Saturday, September 14, 2013

Significance of Methylation in Divergence among Great Apes

In the September 5th issue of PLoS Genetics, Hernando-Herraez et al. present findings from a comparative study of CpG methylation patterns in great apes. The researchers generated methylation profiles from peripheral blood samples from nine humans, five chimpanzees, six bonobos, six gorillas, and six orangutans using the Illumina HumanMethylation platform. Notably, the authors found that great ape phylogeny could be recovered based on degree of divergence in methylation patterns. They were further able to identify many genes with lineage-specific methylation patters for all species, as well as enrichment for genes of species-specific functional categories. For example, in the case of humans, 171 uniquely methylated genes were identified showing enrichment related to neurological function and facial development. In particular, genes involved in semi-circular canal development in the inner ear were enriched for methylation in humans. This is especially interesting given the implication of this feature in maintaining balance during bipedal locomotion. 

Hernando-Herraez et al. further focused in on human-chimp differences by undertaking a pairwise comparison of a expanded dataset for the two species. Interestingly, they found that genes showing divergence in protein coding sequences were likely to also be differentially methylated, suggesting that molecular evolution may often combine sequence change and epigenetic change. However, they were also able to identify 184 genes that were conserved at the protein level between humans and chimps, but showed significant differences in promotor methylation, lending support to the frequently-invoked hypothesis that a substantial degree of phenotypic evolution along the chimpanzee and human lines is underlain by regulatory changes rather than changes at the protein level (King and Wilson, 1975; Ohno, 1971).

Hernando-Herraez I, Gilad Y, Prado-Martinez J, Garg P, Fernandez-Callejo M, Heyn H, Hvilsom C, Navarro A, Esteller M, Sharp A J and Marques-Bonet, T (2013). Dynamics of DNA Methylation in Recent Human and Great Ape Evolution. PLoS Genetics 9(9):e1003763.
King M and Wilson A (1975). Evolution at two levels in humans and chimpanzees. Science 188(4184):107-16.
Ohno, S (1971). Simplicity of mammalian regulatory systems inferred by single gene determination of sex phenotypes. Nature 234:134-137.

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