Thursday, December 22, 2011
Monday, December 19, 2011
The investigation of parallel evolution is a powerful paradigm to study mechanisms of adaptation. This review and opinion paper stresses the fact that although remarkable examples have been studied, molecular bases of adaptation are still poorly understood in the vast majority of cases.
In rare examples, a genetic variation has been linked to repeated and independent adaptation. In the examples of Mc1r , multiple mutations occurred in the same gene independently leading to different coat colours in mice. In humans, lactose tolerance was acquired repeatedly due to mutations occurring independently in the same genes in different populations. In the paper, authors describe mutations in Pitx1 which have occurred repeatedly in three spine stickleback fish leading to reduced pelvic armor plate which differentiates the sea water from the fresh water specie. These observations have been validated by transgenic animals demonstrating the fact that Pitx1 is the genetic basis of this recurrent phenotype and form of adaptation.
As a reader naïve to the field, I found that this paper describes well the obstacles that researchers are facing in the investigation of the molecular basis of adaptation. Genetic data is sparse and the vast majority of species have not been sequenced. For those species who have been, only a small number of specimens were sequences. Surprisingly, despite this lack of genetic (or genomic) data, the authors have categorized the different genetic bases to parallel adaptation into 3 groups : i) same mutation in the same gene, ii) different mutation in the same gene and iii) mutations in different genes. These very “formal” distinctions have stirred many questions and intrigued many of the students attending the tutorial including myself. Maybe the fascination for species has drawn the authors to describe different “species” of mutations. Others and myself thought that, given the scarcity of genetic or genomic data, these questions may be too premature. Trained in medical genetics, I have repeatedly experienced the situation “iii)” where mutations at many different loci may give rise to the same phenotypic manifestation but I was reminded, however, that “disease” is not “adaptation” and although there may be many different ways of disrupting a mechanism only few may lead to specific advantages. We also discussed the fact that these different “groups” may also be related to the complexity of the phenotype, e.g. : lactose tolerance, related to the function of one enzyme can only be related to the category “i) or ii)” as opposed to much more composite and complexe phenotype such as “social cognition” for example which would likely fall under the category “iii)”.
This is a perspective paper and there are no methods or results to critique. Authors conclude that next generation sequencing will “come to the rescue” of the complex issue of genotype-phenotype correlations and how they relate to adaptation. I also share the optimism of the authors and believe that genomic technologies will provide a wealth of “unbiased” (as opposed to candidate gene approaches) data that will allow identifying the basis of many adaptive processes. The following papers studied in the tutorial showed that this is the case and that many paradigms of evolution are being challenged now that data is available (cf. in other blogs the genomic signatures of adaptation such as selective sweeps). What I enjoyed the most in this tutorial were the discussions between students and senior researchers using the same tools and studying the same, phenomenon (mutations, phenotypes) but driven by very different questions.
Best quote during the tutorial: “The theory looked really sexy until the data was available”.
(Posted by MRR for Sebastien Jacquemont)
Friday, December 16, 2011
by Ricardo Kanitz, based on the paper by Hernandez et al. published in Science (2011).
One of the main topics in evolution is – as it has always been – human evolution. Many new methods are applied first to humans; other methods, which are not applied there, often come to humans at some point anyway. This is particularly true in the field of genomics and it is no surprise since we are talking about our own species' evolution. The study commented here addresses an interesting general question in the subject. How selection shaped (if at all) our genomes?
As it follows, they proposed a scenario of background purifying selection to explain the observed pattern. In Figure 3B above, they showed the fit of simulations with background selection (purple, green and orange) with the observations (dark blue, light blue and red). Such a fit appears to be very good and they conclude that the pattern they observed is better explained by purifying selection (a.k.a. strict neutrality) than by recurrent positive selection.
Finally, given (1) the fact that the observations did not fit the predictions of their (rather extreme) selection model, and (2) that a neutral model was able to explain the observations, the general conclusion is that classic selective sweeps resulting from strong positive selection were quite rare in the recent human evolution.
Although it would be interesting to see how the results would look like with lower (and more realistic) values for α and s, this study brings about the interesting discussion of the modus operandi of human adaptation. Classical examples based on phenotypes show that humans underwent recurrent adaptations when it comes to diet, immune response and skin pigmentation. The molecular mechanisms underlying these, however, might not be as simple as the “Classic Selective Sweeps”. Complex genetic architectures linking small effect polygenic variants, for example, may lead to soft sweeps; which do not leave the same sort of signature and can easily be missed in the background noise created by the potentially overwhelming neutral evolution. Therefore, there are still many unknown features related to recent human evolution – especially concerning non-neutral evolution – and the growing availability of data coupled with better analytical methods may bring new and possibly surprising results in the coming years of scientific investigation.