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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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Nuclear results. Plots of nuclear synonymous substitution rate against body mass (a-b), maximum recorded lifespan (c-d), generation time (e-f), and fecundity (g-h). Substitution rates were estimated from a concatenated alignment of six loci. Two species with outlying lifespan values are shown as asterisks in (c) and (d), and (c) includes the regression lines for both the complete set of points (solid line), and with these two outlying values excluded (dashed line). All other details are as for Figure 1.
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Figure 2: Nuclear results. Plots of nuclear synonymous substitution rate against body mass (a-b), maximum recorded lifespan (c-d), generation time (e-f), and fecundity (g-h). Substitution rates were estimated from a concatenated alignment of six loci. Two species with outlying lifespan values are shown as asterisks in (c) and (d), and (c) includes the regression lines for both the complete set of points (solid line), and with these two outlying values excluded (dashed line). All other details are as for Figure 1.

Mentions: Plots for the nuclear synonymous data set are shown in Figure 2. Table 1 shows that body mass, generation time and fecundity are all significant predictors of nuclear synonymous rates. Lifespan, by contrast, shows no trend, but this is attributable to two clear outliers, appearing as such in both the diagnostic tests of the regressions (Fig. 2c) and in the raw cross-species scatter-plots (Fig. 2d). (The two small values are for Cynocephalus variegatus, the malayan flying lemur, and Amblysomus hottentotus, the hottentot golden mole). Removing these two outlying points makes maximum lifespan, too, a significant predictor of synonymous rates (Table 1). Of course, these outliers could represent true biological variation, but problems with maximum recorded lifespan as a statistic make measurement error particularly likely in this case [13,22,47,48]. (For example, recorded lifespan can only increase with new observations, and so is strongly dependent on the number of animals sampled; a species' suitability for captivity will also have an important influence.) If outliers are excluded, then for each of the predictors, r2 values are much higher than for the mitochondrial data set, even when corrections for reduced sample size are made. Furthermore, and again in contrast to the mitochondrial results, all effects apply consistently to Laurasiatheria and Euarchontoglires (the nuclear data set contains no Metatheria).


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

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

Nuclear results. Plots of nuclear synonymous substitution rate against body mass (a-b), maximum recorded lifespan (c-d), generation time (e-f), and fecundity (g-h). Substitution rates were estimated from a concatenated alignment of six loci. Two species with outlying lifespan values are shown as asterisks in (c) and (d), and (c) includes the regression lines for both the complete set of points (solid line), and with these two outlying values excluded (dashed line). All other details are as for Figure 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Nuclear results. Plots of nuclear synonymous substitution rate against body mass (a-b), maximum recorded lifespan (c-d), generation time (e-f), and fecundity (g-h). Substitution rates were estimated from a concatenated alignment of six loci. Two species with outlying lifespan values are shown as asterisks in (c) and (d), and (c) includes the regression lines for both the complete set of points (solid line), and with these two outlying values excluded (dashed line). All other details are as for Figure 1.
Mentions: Plots for the nuclear synonymous data set are shown in Figure 2. Table 1 shows that body mass, generation time and fecundity are all significant predictors of nuclear synonymous rates. Lifespan, by contrast, shows no trend, but this is attributable to two clear outliers, appearing as such in both the diagnostic tests of the regressions (Fig. 2c) and in the raw cross-species scatter-plots (Fig. 2d). (The two small values are for Cynocephalus variegatus, the malayan flying lemur, and Amblysomus hottentotus, the hottentot golden mole). Removing these two outlying points makes maximum lifespan, too, a significant predictor of synonymous rates (Table 1). Of course, these outliers could represent true biological variation, but problems with maximum recorded lifespan as a statistic make measurement error particularly likely in this case [13,22,47,48]. (For example, recorded lifespan can only increase with new observations, and so is strongly dependent on the number of animals sampled; a species' suitability for captivity will also have an important influence.) If outliers are excluded, then for each of the predictors, r2 values are much higher than for the mitochondrial data set, even when corrections for reduced sample size are made. Furthermore, and again in contrast to the mitochondrial results, all effects apply consistently to Laurasiatheria and Euarchontoglires (the nuclear data set contains no Metatheria).

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