Selection on codon bias

In a wide variety of organisms, synonymous codons are used with different frequencies, in a phenomenon known as codon bias. In an article just published in the Annual Review of Genetics, Ruth and Dmitri discuss the current understanding of the ways in which natural selection participates in the creation and maintenance of codon bias. We also raise several open questions: (i ) Is natural selection on codon bias always weak as suggested by a number of studies or is it weak only at equlibrium? (ii ) What determines the identity of the selectively optimal codons? (iii ) How do shifts in the identity of optimal codons take place? (iv) What is the exact nature of selection on codon bias?

High rate of transposable element-induced adaptation in Drosophila

PloS Biology today published a paper by Gonzalez, J., Lenkov, K., Lipatov, M., Macpherson, J.M., and D.A. Petrov on the high rate of recent transposable element-induced adaptations in Drosophila melanogaster. In this work, we describe the first comprehensive genome-wide screen for recent adaptive TE insertions in D. melanogaster. Using several independent criteria, we identified a set of 13 adaptive TEs and estimate that 25-50 TEs have played adaptive roles since the migration of D. melanogaster out of Africa. We show that most of these adaptive TEs are likely to be involved in regulatory changes and appear to be involved in adaptation to the temperate climate. We argue that most identified adaptive TEs are destined to be lost from the D. melanogaster population but that they do contribute significantly to local adaptation in this species.

High redundancy and little new functionality among duplicated genes in yeast

PLoS Genetics published today a paper by Dean, J., Davis, J.C., Davis, R.W., and D.A. Petrov on the pervasive redundancy and apparent lack of new functionality among duplicated genes in yeast. We built a large number of yeast strains carrying single and double gene deletions of duplicated genes and measured their growth rates in rich medium. Using these data, we determined that many duplicated genes are functionally redundant to a substantial degree. We also demonstrated that the fitness effects of double deletions of duplicate genes are indistinguishable from our best estimate of the fitness effects of deletions of their ancestral singleton genes. We therefore argued that many duplicate genes do not gain substantial new functionality at least in the rich medium. Our results suggest that subfunctionalization does not generally proceed to completion, even after very long periods of time, and that neofunctionalization is either rare or of little consequence, at least under some growth conditions. This work was a collaboration between the Petrov and Davis labs.

Fake partial selective sweeps

A beneficial mutation that has nearly but not yet fixed in a population produces a characteristic haplotype configuration, called a partial selective sweep. Whether nonadaptive processes might generate similar haplotype configurations has not been extensively explored. In a paper by Macpherson, J.M., Gonzalez, J., Witten, D., Davis, J.C., Rosenberg, N., Hirsh, A.E., and D. A. Petrov that was just published by Molecular Biology and Evolution, we demonstrate that a number of non-adaptive processes can indeed lead to haplotype configurations that resemble partial selective sweeps. We show that recent bottlenecks are particularly powerful in this regard. This work emphasizes the importance of knowing demographic history in interpreting population genetic data.

High rate of strong adaptation in Drosophila

In a study just published in Genetics and authored by Macpherson, J.M., Sella, G., Davis, J.C., and D. A. Petrov, we study the correspondence between divergence at protein-coding sites and neutral polymorphism using genomewide data from Drosophila simulans. We find that neutral polymorphism is both lower and less homogeneous where nonsynonymous divergence is higher and that the spatial structure of this correlation is best explained by the action of strong positive selection. We introduce a method to infer the rate and selective strength of adaptation. Our results independently confirm a high rate of adaptive substitution (~1/3000 generations) and newly suggest that many adaptations are of surprisingly great selective effect (~1%), reducing the effective population size by ~15% even in highly recombining regions of the genome.

Shigella loses genes at a very high rate

Shigella strains are ecotypes of E.coli and were only given a separate name because all Shigella strains cause a distinct disease (dysentery). Ruth Hershberg led a study (just published in Genome Biology) that demonstrated that Shigella strains lose genes at much higher rates than other E. coli strains and that this is largely due to a genome-wide reduction in the strength of purifying selection. This reduction in the strength of selection might be a result of the different lifestyle of Shigella strains compared to other E. coli strains.

Tempo and mode of genome size evolution

Eukaryotic genome size varies over five orders of magnitude. The genome size distribution is strongly skewed to small values. Genome size is highly correlated to a number of phenotypic traits, suggesting that the relative lack of large genomes in eukaryotes is due to selective removal. In a study by Oliver, M.J., Petrov, D.A., Ackerly, D., Falkowski, P.G., and O.M. Schofield that just came out in Genome Research we demonstrated that the rate of genome size evolution is proportional to genome size, with the fastest rates occurring in the largest genomes. Such a simple proportional model of genome size evolution appears to be virtually universal across eukaryotes. This model explains the skewed distribution of eukaryotic genome sizes without invoking strong selection against large genomes.

Pesticide resistance by transposition

Using a genomic screen for adaptive transpositions in Drosophila, we have identified an adaptive insertion of a transposable element into a conserved gene involved in choline metabolism. We called this gene CHKov1. The transposition truncates CHKov1 and generates a new functional protein in the process. We hypothesize and then demonstrate that the truncated allele of CHKov1 confers increased resistance to organophosphate pesticides and has spread in D. melanogaster recently and under the pressure of positive natural selection. The paper describing this research and authored by Yael Aminetzach, Mike Macpherson, and D.A. Petrov was just published by Science. Here is how Science describes this work. This paper was also evlauated on Faculty 1000: http://www.f1000biology.com/article/id/1027308/evaluation and was rated as a Must Read.