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Human accelerated regions (HARs), first described in August 2006,[1][2] are a set of 49 segments of the human genome that are conserved throughout vertebrate evolution but are strikingly different in humans. They are named according to their degree of difference between humans and chimpanzees (HAR1 showing the largest degree of human-chimpanzee differences). Found by scanning through genomic databases of multiple species, some of these highly mutated areas may contribute to human-specific traits. Others may represent loss of functional mutations, possibly due to the action of biased gene conversion[2][3] rather than adaptive evolution.[4][5][6]
Characterisation of HAR1-HAR5 regions, from a paper on Forces shaping the fastest evolving regions in the human genome by Katherine Pollard et al.[2]
Several of the HARs encompass genes known to produce proteins important in neurodevelopment. HAR1 is a 106-base pair stretch found on the long arm of chromosome 20 overlapping with part of the RNA genes HAR1F and HAR1R. HAR1F is active in the developing human brain. The HAR1 sequence is found (and conserved) in chickens and chimpanzees but is not present in fish or frogs that have been studied. There are 18 base pair mutations different between humans and chimpanzees, far more than expected by its history of conservation.[1]
HAR2 includes HACNS1 a gene enhancer "that may have contributed to the evolution of the uniquely opposable human thumb, and possibly also modifications in the ankle or foot that allow humans to walk on two legs". Evidence to date shows that of the 110,000 gene enhancer sequences identified in the human genome, HACNS1 has undergone the most change during the evolution of humans following the split with the ancestors of chimpanzees.[7] The substitutions in HAR2 may have resulted in loss of binding sites for a repressor, possibly due to biased gene conversion.[8][9]
^ abPollard KS, Salama SR, Lambert N, Lambot MA, Coppens S, Pedersen JS, Katzman S, King B, Onodera C, Siepel A, Kern AD, Dehay C, Igel H, Ares M Jr, Vanderhaeghen P, Haussler D (2006-08-16). "An RNA gene expressed during cortical development evolved rapidly in humans" (PDF). Nature. 443 (7108): 167–172. Bibcode:2006Natur.443..167P. doi:10.1038/nature05113. PMID 16915236. S2CID 18107797. supplement
^ abcPollard KS, Salama SR, King B, Kern AD, Dreszer T, Katzman S, Siepel A, Pedersen JS, Bejerano G, Baertsch R, Rosenbloom KR, Kent J, Haussler D (October 2006). "Forces shaping the fastest evolving regions in the human genome". PLoS Genet.2 (10): e168. doi:10.1371/journal.pgen.0020168. PMC 1599772. PMID 17040131.
^Kostka D, Hubisz MJ, Siepel A, Pollard KS (March 2012). "The role of GC-biased gene conversion in shaping the fastest evolving regions of the human genome". Mol. Biol. Evol.29 (3): 1047–57. doi:10.1093/molbev/msr279. PMC 3278478. PMID 22075116.
^Pollard, Katherine (2009). "What Makes Us Human?". Scientific American. 300 (5): 44–49. Bibcode:2009SciAm.300e..44P. doi:10.1038/scientificamerican0509-44. PMID 19438048.
^Scientists Identify Gene Difference Between Humans and Chimps, Scientific American, 17 August 2006
^Researchers Identify Human DNA on the Fast Track, Howard Hughes Medical Institute website, 16 August 2006.
^"HACNS1: Gene enhancer in evolution of human opposable thumb". Science Codex. September 4, 2008. Retrieved May 17, 2010.
^"Loss-of-Function Mutation in a Repressor Module of Human-Specifically Activated Enhancer HACNS1". Molecular Biology and Evolution. September 22, 2011. Archived from the original on April 15, 2013.
^Zimov, S. (February 6, 2009). "Comment on "Human-Specific Gain of Function in a Developmental Enhancer"". Science. 323 (5915): 714–5, author reply 714-5. doi:10.1126/science.323.5915.714a. PMID 19197041. S2CID 31587069.
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