory courses are stuff I need to know.

I need to catch up and upgrade my lecture notes. And what better way than crowdsource! So, over the new few weeks, I will re-post my old lecture notes (note that they are just intros – discussions and videos etc. follow them in the classroom) and will ask you to fact-check me. If I got something wrong or something is out of date, let me know (but don’t push just your own preferred hypothesis if a question is not yet settled – give me the entire controversy explanation instead). If something is glaringly missing, let me know. If something can be said in a nicer language – edit my sentences. If you are aware of cool images, articles, blog-posts, videos, podcasts, visualizations, animations, games, etc. that can be used to explain these basic concepts, let me know. And at the end, once we do this with all the lectures, let’s discuss the overall syllabus – is there a better way to organize all this material for such a fast-paced class.

Today, I tackle the important but difficult task of explaining why “gene for” idea is wrong and how to think in a more sophisticated manner about the way genes affect phenotype.


How Genotype Affects Phenotype

One often hears news reports about discoveries of a “gene for X”, e.g., gene for alcoholism, gene for homosexuality, gene for breast cancer, etc. This is an incorrect way of thinking about genes, as it implies a one-to-one mapping between genes and traits.

This misunderstanding stems from historical precedents. The very first genes were discovered decades ago with quite primitive technology. Thus, the only genes that could be discovered were those with large, dramatic effects on the traits. For instance, a small mutation (change in the sequence of nucleotides) in the gene that codes for RNA that codes for one of the four elements of the hemoglobin protein results in sickle-cell anemia. The red blood cells are, as a result, misshapen and the ability of red blood cells to carry sufficient oxygen to the cells is diminished.

Due to such dramatic effects of small mutations, it was believed at the time that each gene codes for a particular trait. Today, it is possible to measure minuscule effects of multiple genes and it is well understood that the “one gene/one trait” paradigm is largely incorrect. Most traits are affected by many genes, and most genes are involved in the development of multiple traits.

A genome is all the genetic information of an individual. Each cell in the body contains the complete genome. Genomes (i.e., DNA sequences) differ slightly between individuals of the same species, and a little bit more between genomes of closely related species, yet even more between distantly related species.

Exact DNA sequence of an individual is its genotype. The collection of all observable and measurable traits of that individual is phenotype.

If every position and every function of every cell in our bodies was genetically determined, we would need trillions of genes to specify all that information. Yet, we have only about 26,000 genes. All of our genes are very similar to the equivalent genes of chimpanzees, yet we are obviously very different in anatomy, physiology and behavior from chimpanzees. Furthermore, we share many of the same genes with fish, insects and even plants, yet the differences in phenotypes are enormous.

Thus, it follows logically that the metaphor of the genome as a blueprint for building a body is wrong. It is not which genes you have, but how those genes interact with each other during development that makes you different from another individual of the same species, or from a salmon or a cabbage.

But, how do genes interact with each other? Genes code for proteins. Some proteins interact with other proteins. Some proteins regulate the transcription or replication of DNA. Other proteins are enzymes that modify other chemicals. Yet other proteins are structural, i.e., become parts of membranes and other structures.

A slight difference in the DNA sequence will have an effect on the sequence of RNA and the sequence of the resulting protein, affecting the primary, secondary and tertiary structure of that protein. The changes in 3D shape of the protein will affect its efficiency in performing its function.

For instance, if two proteins interact with each other, and in order to do so need to bind each other, and they bind because their shapes fit into each other like lock and key, then change of shape of one protein is going to alter the efficiency of binding of the two. Changes in shapes of both proteins can either slow down or speed up the reaction. Change of rate of that one reaction in the cell will have effects on some other reaction in the cell, including the way the cell reacts to the signals from the outside.

Thus genes, proteins, other chemicals inside the cell, inter-cellular interactions and the external environment ALL affect the trait. Most importantly, as the traits are built during development, it is the interactions between all these players at all levels of organizations during development that determine the final phenotype of the organism.

The importance of the environment can be seen from the phenomenon of the norm of reaction. The same genotype, when raised in different environments results in different phenotypes. Furthermore, different genotypes respond to the same environmental changes differently from each other. One genotype may produce a taller plant at higher elevation while a slightly different genotype may respond quite the opposite: producing a shorter plant at higher elevations.

So, if genes do not code for traits, and the genome is not a blueprint, what is the best way to think about the genome and the genotype/phenotype mapping? I have given you handouts (see below) with four different alternative metaphors, at least one of which, I hope, will feel clear and memorable to each student. I will now give you a fifth such metaphor, one of my own:

Imagine that a cell is an airplane factory. It buys raw materials and sells finished airplanes. How does it do so? The proteins are the factory workers. Some of them import the materials, others are involved in the sale of airplanes. Some guard the factory from thieves, while others cook and serve food in the factory cafeteria.

But the most important proteins of this cell are those that assemble the parts of airplanes. When they need a part, e.g., a propeller, they go to the storeroom (nucleus) and check the Catalogue Of Parts (the DNA), and press the button to place an order for a particular part. Other proteins (storeroom managers) go inside and find the correct part and send it to the assembly floor (endoplasmic reticulum).

But, protein workers are themselves robots assembled out of parts right there in the same factory, and the instructions for their assembly are also in the Catalogue of Parts (DNA) in the nucleus.

Further reading:

How do you wear your genes? (PDF) by Richard Dawkins.
An analogy for the genome by Richard Harter.
It’s not just the genes, it’s the links between them by Paul Myers
PZ Myers’ Own Original, Cosmic, and Eccentric Analogy for How the Genome Works -OR- High Geekology by Paul Myers
It’s more than genes, it’s networks and systems by Paul Myers.

Previously in this series:

Biology and the Scientific Method
BIO101 – Cell Structure
BIO101 – Protein Synthesis: Transcription and Translation
BIO101: Cell-Cell Interactions
BIO101 – From One Cell To Two: Cell Division and DNA Replication
BIO101 – From Two Cells To Many: Cell Differentiation and Embryonic Development


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