Publication Date:
2011-03-11
Description:
Humans differ from other animals in many aspects of anatomy, physiology, and behaviour; however, the genotypic basis of most human-specific traits remains unknown. Recent whole-genome comparisons have made it possible to identify genes with elevated rates of amino acid change or divergent expression in humans, and non-coding sequences with accelerated base pair changes. Regulatory alterations may be particularly likely to produce phenotypic effects while preserving viability, and are known to underlie interesting evolutionary differences in other species. Here we identify molecular events particularly likely to produce significant regulatory changes in humans: complete deletion of sequences otherwise highly conserved between chimpanzees and other mammals. We confirm 510 such deletions in humans, which fall almost exclusively in non-coding regions and are enriched near genes involved in steroid hormone signalling and neural function. One deletion removes a sensory vibrissae and penile spine enhancer from the human androgen receptor (AR) gene, a molecular change correlated with anatomical loss of androgen-dependent sensory vibrissae and penile spines in the human lineage. Another deletion removes a forebrain subventricular zone enhancer near the tumour suppressor gene growth arrest and DNA-damage-inducible, gamma (GADD45G), a loss correlated with expansion of specific brain regions in humans. Deletions of tissue-specific enhancers may thus accompany both loss and gain traits in the human lineage, and provide specific examples of the kinds of regulatory alterations and inactivation events long proposed to have an important role in human evolutionary divergence.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071156/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071156/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McLean, Cory Y -- Reno, Philip L -- Pollen, Alex A -- Bassan, Abraham I -- Capellini, Terence D -- Guenther, Catherine -- Indjeian, Vahan B -- Lim, Xinhong -- Menke, Douglas B -- Schaar, Bruce T -- Wenger, Aaron M -- Bejerano, Gill -- Kingsley, David M -- 1 F32 HD062137-01/HD/NICHD NIH HHS/ -- P50 HG002568/HG/NHGRI NIH HHS/ -- P50 HG002568-10/HG/NHGRI NIH HHS/ -- R01 HD059862/HD/NICHD NIH HHS/ -- R01 HD059862-03/HD/NICHD NIH HHS/ -- R01 HG005058/HG/NHGRI NIH HHS/ -- R01 HG005058-03/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Mar 10;471(7337):216-9. doi: 10.1038/nature09774.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Computer Science, Stanford University, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21390129" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
*Biological Evolution
;
Brain/anatomy & histology/metabolism
;
Chromosomes, Mammalian/genetics
;
Conserved Sequence/genetics
;
DNA/*genetics
;
DNA, Intergenic/genetics
;
Enhancer Elements, Genetic/genetics
;
Evolution, Molecular
;
Genes, Tumor Suppressor
;
Genome, Human/*genetics
;
*Human Characteristics
;
Humans
;
Male
;
Mice
;
Organ Specificity
;
Pan troglodytes/genetics
;
Penis/anatomy & histology/metabolism
;
Regulatory Sequences, Nucleic Acid/*genetics
;
Sequence Deletion/*genetics
;
Species Specificity
;
Transgenes/genetics
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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