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Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3215-20. doi: 10.1073/pnas.0712400105. Epub 2008 Feb 27.

Distinct genomic signatures of adaptation in pre- and postnatal environments during human evolution.

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  • 1Center for Molecular Medicine and Genetics and Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA.

Abstract

The human genome evolution project seeks to reveal the genetic underpinnings of key phenotypic features that are distinctive of humans, such as a greatly enlarged cerebral cortex, slow development, and long life spans. This project has focused predominantly on genotypic changes during the 6-million-year descent from the last common ancestor (LCA) of humans and chimpanzees. Here, we argue that adaptive genotypic changes during earlier periods of evolutionary history also helped shape the distinctive human phenotype. Using comparative genome sequence data from 10 vertebrate species, we find a signature of human ancestry-specific adaptive evolution in 1,240 genes during their descent from the LCA with rodents. We also find that the signature of adaptive evolution is significantly different for highly expressed genes in human fetal and adult-stage tissues. Functional annotation clustering shows that on the ape stem lineage, an especially evident adaptively evolved biological pathway contains genes that function in mitochondria, are crucially involved in aerobic energy production, and are highly expressed in two energy-demanding tissues, heart and brain. Also, on this ape stem lineage, there was adaptive evolution among genes associated with human autoimmune and aging-related diseases. During more recent human descent, the adaptively evolving, highly expressed genes in fetal brain are involved in mediating neuronal connectivity. Comparing adaptively evolving genes from pre- and postnatal-stage tissues suggests that different selective pressures act on the development vs. the maintenance of the human phenotype.

PMID:
18305157
[PubMed - indexed for MEDLINE]
PMCID:
PMC2265188
Free PMC Article

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