X-linked genes evolve higher codon bias in Drosophila and Caenorhabditis

Abstract

Comparing patterns of molecular evolution between autosomes and sex chromosomes (such as X and W chromosomes) can provide insight into the forces underlying genome evolution. Here we investigate patterns of codon bias evolution on the X chromosome and autosomes in Drosophila and Caenorhabditis. We demonstrate that X-linked genes have significantly higher codon bias compared to autosomal genes in both Drosophila and Caenorhabditis. Furthermore, genes that become X-linked evolve higher codon bias gradually, over tens of millions of years. We provide several lines of evidence that this elevation in codon bias is due exclusively to their chromosomal location and not to any other property of X-linked genes. We present two possible explanations for these observations. One possibility is that natural selection is more efficient on the X chromosome due to effective haploidy of the X chromosomes in males and persistently low effective numbers of reproducing males compared to that of females. Alternatively, X-linked genes might experience stronger natural selection for higher codon bias as a result of maladaptive reduction of their dosage engendered by the loss of the Y-linked homologs.

Figure 1.

Optimal codon frequencies on each chromosome in (a) D. melanogaster, (b) D. pseudoobscura, and (c) C. elegans. Error bars denote standard error.

Figure 2.

Optimal codon frequencies on the autosomes (dark shading) and on the X chromosome (light shading) in (a) D. melanogaster and (b) C. elegans. For partitioned data, genes were split on the median value of a given parameter on the X chromosome; this cutoff was then also applied to the autosomal genes. Error bars denote standard error. In D. melanogaster, short proteins were those encoded by ≤394 amino acids, low recombination was defined as ≤3.48 cM/Mb, and low K_a was defined as ≤0.07945. Lowly expressed genes were those with three or fewer EST counts, and gonad-biased expression is defined as genes exceeding a twofold difference in log-ratio of expression between testes and ovaries of adult flies. Comparisons between the X and the autosomes for male- and female-biased genes are significant (P = 0.03 and 0.02, respectively, one-tailed t-test), while all other comparisons are highly significant (P ≪ 0.0001, all comparisons, one-tailed t-test). The numbers of genes included in partitions by length, recombination, K_a, gonad-biased expression, absolute expression, and gene density are 12,444, 12,444, 7335, 1783, 10,202, and 12,368, respectively. In C. elegans, short proteins were those encoded by ≤396 amino acids, low recombination was defined as ≤2.66 cM/Mb, and low K_a was defined as ≤0.113. Lowly expressed genes were those with two or fewer SAGE counts. Differences in codon usage between the X and the autosomes for genes in areas of high recombination and genes with low K_a are not statistically significant (P = 0.48 and 0.14, respectively, one-tailed t-test), while all other comparisons are highly significant (P < 0.0001, all comparisons, one-tailed t-test). The numbers of genes included in partitions by length, recombination, K_a, expression, and gene density are 18,476, 18,476, 10,157, 2988, and 18,442, respectively.

Figure 3.

Optimal codon frequencies of duplicate gene pairs in D. melanogaster and C. elegans. Optimal codon frequencies of the autosomal members of the duplicate pair are shown with dark shading, while light shading corresponds to optimal codon frequencies in the X-linked paralog. Error bars denote standard error.

Figure 4.

Optimal codon frequencies in orthologous genes of D. melanogaster and D. pseudoobscura. Dark shading denotes genes in D. pseudoobscura and light shading shows their orthologs in D. melanogaster. “Autosome” genes are mapped to the autosomes of both species, “XL vs. X” genes are mapped to XL in D. pseudoobscura and X in D. melanogaster, and “XR vs. 3L” genes are mapped to XR in D. pseudoobscura and 3L in D. melanogaster. Error bars denote standard error.

Figure 5.

Frequency of optimal codons in X-linked and autosomal genes with optimal codon frequencies in highly vs. lowly expressed genes for comparison in (a) D. melanogaster and (b) C. elegans.

Figure 6.

Values of c (N_M/N_F) and F (s₁/s₂) for which R(x) > 1 (shaded area) and <1 (open area). The dashed line represents pairs of F and c that correspond to the observed difference in codon bias between X-linked an autosomal genes assuming the probability of mutation away from a preferred codon is three times the probability of mutation to the preferred codon (see supplementary materials at http://www.genetics.org/supplemental/).