Transcription-Associated Compositional Skews in Drosophila Genes

Abstract

In many organisms, local deviations from Chargaff's second parity rule are observed around replication and transcription start sites and within intron sequences. Here, we use expression data as well as a whole-genome data set of nearly 200 haplotypes to investigate such compositional skews in Drosophila melanogaster genes. We find a positive correlation between compositional skew and gene expression, comparable in strength to similar correlations between expression levels and genome-wide sequence features. This correlation is relatively stronger for germline, compared with somatic expression, consistent with the process of transcription-associated mutation bias. We also inferred mutation rates from alleles segregating at low frequencies in short introns, and show that, whereas the overall GC content of short introns does not conform to the equilibrium expectation, the level of the observed deviation from the second parity rule is generally consistent with the inferred rates.

Keywords: Chargaff’s second parity rule; base composition evolution; compositional skew; transcription-associated mutation bias.

Fig. 1.

—Pearson’s coefficients (with 95% CIs) for the correlations between compositional skew and gene expression across different tissues and developmental stages. (A–C) Correlation of CG skew and gene expression. (D–F) Correlation of TA skew and gene expression. Although 0- to 2-h expression in embryos most likely reflects maternal transcription, which should not necessarily affect germline development, the correlation between maternal expression and later putative zygotic expression (2–4 h) is strong (Spearman’s ρ = 0.937, P < 0.001).

Fig. 2.

—Distributions of skew estimates and nucleotide content obtained from 10,000 independent parameter search runs, conditional on the observed compositional skew in autosomal short introns and the 95% CIs of mutation rates in table 1. (A and B) Distributions of CG and TA skew, respectively; the red dashed line is the observed skew level. (C) The distribution of G (red) and C (black) content; the dashed lines are the observed values. (D) The distribution of A (red) and T (black) content; the dashed lines are the observed values.