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Natural selection drives rapid evolution of mouse embryonic heart enhancers.

ABSTRACT: BACKGROUND: Mouse E11.5 embryonic heart enhancers were found to exhibit exceptionally weak sequence conservation during vertebrate evolution compared to enhancers of other developing organs. However, it is unknown whether this phenomenon is due to elevated mutation rates, or is a consequence of natural selection. RESULTS: In this study, based on the aligned orthologous genomic sequences of mouse and other closely related mammals, the substitution rates of fourfold degenerate sites or intron sequences in neighboring genes were used as neutral references to normalize substitution rates of mouse enhancers. Subsequent comparisons indicated that heart enhancers' evolutionary rates were increased by natural selection. Correspondingly, the results of Fisher's exact tests to examine the differential enrichment of substitutions between enhancers and neutral sequences suggest that both relaxed purifying selection and positive selection caused the rapid evolution of heart enhancers. Analyses on recombination rates and substitution patterns indicated that GC-biased gene conversion does not contribute to evolutionary rate variations among enhancers. In general, pleiotropic enhancers and enhancers in proximity to weakly expressed genes, tend to evolve slowly. Although heart enhancers are less pleiotropic and are adjacent to highly expressed genes, these biases do not account for the rapid evolution observed. CONCLUSIONS: In combination, the results of the present study suggest that factors associated with functions or characteristics of the tissue may exert direct and profound effects on the intensity and direction of the natural selection applied to regulatory DNAs, such as enhancers.

SUBMITTER: Liao BY

PROVIDER: S-EPMC3521173 | biostudies-other | 2012

REPOSITORIES: biostudies-other

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Natural selection drives rapid evolution of mouse embryonic heart enhancers.

Liao Ben-Yang BY Weng Meng-Pin MP

BMC systems biology 20121212

<h4>Background</h4>Mouse E11.5 embryonic heart enhancers were found to exhibit exceptionally weak sequence conservation during vertebrate evolution compared to enhancers of other developing organs. However, it is unknown whether this phenomenon is due to elevated mutation rates, or is a consequence of natural selection.<h4>Results</h4>In this study, based on the aligned orthologous genomic sequences of mouse and other closely related mammals, the substitution rates of fourfold degenerate sites o ...[more]

PMID: 23281795

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Project description:Mitochondria play a key role in the balance of energy and heat production, and therefore the mitochondrial genome is under natural selection by environmental temperature and food availability, since starvation can generate more efficient coupling of energy production. However, selection over mitochondrial DNA (mtDNA) genes has usually been evaluated at the population level. We sequenced by NGS 12 mitogenomes and with four published genomes, assessed genetic variation in ten penguin species distributed from the equator to Antarctica. Signatures of selection of 13 mitochondrial protein-coding genes were evaluated by comparing among species within and among genera (Spheniscus, Pygoscelis, Eudyptula, Eudyptes and Aptenodytes). The genetic data were correlated with environmental data obtained through remote sensing (sea surface temperature [SST], chlorophyll levels [Chl] and a combination of SST and Chl [COM]) through the distribution of these species.We identified the complete mtDNA genomes of several penguin species, including ND6 and 8 tRNAs on the light strand and 12 protein coding genes, 14 tRNAs and two rRNAs positioned on the heavy strand. The highest diversity was found in NADH dehydrogenase genes and the lowest in COX genes. The lowest evolutionary divergence among species was between Humboldt (Spheniscus humboldti) and Galapagos (S. mendiculus) penguins (0.004), while the highest was observed between little penguin (Eudyptula minor) and Adélie penguin (Pygoscelis adeliae) (0.097). We identified a signature of purifying selection (Ka/Ks?<?1) across the mitochondrial genome, which is consistent with the hypothesis that purifying selection is constraining mitogenome evolution to maintain Oxidative phosphorylation (OXPHOS) proteins and functionality. Pairwise species maximum-likelihood analyses of selection at codon sites suggest positive selection has occurred on ATP8 (Fixed-Effects Likelihood, FEL) and ND4 (Single Likelihood Ancestral Counting, SLAC) in all penguins. In contrast, COX1 had a signature of strong negative selection. ND4 Ka/Ks ratios were highly correlated with SST (Mantel, p-value: 0.0001; GLM, p-value: 0.00001) and thus may be related to climate adaptation throughout penguin speciation.These results identify mtDNA candidate genes under selection which could be involved in broad-scale adaptations of penguins to their environment. Such knowledge may be particularly useful for developing predictive models of how these species may respond to severe climatic changes in the future.

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Natural selection drives rapid evolution of mouse embryonic heart enhancers.

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Natural selection drives rapid evolution of mouse embryonic heart enhancers.

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