Adaptive genic evolution in the Drosophila genomes

Abstract

Determining the extent of adaptive evolution at the genomic level is central to our understanding of molecular evolution. A suitable observation for this purpose would consist of polymorphic data on a large and unbiased collection of genes from two closely related species, each having a large and stable population. In this study, we sequenced 419 genes from 24 lines of Drosophila melanogaster and its close relatives. Together with data from Drosophila simulans, these data reveal the following. (i) Approximately 10% of the loci in regions of normal recombination are much less polymorphic at silent sites than expected, hinting at the action of selective sweeps. (ii) The level of polymorphism is negatively correlated with the rate of nonsynonymous divergence across loci. Thus, even under strict neutrality, the ratio of amino acid to silent nucleotide changes (A:S) between Drosophila species is expected to be 25-40% higher than the A:S ratio for polymorphism when data are pooled across the genome. (iii) The observed A/S ratio between species among the 419 loci is 28.9% higher than the (adjusted) neutral expectation. We estimate that nearly 30% of the amino acid substitutions between D. melanogaster and its close relatives were adaptive. (iv) This signature of adaptive evolution is observable only in regions of normal recombination. Hence, the low level of polymorphism observed in regions of reduced recombination may not be driven primarily by positive selection. Finally, we discuss the theories and data pertaining to the interpretation of adaptive evolution in genomic studies.

Fig. 1.

Relationship between recombination rate and θ_W for silent sites (Spearman rank correlation R = 0.53, P < 10⁻¹⁵) (Upper) and Tajima's D for silent sites (R = 0.16, P = 8.6 × 10⁻⁴) (Lower).

Fig. 2.

MK tables with FI = 1 can combine to produce a table of FI > 1, thus appearing nonneutral. Both hypothetical loci appear neutral as the ratio of nonsynonymous (A) to synonymous (S) changes within each table is the same for polymorphism (P) and divergence (D). The level of polymorphism between loci, however, is not the same, with a P:D ratio of 0.3 and 1.0 for the first and second tables, respectively. Although the different levels of polymorphism may be incompatible with strict neutrality, this rejection, if true, applies only to the polymorphic portion of the data. By contrast, the MK test is usually used to infer positive selection in the divergence among species.

Fig. 3.

Correlation between P/D and A/S, where P (polymorphism), D (divergence), A (amino acid altering), and S (silent) are the margins for the 2 × 2 contingency table of the MK test. P/D denotes the size of the genealogy, and A/S denotes the selective constraint of the gene. Pearson's R = −0.188 and P = 0.0001. Seven genes have a P/D ratio >5 and are shown on the top (solid diamonds). When the contingency tables are summed up, genes with a larger P/D ratio generally contribute proportionately more to the total.

Fig. 4.

Polymorphism A/S ratios in D. melanogaster, binned by the frequency of the derived variants. The first and last three gray bars represent singletons, doubletons, and tripletons. The middle six gray bars have a frequency increment of 0.1. The nine bars with frequency >0.19 are designated high-frequency classes (see Results). Their A/S ratios, being statistically indistinguishable, may be considered the ratio for neutral polymorphic variants. The A/S ratio for high-frequency variants, as well as that for all variants, is shown by the open bar. The black bar gives the divergence A/S ratio between D. melanogaster and D. simulans.