Molecular Evolution in the Drosophila melanogaster Species Subgroup: Frequent Parameter Fluctuations on the Timescale of Molecular Divergence

Abstract

Although mutation, genetic drift, and natural selection are well established as determinants of genome evolution, the importance (frequency and magnitude) of parameter fluctuations in molecular evolution is less understood. DNA sequence comparisons among closely related species allow specific substitutions to be assigned to lineages on a phylogenetic tree. In this study, we compare patterns of codon usage and protein evolution in 22 genes (.11,000 codons) among Drosophila melanogaster and five relatives within the D. melanogaster subgroup. We assign changes to eight lineages using a maximum-likelihood approach to infer ancestral states. Uncertainty in ancestral reconstructions is taken into account, at least to some extent, by weighting reconstructions by their posterior probabilities. Four of the eight lineages show potentially genomewide departures from equilibrium synonymous codon usage; three are decreasing and one is increasing in major codon usage. Several of these departures are consistent with lineage-specific changes in selection intensity (selection coefficients scaled to effective population size) at silent sites. Intron base composition and rates and patterns of protein evolution are also heterogeneous among these lineages. The magnitude of forces governing silent, intron, and protein evolution appears to have varied frequently, and in a lineage-specific manner, within the D. melanogaster subgroup. U NDERSTANDING the forces governing the origins and evolutionary fates of DNA mutations is central to the study of molecular evolution. A great deal of attention has been focused on determining the relative contributions of genetic drift and natural selection to patterns of divergence among genomes (reviewed in Ohta 2002). However, the magnitude, timescale, and genomic breadth of fluctuations in molecular evolutionary forces remain to be studied systematically. Such knowledge is critical for modeling the causes of molecular evolution and is necessary for designing tests of adaptive and deleterious evolution and methods for phylogenetic inference and ancestral state reconstruction.Determinants of molecular evolution include mutation rates and patterns, effective population sizes, rates of recombination and biased gene conversion, and the fitness effects of mutations. Strict constancy of all these factors is implausible. However, the timescale of parameter fluctuations determines their relevance to molecular evolution; variability in evolutionary forces cause heterogeneous substitution patterns if parameters changes occur on a similar timescale as molecular evolution (Gillespie 1993(Gillespie , 1994 Cutler 2000a,b). Although theoretical concerns suggest that appropriately scaled parameter fluctuations should not be common, numerous studies have invoked nonstationarity to explain variable rates of protein evolution at particular loci or in specific lineages. These include fluctuations in neutral mutation rates (Fitch and Markowitz 1970;Fitch 1971;Takahata 1987), effective population sizes (e.g., Oht...

Evolution of genes and genomes on the Drosophila phylogeny

“…We found evidence for a lineagespecific genomic reduction in codon bias in D. melanogaster (Fig. 5), as has been suggested previously [113][114][115][116][117][118][119] . In addition, maximum-likelihood estimation of the strength of selection on synonymous sites in 8,510 melanogaster group single-copy orthologues revealed a marked reduction in the number of genes under selection for increased codon bias in D. melanogaster relative to its sister species D. sechellia 120 .…”

Patterns of Molecular Variation and Evolution in Drosophila americana and Its Relatives

“…For six codons, alternative paths implied different numbers of synonymous and nonsynonymous changes. For a similar data set, Akashi et al (2006) showed that, given sufficiently low numbers of substitutions per site, this method gives similar results to those obtained when a correction for synonymous/nonsynonymous ratios is used to weight alternative paths. Codons that had changes at all three positions were excluded from the data set.…”

“…Probabilities of ancestral codons were calculated as the product of the probabilities of ancestral nucleotides at each codon position (Akashi et al 2006). When ancestral and derived codons differed by a single nucleotide, the probability of the ancestral codon was taken as the change's count.…”

“…Assuming equilibrium for codon usage, an equal number of changes in either direction is expected. Departures from equilibrium were quantified as d UPÀPU ¼ (UP À PU)/(UP 1 PU), which has a range of À1 to 1 (Akashi et al 2006). The significance of any departures was assessed by means of the Wilcoxon signed-rank test (WSR), which compares UP with PU mutation counts per locus on each lineage.…”

The Hill–Robertson effect: evolutionary consequences of weak selection and linkage in finite populations

“…In D. melanogaster, the correlation between recombination rate and either codon bias or noncoding G þ C content is not observed in regions with very high recombination rates (Kliman and Hey, 2003) and substitution rates at noncoding regions are not reduced in regions with high recombination (Singh et al, 2005). Altogether, these observations are more consistent with a relaxation of long-range HR effects in regions of high recombination coupled with a recent increase in mutational biases toward AT (Kern and Begun, 2005;Akashi et al, 2006).…”