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Correlates of substitution rate variation in mammalian protein-coding sequences.

Welch JJ, Bininda-Emonds OR, Bromham L - BMC Evol. Biol. (2008)

Bottom Line: Particular attention is paid to the widespread correlations between the components of mammalian life history, which can complicate the interpretation of results.In contrast to the mitochondrial results, the same trends are evident in rates of nonsynonymous substitution.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, West Mains Rd., Edinburgh EH9 3JT, UK. j.j.welch@ed.ac.uk

ABSTRACT

Background: 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.

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.

Conclusion: 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.

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Mitochondrial results. Plots of mitochondrial synonymous substitution rate (expected substitutions per site per million years), against body mass in grammes (a-b), and maximum recorded lifespan in months (c-d). Substitution rates were estimated from a concatenated alignment of nine loci. Shown are phylogenetically-independent comparisons, (a) and (c), with the best-fit regression line forced through the origin, and the raw cross-species values (b) and (d), with lineages excluded from the independent comparisons analysis shown as empty circles. For the independent comparisons, trait measurements were log transformed, and contrasts standardised with their expected standard deviation [see Additional file 2]. (e) and (f) show body mass results for the Euarchontoglires, a subset of the data in (a) and (b).
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Figure 1: Mitochondrial results. Plots of mitochondrial synonymous substitution rate (expected substitutions per site per million years), against body mass in grammes (a-b), and maximum recorded lifespan in months (c-d). Substitution rates were estimated from a concatenated alignment of nine loci. Shown are phylogenetically-independent comparisons, (a) and (c), with the best-fit regression line forced through the origin, and the raw cross-species values (b) and (d), with lineages excluded from the independent comparisons analysis shown as empty circles. For the independent comparisons, trait measurements were log transformed, and contrasts standardised with their expected standard deviation [see Additional file 2]. (e) and (f) show body mass results for the Euarchontoglires, a subset of the data in (a) and (b).

Mentions: The single variable regressions, summarised in Table 1, show that of the four variables tested, body mass and maximum lifespan are individually significant predictors of mitochondrial synonymous substitution rates: Species with greater mass, or longer lifespan tend to have slower rates of synonymous substitution. The significant regressions are plotted in Figure 1a–d, together with their associated raw cross-species plots, which show closely similar trends. A multiple regression analysis, including pairs with measurements for all four predictor traits, shows that only maximum lifespan remains significant (Table 2). Furthermore, model simplification shows that lifespan alone explains almost as much variation as does the four-predictor model (Table 2). Table 3 contains results for the larger subset of points for which lifespan and body mass measurements were available (i.e., including those pairs lacking fecundity or generation time data). Again, maximum lifespan was found to be the sole significant predictor. Diagnostic tests identified the sperm whale pair, Kogia breviceps-Physeter catodon, as a weak outlier, and excluding this pair increases the r2 to levels matching those in Table 2. (It is possible that the outlying nature of this point reflects the recognised difficulties obtaining accurate measurements of maximum lifespan for cetaceans: [47].)


Correlates of substitution rate variation in mammalian protein-coding sequences.

Welch JJ, Bininda-Emonds OR, Bromham L - BMC Evol. Biol. (2008)

Mitochondrial results. Plots of mitochondrial synonymous substitution rate (expected substitutions per site per million years), against body mass in grammes (a-b), and maximum recorded lifespan in months (c-d). Substitution rates were estimated from a concatenated alignment of nine loci. Shown are phylogenetically-independent comparisons, (a) and (c), with the best-fit regression line forced through the origin, and the raw cross-species values (b) and (d), with lineages excluded from the independent comparisons analysis shown as empty circles. For the independent comparisons, trait measurements were log transformed, and contrasts standardised with their expected standard deviation [see Additional file 2]. (e) and (f) show body mass results for the Euarchontoglires, a subset of the data in (a) and (b).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2289806&req=5

Figure 1: Mitochondrial results. Plots of mitochondrial synonymous substitution rate (expected substitutions per site per million years), against body mass in grammes (a-b), and maximum recorded lifespan in months (c-d). Substitution rates were estimated from a concatenated alignment of nine loci. Shown are phylogenetically-independent comparisons, (a) and (c), with the best-fit regression line forced through the origin, and the raw cross-species values (b) and (d), with lineages excluded from the independent comparisons analysis shown as empty circles. For the independent comparisons, trait measurements were log transformed, and contrasts standardised with their expected standard deviation [see Additional file 2]. (e) and (f) show body mass results for the Euarchontoglires, a subset of the data in (a) and (b).
Mentions: The single variable regressions, summarised in Table 1, show that of the four variables tested, body mass and maximum lifespan are individually significant predictors of mitochondrial synonymous substitution rates: Species with greater mass, or longer lifespan tend to have slower rates of synonymous substitution. The significant regressions are plotted in Figure 1a–d, together with their associated raw cross-species plots, which show closely similar trends. A multiple regression analysis, including pairs with measurements for all four predictor traits, shows that only maximum lifespan remains significant (Table 2). Furthermore, model simplification shows that lifespan alone explains almost as much variation as does the four-predictor model (Table 2). Table 3 contains results for the larger subset of points for which lifespan and body mass measurements were available (i.e., including those pairs lacking fecundity or generation time data). Again, maximum lifespan was found to be the sole significant predictor. Diagnostic tests identified the sperm whale pair, Kogia breviceps-Physeter catodon, as a weak outlier, and excluding this pair increases the r2 to levels matching those in Table 2. (It is possible that the outlying nature of this point reflects the recognised difficulties obtaining accurate measurements of maximum lifespan for cetaceans: [47].)

Bottom Line: Particular attention is paid to the widespread correlations between the components of mammalian life history, which can complicate the interpretation of results.In contrast to the mitochondrial results, the same trends are evident in rates of nonsynonymous substitution.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, West Mains Rd., Edinburgh EH9 3JT, UK. j.j.welch@ed.ac.uk

ABSTRACT

Background: 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.

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus