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Hum Genet. 2017 Feb;136(2):193-204. doi: 10.1007/s00439-016-1748-5. Epub 2016 Nov 22.

Regional selection of the brain size regulating gene CASC5 provides new insight into human brain evolution.

Shi L1, Hu E1,2, Wang Z3, Liu J1,2, Li J4, Li M1,5, Chen H6, Yu C7, Jiang T3,8,9,10, Su B11.

Author information

1
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, People's Republic of China.
2
Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China.
3
Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
4
Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
5
Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, MD, USA.
6
Center for Computational Genomics, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
7
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, 300052, China.
8
CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
9
Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.
10
Queensland Brain Institute, University of Queensland, Brisbane, Australia.
11
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, People's Republic of China. sub@mail.kiz.ac.cn.

Abstract

Human evolution is marked by a continued enlargement of the brain. Previous studies on human brain evolution focused on identifying sequence divergences of brain size regulating genes between humans and nonhuman primates. However, the evolutionary pattern of the brain size regulating genes during recent human evolution is largely unknown. We conducted a comprehensive analysis of the brain size regulating gene CASC5 and found that in recent human evolution, CASC5 has accumulated many modern human specific amino acid changes, including two fixed changes and six polymorphic changes. Among human populations, 4 of the 6 amino acid polymorphic sites have high frequencies of derived alleles in East Asians, but are rare in Europeans and Africans. We proved that this between-population allelic divergence was caused by regional Darwinian positive selection in East Asians. Further analysis of brain image data of Han Chinese showed significant associations of the amino acid polymorphic sites with gray matter volume. Hence, CASC5 may contribute to the morphological and structural changes of the human brain during recent evolution. The observed between-population divergence of CASC5 variants was driven by natural selection that tends to favor a larger gray matter volume in East Asians.

PMID:
27878434
DOI:
10.1007/s00439-016-1748-5
[Indexed for MEDLINE]

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