Publication Date:
2012-09-26
Description:
From studies investigating the differences in evolutionary rates between genes, gene compactness and gene expression level have been identified as important determinants of gene-level protein evolutionary rate, as represented by nonsynonymous to synonymous substitution rate ( d N / d S ) ratio. However, the causes of exon-level variances in d N / d S are less understood. Here, we use principal component regression to examine to what extent 13 exon features explain the variance in d N , d S , and the d N / d S ratio of human–rhesus macaque or human–mouse orthologous exons. The exon features were grouped into six functional categories: expression features, mRNA splicing features, structural–functional features, compactness features, exon duplicability, and other features, including G + C content and exon length. Although expression features are important for determining d N and d N / d S between exons of different genes, structural–functional features and splicing features explained more of the variance for exons of the same genes. Furthermore, we show that compactness features can explain only a relatively small percentage of variance in exon-level d N or d N / d S in either between-gene or within-gene comparison. By contrast, d S yielded inconsistent results in the human–mouse comparison and the human–rhesus macaque comparison. This inconsistency may suggest rapid evolutionary changes of the mutation landscape in mammals. Our results suggest that between-gene and within-gene variation in d N / d S (and d N ) are driven by different evolutionary forces and that the role of mRNA splicing in causing the variation in evolutionary rates of coding sequences may be underappreciated.
Print ISSN:
0737-4038
Electronic ISSN:
1537-1719
Topics:
Biology
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