ArticleBMC biology2013
Functional divergence of the brain-size regulating gene MCPH1 during primate evolution and the origin of humans.
Article in BMC biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 36 citations in OpenAlex.
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- Studying human and nonhuman primate evolutionary biology with powerful in vitro and in vivo functional genomics tools.Evolutionary anthropology · 2020Review
- Dissecting the Genetic and Etiological Causes of Primary Microcephaly.Frontiers in neurology · 2020Review
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- A transgenic monkey model for the study of human brain evolution.Zoological research · 2019Article
- Transgenic rhesus monkeys carrying the humanNational science review · 2019Article
- The emerging roles for the chromatin structure regulators CTCF and cohesin in neurodevelopment and behavior.Cellular and molecular life sciences : CMLS · 2018Review
- Natural Selection in the Great Apes.Molecular biology and evolution · 2016Article
- TALEN-based generation of a cynomolgus monkey disease model for human microcephaly.Cell research · 2016Article
- MCPH1: a window into brain development and evolution.Frontiers in cellular neuroscience · 2015Review
- Microcephaly genes evolved adaptively throughout the evolution of eutherian mammals.BMC evolutionary biology · 2014Article
- Primary microcephaly gene MCPH1 shows a novel molecular biomarker of human renal carcinoma and is regulated by miR-27a.International journal of clinical and experimental pathology · 2014Article
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5 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundOne of the key genes that regulate human brain size, MCPH1 has evolved under strong Darwinian positive selection during the evolution of primates. During this evolution, the divergence of MCPH1 protein sequences among primates may have caused functional changes that contribute to brain enlargement.
resultsTo test this hypothesis, we used co-immunoprecipitation and reporter gene assays to examine the activating and repressing effects of MCPH1 on a set of its down-stream genes and then compared the functional outcomes of a series of mutant MCPH1 proteins that carry mutations at the human- and great-ape-specific sites. The results demonstrate that the regulatory effects of human MCPH1 and rhesus macaque MCPH1 are different in three of eight down-stream genes tested (p73, cyclinE1 and p14ARF), suggesting a functional divergence of MCPH1 between human and non-human primates. Further analyses of the mutant MCPH1 proteins indicated that most of the human-specific mutations could change the regulatory effects on the down-stream genes. A similar result was also observed for one of the four great-ape-specific mutations.
conclusionsCollectively, we propose that during primate evolution in general and human evolution in particular, the divergence of MCPH1 protein sequences under Darwinian positive selection led to functional modifications, providing a possible molecular mechanism of how MCPH1 contributed to brain enlargement during primate evolution and human origin.
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