title: Regional selection of the brain size regulating gene CASC5 provides new insight into human brain evolution.
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.
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, People's Republic of China.|Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Enzhi
authors.initials: E
authors.lastname: Hu
authors.affiliation: Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Zhenbo
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, People's Republic of China.|Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Jiewei
authors.initials: J
authors.lastname: Liu
authors.affiliation: Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, People's Republic of China.|Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Center for Computational Genomics, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, 300052, China.
authors.forename: Chunshui
authors.initials: C
authors.lastname: Yu
authors.affiliation: Institute of Zoology, Chinese Academy of Sciences, Beijing, China.|CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.|Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.|Queensland Brain Institute, University of Queensland, Brisbane, Australia.
authors.forename: Tianzi
authors.initials: T
authors.lastname: Jiang
authors.affiliation: 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.
authors.forename: Bing
authors.initials: B
authors.lastname: Su
mesh_terms: D000328:Adult; D000483:Alleles; D000818:Animals; D044466:Asian People / Q000235:genetics; D005075:Biological Evolution; D001921:Brain / Q000033:anatomy & histology*; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D056084:Genetic Fitness; D015894:Genome, Human; D060005:Genotyping Techniques; D066128:Gray Matter / Q000033:anatomy & histology; D006239:Haplotypes; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D015810:Linkage Disequilibrium; D008251:Macaca / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D009929:Organ Size / Q000235:genetics*; D002679:Pan troglodytes / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: C472643:Knl1 protein, human; D008869:Microtubule-Associated Proteins