Effective Population Size and the Efficacy of Selection on the X Chromosomes of Two Closely Related Drosophila Species

Abstract

The prevalence of natural selection relative to genetic drift is of central interest in evolutionary biology. Depending on the distribution of fitness effects of new mutations, the importance of these evolutionary forces may differ in species with different effective population sizes. Here, we survey population genetic variation at 105 orthologous X-linked protein coding regions in Drosophila melanogaster and its sister species D. simulans, two closely related species with distinct demographic histories. We observe significantly higher levels of polymorphism and evidence for stronger selection on codon usage bias in D. simulans, consistent with a larger historical effective population size on average for this species. Despite these differences, we estimate that <10% of newly arising nonsynonymous mutations have deleterious fitness effects in the nearly neutral range (i.e., −10 < Nes < 0) in both species. The inferred distributions of fitness effects and demographic models translate into surprisingly high estimates of the fraction of “adaptive” protein divergence in both species (∼85–90%). Despite evidence for different demographic histories, differences in population size have apparently played little role in the dynamics of protein evolution in these two species, and estimates of the adaptive fraction (α) of protein divergence in both species remain high even if we account for recent 10-fold growth. Furthermore, although several recent studies have noted strong signatures of recurrent adaptive protein evolution at genes involved in immunity, reproduction, sexual conflict, and intragenomic conflict, our finding of high levels of adaptive protein divergence at randomly chosen proteins (with respect to function) suggests that many other factors likely contribute to the adaptive protein divergence signature in Drosophila.

A second-generation assembly of the Drosophila simulans genome provides new insights into patterns of lineage-specific divergence

“…The ''faster'' faster-X pattern in D. simulans suggests that a larger proportion of newly arising mutations are beneficial in D. simulans (as weaker purifying selection in the D. simulans lineage seems less likely). On the other hand, the ''slower'' slower-X pattern for synonymous sites in D. simulans conforms with expectations of stronger codon usage bias reported in D. simulans than D. melanogaster (Akashi 1995;Akashi and Schaeffer 1997;McVean and Vieira 2001;Nielsen et al 2007;Andolfatto et al 2011b). …”

“…In particular, the fate of slightly deleterious mutations occurring in species with large N e is predicted to be more efficiently removed by natural selection, whereas in species with smaller N e , a larger fraction of these mutations can instead be fixed by random genetic drift. Of the two species, D. simulans is believed to have had the historically larger N e based on comparisons of levels of nucleotide diversity and from patterns of codon usage bias (Aquadro et al 1988;Akashi 1995;Moriyama and Powell 1996;Andolfatto 2001;Andolfatto et al 2011b). Our finding of generally lower rates of divergence in D. simulans is broadly consistent with this view.…”

Weak Selection and Protein Evolution

“…Excess rare polymorphisms and higher r pd for nonsynonymous compared to synonymous variation appear to be general patterns in viral (Edwards et al 2006;Pybus et al 2006;Hughes 2009) and bacterial genomes (Hughes 2005;Charlesworth and Eyre-Walker 2006;Rocha et al 2006;Hughes et al 2008) as well as in animal mtDNA (Ballard and Kreitman 1994;Nachman et al 1996;Rand and Kann 1996;Hasegawa et al 1998;Wise et al 1998;Weinreich and Rand 2000;Gerber et al 2001;Subramanian et al 2009). Similar patterns have been noted in nuclear genes from yeast (Doniger et al 2008;Liti et al 2009), Drosophila (Akashi 1996;Fay et al 2002;Loewe et al 2006;Andolfatto et al 2011), humans (Cargill et al 1999;Sunyaev et al 2000;Hughes et al 2003;Williamson et al 2005;Boyko et al 2008;Keightley and Halligan 2011;Subramanian 2012), mice (Halligan et al 2010), and plants (Bustamante et al 2002;Nordborg et al 2005;Foxe et al 2008;Fujimoto et al 2008;Gossmann et al 2010;Branca et al 2011;. Excess rare polymorphism could reflect very strongly deleterious mutations if the number of sampled chromosomes is very high, but sample sizes in most of these studies do not approach such levels.…”

Extensive X-linked adaptive evolution in central chimpanzees

“…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.…”

“…Second, depending on the reproductive variance in the two sexes, we expect X chromosome regions to have between 50 and 100% of the effective size of autosomes, undergo more genetic drift, and thus be more prone to accumulate more slightly deleterious mutations. Empirical evidence for increased levels of adaptation in X-linked regions remains elusive (7), except for a unique instance of a newly formed neo-X chromosome in Drosophila miranda (9) and a recent analysis of polymorphism and divergence between Drosophila melanogaster and Drosophila simulans for about 100 genes in X-linked regions (2). In human studies, Xlinked variation is lower than autosomal variation close to genes suggesting that selection affects X chromosomes more than autosomes, but Europeans have a genome-wide relative decrease in Xlinked variation when comparing with Africans, suggesting that genetic drift has specifically affected X chromosome in Europeans (3,(10)(11)(12).…”