Just because I was busy with the conference does not meen that PLoS stopped the virtual presses to accommodate me! Of course, there are a bunch of cool new papers in PLoS Genetics, PLoS Computational Biology, PLoS Pathogens and PLoS ONE that have been published last week. As always, you should rate the articles, post notes and comments and send trackbacks when you blog about the papers. Here are my own picks for the week – you go and look for your own favourites:
Action Potential Initiation in the Hodgkin-Huxley Model:
In 1952, Hodgkin and Huxley described the underlying mechanism for the firing of action potentials through which information is propagated in the nervous system. Hodgkin and Huxley’s model relies on the opening and closing of channels, selectively allowing ions to move across the membrane. In the original picture, the channels open independently of one another. A recent paper argues that this model is incapable of modeling a set of action potential data recorded in the cortical neurons of cats. Instead the authors suggest that to model their data it is necessary to conclude that ion channels open cooperatively, so that opening one channel increases the chance that another channel opens. We analyze the initiation of action potentials using a method from theoretical physics, the path integral. We demonstrate that deviations of the data from the predictions of the Hodgkin-Huxley model hinge on measurement of the noise strength.
Contrasting Mode of Evolution at a Coat Color Locus in Wild and Domestic Pigs:
This study addresses why coat colors of domestic animals are so variable, while those of their wild ancestors are so uniform. Specifically, we asked whether this was the result of (i) relaxed purifying selection, (ii) that some mutations affect both coat color and another trait under strong selection (for instance behavior), or (iii) direct human selection for altered coat color phenotypes. We investigated genetic variation in the melanocortin receptor 1 (MC1R) gene among wild and domestic pigs from both Europe and Asia. Though we found a similar number of mutations in wild and domestic pigs, the nature of the mutations was strikingly different. All mutations found among wild boars were silent, i.e., they did not change the protein sequence. This implies strong purifying selection in the wild that maintains camouflage coat color. In contrast, nine out of ten mutations found in domestic pigs altered the protein sequence, thereby drastically transforming the resulting coat color. These results demonstrate that early farmers intentionally selected pigs with novel coat coloring. Their motivations could have been as simple as a preference for the exotic or selection for reduced camouflage to facilitate animal husbandry and/or to make the domesticated forms distinct from their wild ancestor.
Sequences From First Settlers Reveal Rapid Evolution in Icelandic mtDNA Pool:
Ancient DNA studies have great potential to shed light on the evolution of populations because they provide the opportunity to sample from the same population at different points in time. However, ancient DNA studies are often based on DNA extracted from only one or a few individuals and, therefore, do not lend themselves to statistical inference. Here, we describe the analysis of a sample of mitochondrial DNA (mtDNA) control region sequences from 68 Icelandic skeletal remains that are about 1,000 years old, from the time that Iceland was first settled. We show that the ancient Icelandic mtDNA sequences are more closely related to sequences from contemporary inhabitants of Scotland, Ireland, and Scandinavia (and several other European populations) than to those from the modern Icelandic population. It appears that the array of sequences carried by the first generations of Icelanders was better preserved in the gene pools of their ancestors than among their modern descendants because of a faster rate of evolution due to genetic drift in the Icelandic mtDNA pool during the last 1,100 years. These results demonstrate the inferential power that can be gained from studies by applying the methods of population genetics to samples of ancient DNA sequences.
Converging on the Origins of Axonal Ion Channel Clustering:
The high-density clustering of voltage-gated Na+ channels and KCNQ2/3 K+ channels at the axon initial segment (AIS; see Figure 1A) and nodes of Ranvier (Figure 1B) is essential for the final integration of synaptic inputs and the initiation and rapid propagation of action potentials (APs) in neurons [1]-[3]. The AIS also marks the transition between the axonal and somatodendritic domains of the neuron, and its molecular integrity is required to maintain neuronal polarity [4],[5]. Thus, the AIS acts as both a key functional and structural bridge between neuronal input and output. Previously, the cytoskeletal and scaffolding protein ankyrinG was shown to be essential for the clustering of Na+ channels at the AIS and at the peripheral nervous system nodes of Ranvier [6]-[8]. Efforts to identify the molecular basis of Na+ channel clustering at the AIS showed that all mammalian Na+ channels have a cytoplasmic anchor motif that mediates their interaction (and AIS clustering) with ankyrinG [9],[10]. Subsequently, a comparison between Na+ channels and KCNQ2/3 K+ channels revealed the surprising fact that these two types of channels have the ankyrinG interaction and anchor motif in common [11]. While these anchor motifs are highly conserved among vertebrates, they are not found among invertebrates. This observation led to the fascinating question of how and why ion channels from two different gene families evolved a common amino acid sequence that mediates their clustering and localization at the AIS and nodes of Ranvier.
The greater wax moth Galleria mellonella has been widely used as a heterologous host for a number of fungal pathogens including Candida albicans and Cryptococcus neoformans. A positive correlation in pathogenicity of these yeasts in this insect model and animal models has been observed. However, very few studies have evaluated the possibility of applying this heterologous insect model to investigate virulence traits of the filamentous fungal pathogen Aspergillus fumigatus, the leading cause of invasive aspergillosis. Here, we have examined the impact of mutations in genes involved in melanin biosynthesis on the pathogenicity of A. fumigatus in the G. mellonella model. Melanization in A. fumigatus confers bluish-grey color to conidia and is a known virulence factor in mammal models. Surprisingly, conidial color mutants in B5233 background that have deletions in the defined six-gene cluster required for DHN-melanin biosynthesis caused enhanced insect mortality compared to the parent strain. To further examine and confirm the relationship between melanization defects and enhanced virulence in the wax moth model, we performed random insertional mutagenesis in the Af293 genetic background to isolate mutants producing altered conidia colors. Strains producing conidia of previously identified colors and of novel colors were isolated. Interestingly, these color mutants displayed a higher level of pathogenicity in the insect model compared to the wild type. Although some of the more virulent color mutants showed increased resistance to hydrogen peroxide, overall phenotypic characterizations including secondary metabolite production, metalloproteinase activity, and germination rate did not reveal a general mechanism accountable for the enhanced virulence of these color mutants observed in the insect model. Our observations indicate instead, that exacerbated immune response of the wax moth induced by increased exposure of PAMPs (pathogen-associated molecular patterns) may cause self-damage that results in increased mortality of larvae infected with the color mutants. The current study underscores the limitations of using this insect model for inferring the pathogenic potential of A. fumigatus strains in mammals, but also points to the importance of understanding the innate immunity of the insect host in providing insights into the pathogenicity level of different fungal strains in this model. Additionally, our observations that melanization defective color mutants demonstrate increased virulence in the insect wax moth, suggest the potential of using melanization defective mutants of native insect fungal pathogens in the biological control of insect populations.
Computational models of motor control have often explained the straightness of horizontal planar reaching movements as a consequence of optimal control. Departure from rectilinearity is thus regarded as sub-optimal. Here we examine if subjects may instead select to make curved trajectories following adaptation to force fields and visuomotor rotations. Separate subjects adapted to force fields with or without visual feedback of their hand trajectory and were retested after 24 hours. Following adaptation, comparable accuracies were achieved in two ways: with visual feedback, adapted trajectories in force fields were straight whereas without it, they remained curved. The results suggest that trajectory shape is not always straight, but is also influenced by the calibration of available feedback signals for the state estimation required by the task. In a follow-up experiment, where additional subjects learned a visuomotor rotation immediately after force field, the trajectories learned in force fields (straight or curved) were transferred when directions of the perturbations were similar but not when directions were opposing. This demonstrates a strong bias by prior experience to keep using a recently acquired control policy that continues to produce successful performance inspite of differences in tasks and feedback conditions. On relearning of force fields on the second day, facilitation by intervening visuomotor rotations occurred only when required motor adjustments and calibration of feedback signals were similar in both tasks. These results suggest that both the available feedback signals and prior history of learning influence the choice and maintenance of control policy during adaptations.
Humans and Mice Express Similar Olfactory Preferences:
In humans, the pleasantness of odors is a major contributor to social relationships and food intake. Smells evoke attraction and repulsion responses, reflecting the hedonic value of the odorant. While olfactory preferences are known to be strongly modulated by experience and learning, it has been recently suggested that, in humans, the pleasantness of odors may be partly explained by the physicochemical properties of the odorant molecules themselves. If odor hedonic value is indeed predetermined by odorant structure, then it could be hypothesized that other species will show similar odor preferences to humans. Combining behavioral and psychophysical approaches, we here show that odorants rated as pleasant by humans were also those which, behaviorally, mice investigated longer and human subjects sniffed longer, thereby revealing for the first time a component of olfactory hedonic perception conserved across species. Consistent with this, we further show that odor pleasantness rating in humans and investigation time in mice were both correlated with the physicochemical properties of the molecules, suggesting that olfactory preferences are indeed partly engraved in the physicochemical structure of the odorant. That odor preferences are shared between mammal species and are guided by physicochemical features of odorant stimuli strengthens the view that odor preference is partially predetermined. These findings open up new perspectives for the study of the neural mechanisms of hedonic perception.
Complete Genome Sequence of the Aerobic CO-Oxidizing Thermophile Thermomicrobium roseum:
In order to enrich the phylogenetic diversity represented in the available sequenced bacterial genomes and as part of an “Assembling the Tree of Life” project, we determined the genome sequence of Thermomicrobium roseum DSM 5159. T. roseum DSM 5159 is a red-pigmented, rod-shaped, Gram-negative extreme thermophile isolated from a hot spring that possesses both an atypical cell wall composition and an unusual cell membrane that is composed entirely of long-chain 1,2-diols. Its genome is composed of two circular DNA elements, one of 2,006,217 bp (referred to as the chromosome) and one of 919,596 bp (referred to as the megaplasmid). Strikingly, though few standard housekeeping genes are found on the megaplasmid, it does encode a complete system for chemotaxis including both chemosensory components and an entire flagellar apparatus. This is the first known example of a complete flagellar system being encoded on a plasmid and suggests a straightforward means for lateral transfer of flagellum-based motility. Phylogenomic analyses support the recent rRNA-based analyses that led to T. roseum being removed from the phylum Thermomicrobia and assigned to the phylum Chloroflexi. Because T. roseum is a deep-branching member of this phylum, analysis of its genome provides insights into the evolution of the Chloroflexi. In addition, even though this species is not photosynthetic, analysis of the genome provides some insight into the origins of photosynthesis in the Chloroflexi. Metabolic pathway reconstructions and experimental studies revealed new aspects of the biology of this species. For example, we present evidence that T. roseum oxidizes CO aerobically, making it the first thermophile known to do so. In addition, we propose that glycosylation of its carotenoids plays a crucial role in the adaptation of the cell membrane to this bacterium’s thermophilic lifestyle. Analyses of published metagenomic sequences from two hot springs similar to the one from which this strain was isolated, show that close relatives of T. roseum DSM 5159 are present but have some key differences from the strain sequenced.
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