TY - JOUR

T1 - Codon usage bias and effective population sizes on the X chromosome versus the autosomes in Drosophila melanogaster

AU - Campos, Jose L

AU - Zeng, Kai

AU - Parker, Darren J

AU - Charlesworth, Brian

AU - Haddrill, Penelope R

PY - 2013/4/1

Y1 - 2013/4/1

N2 - Codon usage bias (CUB) in Drosophila is higher for X-linked genes than for autosomal genes. One possible explanation is that the higher effective recombination rate for genes on the X chromosome compared with the autosomes reduces their susceptibility to Hill-Robertson effects, and thus enhances the efficacy of selection on codon usage. The genome sequence of D. melanogaster was used to test this hypothesis. Contrary to expectation, it was found that, after correcting for the effective recombination rate, CUB remained higher on the X than on the autosomes. In contrast, an analysis of polymorphism data from a Rwandan population showed that mean nucleotide site diversity at 4-fold degenerate sites for genes on the X is approximately three-quarters of the autosomal value after correcting for the effective recombination rate, compared with approximate equality before correction. In addition, these data show that selection for preferred versus unpreferred synonymous variants is stronger on the X than the autosomes, which accounts for the higher CUB of genes on the X chromosome. This difference in the strength of selection does not appear to reflect the effects of dominance of mutations affecting codon usage, differences in gene expression levels between X and autosomes, or differences in mutational bias. Its cause therefore remains unexplained. The stronger selection on CUB on the X chromosome leads to a lower rate of synonymous site divergence compared with the autosomes; this will cause a stronger upward bias for X than A in estimates of the proportion of nonsynonymous mutations fixed by positive selection, for methods based on the McDonald-Kreitman test.

AB - Codon usage bias (CUB) in Drosophila is higher for X-linked genes than for autosomal genes. One possible explanation is that the higher effective recombination rate for genes on the X chromosome compared with the autosomes reduces their susceptibility to Hill-Robertson effects, and thus enhances the efficacy of selection on codon usage. The genome sequence of D. melanogaster was used to test this hypothesis. Contrary to expectation, it was found that, after correcting for the effective recombination rate, CUB remained higher on the X than on the autosomes. In contrast, an analysis of polymorphism data from a Rwandan population showed that mean nucleotide site diversity at 4-fold degenerate sites for genes on the X is approximately three-quarters of the autosomal value after correcting for the effective recombination rate, compared with approximate equality before correction. In addition, these data show that selection for preferred versus unpreferred synonymous variants is stronger on the X than the autosomes, which accounts for the higher CUB of genes on the X chromosome. This difference in the strength of selection does not appear to reflect the effects of dominance of mutations affecting codon usage, differences in gene expression levels between X and autosomes, or differences in mutational bias. Its cause therefore remains unexplained. The stronger selection on CUB on the X chromosome leads to a lower rate of synonymous site divergence compared with the autosomes; this will cause a stronger upward bias for X than A in estimates of the proportion of nonsynonymous mutations fixed by positive selection, for methods based on the McDonald-Kreitman test.

KW - Animals

KW - Base Composition

KW - Chromosomes, Insect/genetics

KW - Codon

KW - Drosophila Proteins/genetics

KW - Drosophila melanogaster/genetics

KW - Female

KW - Gene Expression

KW - Genes, X-Linked

KW - Genetic Variation

KW - Male

KW - Models, Genetic

KW - Open Reading Frames

KW - Population Density

KW - Recombination, Genetic

KW - Selection, Genetic

KW - X Chromosome/genetics

U2 - 10.1093/molbev/mss222

DO - 10.1093/molbev/mss222

M3 - Article

C2 - 23204387

VL - 30

SP - 811

EP - 823

JO - Molecular Biology and Evolution

JF - Molecular Biology and Evolution

SN - 0737-4038

IS - 4

ER -