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Open Access Open Badges Research article

Correlates of substitution rate variation in mammalian protein-coding sequences

John J Welch12*, Olaf RP Bininda-Emonds3 and Lindell Bromham24

Author Affiliations

1 Institute of Evolutionary Biology; School of Biological Sciences; University of Edinburgh, West Mains Rd., Edinburgh EH9 3JT, UK

2 Centre for the Study of Evolution; School of Life Sciences; University of Sussex, Falmer, Brighton BN1 9QG, UK

3 Institut für Spezielle Zoologie und Evolutionsbiologie mit Phyletischem Museum; Friedrich-Schiller-Universität Jena, Erbertstrasse 1, 07743 Jena, Germany

4 Centre for Macroevolution and Macroecology; School of Botany and Zoology; Australian National University, Canberra, A.C.T. 0200, Australia

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BMC Evolutionary Biology 2008, 8:53  doi:10.1186/1471-2148-8-53

Published: 19 February 2008



Rates of molecular evolution in different lineages can vary widely, and some of this variation might be predictable from aspects of species' biology. Investigating such predictable rate variation can help us to understand the causes of molecular evolution, and could also help to improve molecular dating methods. Here we present a comprehensive study of the life history correlates of substitution rate variation across the mammals, comparing results for mitochondrial and nuclear loci, and for synonymous and non-synonymous sites. We use phylogenetic comparative methods, refined to take into account the special nature of substitution rate data. Particular attention is paid to the widespread correlations between the components of mammalian life history, which can complicate the interpretation of results.


We find that mitochondrial synonymous substitution rates, estimated from the 9 longest mitochondrial genes, show strong negative correlations with body mass and with maximum recorded lifespan. But lifespan is the sole variable to remain after multiple regression and model simplification. Nuclear synonymous substitution rates, estimated from 6 genes, show strong negative correlations with body mass and generation time, and a strong positive correlation with fecundity. In contrast to the mitochondrial results, the same trends are evident in rates of nonsynonymous substitution.


A substantial proportion of variation in mammalian substitution rates can be explained by aspects of their life history, implying that molecular and life history evolution are closely interlinked in this group. The strength and consistency of the nuclear body mass effect suggests that molecular dating studies may have been systematically misled, but also that methods could be improved by incorporating the finding as a priori information. Mitochondrial synonymous rates also show the body mass effect, but for apparently quite different reasons, and the strength of the relationship with maximum lifespan provides support for the hypothesis that mtDNA damage is causally linked to aging.