Genomewide Spatial Correspondence Between Nonsynonymous Divergence and Neutral Polymorphism Reveals Extensive Adaptation in Drosophila

Surveying genome-wide coding variation within and among species gives unprecedented power to study the genetics of adaptation, in particular the proportion of amino acid substitutions fixed by positive selection. Additionally, contrasting the autosomes and the X chromosome holds information on the dominance of beneficial (adaptive) and deleterious mutations. Here we capture and sequence the complete exomes of 12 chimpanzees and present the largest set of protein-coding polymorphism to date. We report extensive adaptive evolution specifically targeting the X chromosome of chimpanzees with as much as 30% of all amino acid replacements being adaptive. Adaptive evolution is barely detectable on the autosomes except for a few striking cases of recent selective sweeps associated with immunity gene clusters. We also find much stronger purifying selection than observed in humans, and in contrast to humans, we find that purifying selection is stronger on the X chromosome than on the autosomes in chimpanzees. We therefore conclude that most adaptive mutations are recessive. We also document dramatically reduced synonymous diversity in the chimpanzee X chromosome relative to autosomes and stronger purifying selection than for the human X chromosome. If similar processes were operating in the human-chimpanzee ancestor as in central chimpanzees today, our results therefore provide an explanation for the much-discussed reduction in the human-chimpanzee divergence at the X chromosome.Pan troglodytes troglodytes | SNP | site frequency spectrum | distribution of fitness effects | faster X Q uantifying the relative importance of purifying, neutral, and positive selection in shaping divergence between species remains a challenge in evolutionary biology. Beneficial mutations are central for understanding evolution by natural selection. However, the rarity of beneficial mutations has frustrated attempts to characterize their most basic genetic properties in higher organisms (1). One way forward is to combine genome-wide surveys of polymorphism within species and between species divergence to estimate the fraction, α, of mutations that have been fixed by positive selection. Empirical studies, particularly in the Drosophila genus show that mutations fixed by positive selection can make up a sizable fraction (>50%) of the divergence between species in gene coding regions (2) but whether these results are general for mammals, for example, remains unclear. Furthermore we still know very little about the distribution of fitness effects (DFE) of these mutations and even less about their dominance in diploid organisms. Theory predicts and recent empirical studies emphasize that the demographic history as well as variation in mutation and recombination rates can blur footprints of molecular adaptation by Darwinian selection (3, 4). This in turn can complicate the inference of DFE and α (5, 6).In that context, contrasting the DFE and rates of adaptation in autosomes versus sex chromosomes is an elegant strategy to infer the genetic properties...

Section: Resultssupporting

confidence: 69%

Extensive X-linked adaptive evolution in central chimpanzees

Hvilsom

Qian

Bataillon

et al. 2012

“…Typical populations adapt to changing selection pressures by a surplus of beneficial over deleterious substitutions. Recent population-genetic studies of Drosophila genomes have shown evidence for adaptive evolution at a genome-wide level (37,13,38). Positive fitness flux (with values NΦ of order 10 per genomic substitution) (13) has been inferred from joint estimates of rate and average selection coefficient of point mutations, supporting the conclusion that a substantial fraction of the observed substitutions is adaptive at substantial levels of selection.…”

Section: Applications Of the Theoremmentioning

confidence: 83%

Fitness flux and ubiquity of adaptive evolution

Mustonen

Lässig

2010

169

247

Natural selection favors fitter variants in a population, but actual evolutionary processes may decrease fitness by mutations and genetic drift. How is the stochastic evolution of molecular biological systems shaped by natural selection? Here, we derive a theorem on the fitness flux in a population, defined as the selective effect of its genotype frequency changes. The fitnessflux theorem generalizes Fisher's fundamental theorem of natural selection to evolutionary processes including mutations, genetic drift, and time-dependent selection. It shows that a generic state of populations is adaptive evolution: there is a positive fitness flux resulting from a surplus of beneficial over deleterious changes. In particular, stationary nonequilibrium evolution processes are predicted to be adaptive. Under specific nonstationary conditions, notably during a decrease in population size, the average fitness flux can become negative. We show that these predictions are in accordance with experiments in bacteria and bacteriophages and with genomic data in Drosophila. Our analysis establishes fitness flux as a universal measure of adaptation in molecular evolution. A daptive processes have taken center stage in molecular evolutionary biology. Deep sequencing of populations opens unprecedented opportunities to trace the genomic basis of adaptation in population-genetic studies within and across species as well as in time series of evolution experiments. Various methods are used to infer natural selection from such data; however, their results lack a common gauge and are sometimes difficult to compare. This paper develops the concept of fitness flux in a population as a generic measure of adaptation applicable to molecular data. Whereas fitness characterizes the state of a population at a given point in time, fitness flux can be accumulated in a population's history over a period (a precise definition of this quantity will be given below). Fitness flux, not fitness, turns out to be the right variable to show that adaptive evolution is a generic state of natural populations. The notion of fitness flux is already implicitly contained in Fisher's fundamental theorem of natural selection (1), which states that any fitness difference within a population leads to adaptation in an evolution process governed by natural selection alone. The fitness flux of this deterministic process equals the (additive) fitness variance in the population. Hence, the flux is positive when adaptation occurs and zero otherwise.Generalizing this picture to realistic processes of molecular evolution has been a long-standing problem (2-8). The solution presented here involves a number of important conceptual steps. First, molecular processes are always stochastic because of genetic drift and mutations, and we include these forces into a stochastic theory of fitness flux. Second, we extend the observation of this dynamics to the time scales of genomic data, describing populations by histories of genotype composition and demography that may extend beyond their ...

“…Indeed, understanding this underlying distribution of selection coefficients has been a central focus of evolutionary biology over the past five decades (24). Contrary to recent inference made in Drosophila favoring models of frequent recurrent and strongly positive selection (25), but similar to inferences from genome-wide analyses of polymorphisms from S. cerevisiae and S. paradoxus (26), our direct observations in yeast are remarkably consistent with a nearly neutral model of molecular evolution (27), in which a large proportion of new mutations are strongly deleterious and are eliminated via purifying selection, whereas the great majority of remaining mutations are nearly neutral, with dynamics largely dictated by genetic drift (Fig. 4).…”

Section: Discussionmentioning

confidence: 99%

Experimental illumination of a fitness landscape

Hietpas¹,

Jensen

Bolon³

2011

311

369

The genes of all organisms have been shaped by selective pressures. The relationship between gene sequence and fitness has tremendous implications for understanding both evolutionary processes and functional constraints on the encoded proteins. Here, we have exploited deep sequencing technology to experimentally determine the fitness of all possible individual point mutants under controlled conditions for a nine-amino acid region of Hsp90. Over the past five decades, limited glimpses into the relationship between gene sequence and function have sparked a long debate regarding the distribution, relative proportion, and evolutionary significance of deleterious, neutral, and advantageous mutations. Our systematic experimental measurement of fitness effects of Hsp90 mutants in yeast, evaluated in the light of existing population genetic theory, are remarkably consistent with a nearly neutral model of molecular evolution.