Extensive evolutionary changes in regulatory element activity during human origins are associated with altered gene expression and positive selection. PLoS Genet. 2012
Sunday, April 12th, 2015Changes in [DHS] #regulatory element activity…[over 3 primates] associated w/ altered…expression & pos. selection
http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1002789
DHS across 3 primates finds species specific sites associated with differential expression & positive selection
Shibata Y, Sheffield NC, Fedrigo O, Babbitt CC, Wortham M, Tewari AK, London D, Song L, Lee BK, Iyer VR, Parker SC, Margulies EH, Wray GA, Furey TS, Crawford GE*. Extensive evolutionary changes in regulatory element activity during human origins are
associated with altered gene expression and positive selection. PLoS Genet. 2012 Jun; 8(6):e1002789. doi: 10.1371/journal.pgen.1002789. Epub 2012 Jun 28. PubMed PMID: 22761590; PubMed Central PMCID: PMC3386175
SUMMARY (from csds):
The study is focused on analyzing genotype-phenotype correlation by looking at the evolution of DHS sites across three primate genomes: human, chimp and macaque. By comparing the data they were able to identify common DHS sites across the three species (sites that show similar DHS levels) and also species-specific sites. All the assays were supported by ChiP experiments. The study identified >2000 regulatory elements that were gained/lost since the divergence of
human and chimp. Looking at DNase and RNAseq data the authors show that the enrichment of regulatory elements next to genes with species-specific expression, suggests that the gain or loss of DHS sites impacts transcript abundance. The human DHS sites were enhanced for chromatin marks predictive of enhancers, while common regions were preferentially associated with promoters and insulators. By looking at species specificity, they found that species-specific DHS gains are cell type specific while both species specific DHS gains and losses are subject to positive selection. The common DHS sites are conserved and are suggested to have roles involving transcription and general housekeeping.