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Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7853-7. doi: 10.1073/pnas.0911249107. Epub 2010 Apr 12.

Contrasts between adaptive coding and noncoding changes during human evolution.

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Biology Department and Institute for Genome Sciences and Policy, Duke University, Durham, NC 27708, USA.


Changes in non-protein-coding regulatory DNA sequences have been proposed to play distinctive roles in adaptive evolution. We analyzed correlations between gene functions and evidence for positive selection in a common statistical framework across several large surveys of coding and noncoding sequences throughout the human genome. Strong correlations with both classifications in gene ontologies and measurements of gene expression indicate that neural development and function have adapted mainly through noncoding changes. In contrast, adaptation via coding changes is dominated by immunity, olfaction, and male reproduction. Genes with highly tissue-specific expression have undergone more adaptive coding changes, suggesting that pleiotropic constraints inhibit such changes in broadly expressed genes. In contrast, adaptive noncoding changes do not exhibit this pattern. Our findings underscore the probable importance of noncoding changes in the evolution of human traits, particularly cognitive traits.

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