The signature of selection mediated by expression on human genes

Abstract

As the efficacy of natural selection is expected to be a function of population size, in humans it is usually presumed that selection is a weak force and hence that gene characteristics are mostly determined by stochastic forces. In contrast, in species with large population sizes, selection is expected to be a much more effective force. Evidence for this has come from examining how genic parameters vary with expression level, which appears to determine many of a gene's features, such as codon bias, amino acid composition, and size. However, not until now has it been possible to examine whether human genes show the signature of selection mediated by expression level. Here, then, to investigate this issue, we gathered expression data for >10,000 human genes from public data sets obtained by different technologies (SAGE and high-density oligonucleotide chip arrays) and compared them with gene parameters. We find that, even after controlling for regional effects, highly expressed genes code for smaller proteins, have less intronic DNA, and higher codon and amino acid biases. We conclude that, contrary to the usual supposition, human genes show signatures consistent with selection mediated by expression level.

Figure 1

Intron content and expression level in human genes. Genes were split into 10 groups of an equal number of cases according to expression level. White dots represent the mean expression value for each group. Black boxes and error bars show the standard error with 68% and 95% of confidence.

Figure 2

Codon bias (MCB) and level of expression. Codon usage bias MCB after correcting for background nucleotide content. Genes were split into 10 groups of an equal number of cases according to expression level. White dots represent the mean expression value for each group. Black boxes and error bars show the standard error with 68% and 95% of confidence.