Exercise 14.2

X Versus Autosome Evolution across the Genome

(This exercise is based on Singh, N. D., A. M. Larracuente, and A. G. Clark. 2008. Contrasting the efficacy of selection on the X and autosomes in Drosophila. Molecular Biology and Evolution 25: 454–467.)

(Note: The reference above links directly to the article on the journal’s website. In order to access the full text of the article, you may need to be on your institution’s network [or logged in remotely], so that you can use your institution’s access privileges.)

INTRODUCTION

New mutations that arise on the X chromosome can have different likelihoods of becoming fixed in the population than their autosomal counterparts. This differential likelihood arises because the effect of a recessive mutation on an autosome is only expressed in homozygotes, whereas the effect of a similar recessive mutation that arises on the X chromosome in a male is fully expressed. Thus, advantageous recessive mutations are more likely to become fixed if they are on the X chromosome than if they are on an autosome. In contrast, a slightly deleterious recessive mutation would more likely become fixed if it were on an autosome than if it were on the X chromosome. Thus, if mutation rates are independent of whether a gene is X-linked or autosomal, and if natural selection operates in a consistent manner across the genome, different patterns of evolution are expected on the X chromosome than on the autosomes.

The sequencing of the complete genomes of a dozen species of Drosophila (completed in 2007) provides a rich opportunity to examine the molecular evolution of a large number of X-linked and autosomal genes across a phylogeny. Nadia Singh and Amanda Larracuente, respectively a postdoctoral fellow and graduate student in the laboratory run by Andrew Clark at Cornell, took advantage of the data generated by the sequencing of the 12 Drosophila genomes to examine the relative rates of X-linked and autosomal genetic changes.

QUESTIONS

Figure 1 A phylogeny for five of the Drosophila species, depicting results for changes at four fold degenerate sites, which are third-codon-position sites where all four different third-position codons encode the same amino acid. Red indicates regions of the phylogeny where the rate of change of these four-fold degenerate sites is significantly higher on the X than on the autosomes, while blue indicates regions where the rate of change is significantly higher on the autosomes. Black indicates regions of the phylogeny where the rates are not significantly different between the X and the autosomes, while green is for branches that haven’t been tested.

Question 1. Which species is most closely related to D. yakuba?

Question 2. Did D. simulans last share a common ancestor with D. melanogaster before, after, or at the same time as when D. sechellia last shared a common ancestor with D. melanogaster?

Question 3. Is the rate of divergence at neutral sites on the X chromosome faster, slower, or about the same as that on the autosomes along the lineage leading to D. erecta? Along the lineage leading to D. simulans?

Figure 2 A phylogeny for all 12 Drosophila species, depicting results for amino acid changes. The same color codes are used as before.

Question 4. What pattern would you expect if amino acid changes are largely due to recessive advantageous mutations?

Question 5. What color are the regions of the phylogeny that are consistent with the pattern predicted under amino acid changes being advantageous and recessive? What conclusions can you draw about how well the data fit this recessive, advantageous model of evolution?

Table 1 The median (with mean in parentheses) divergence at four-fold degenerate sites (d_S₄) and amino acid changing sites (d_N) for five of the species at both X and the autosomes. It also shows ω: the ratio of d_N to d_S₄ for these species.

Question 6. Which two species shows the highest divergence at four-fold degenerate sites at both X-linked and autosomal genes?

Question 7. Is the average value of ω closer to one-tenth, one-fifth, or one-third?

Question 8. Based on the average value of ω, which mode of selection is predominate: balancing, positive, or negative?