title: Population diversity and adaptive evolution in keratinization genes: impact of environment in shaping skin phenotypes.
abstract: Several studies have demonstrated the role of climatic factors in shaping skin phenotypes, particularly pigmentation. Keratinization is another well-designed feature of human skin, which is involved in modulating transepidermal water loss (TEWL). Although this physiological process is closely linked to climate, presently it is not clear whether genetic diversity is observed in keratinization and whether this process also responds to the environmental pressure. To address this, we adopted a multipronged approach, which involved analysis of 1) copy number variations in diverse Indian and HapMap populations from varied geographical regions; 2) genetic association with geoclimatic parameters in 61 populations of dbCLINE database in a set of 549 genes from four processes namely keratinization, pigmentation, epidermal differentiation, and housekeeping functions; 3) sequence divergence in 4,316 orthologous promoters and corresponding exonic regions of human and chimpanzee with macaque as outgroup, and 4) protein sequence divergence (Ka/Ks) across nine vertebrate classes, which differ in their extent of TEWL. Our analyses demonstrate that keratinization and epidermal differentiation genes are under accelerated evolution in the human lineage, relative to pigmentation and housekeeping genes. We show that this entire pathway may have been driven by environmental selection pressure through concordant functional polymorphisms across several genes involved in skin keratinization. Remarkably, this underappreciated function of skin may be a crucial determinant of adaptation to diverse environmental pressures across world populations.
authors.affiliation: Genomics and Molecular Medicine, Council for Scientific and Industrial Research-Institute of Genomics and Integrative Biology, Delhi, India mitali@igib.res.in tn.vivek@igib.res.in.
authors.forename: Pramod
authors.initials: P
authors.lastname: Gautam
authors.affiliation: Genomics and Molecular Medicine, Council for Scientific and Industrial Research-Institute of Genomics and Integrative Biology, Delhi, India mitali@igib.res.in tn.vivek@igib.res.in.
authors.forename: Amit
authors.initials: A
authors.lastname: Chaurasia
authors.affiliation: Genomics and Molecular Medicine, Council for Scientific and Industrial Research-Institute of Genomics and Integrative Biology, Delhi, India Academy of Scientific and Innovative Research, Delhi, India.
authors.forename: Aniket
authors.initials: A
authors.lastname: Bhattacharya
authors.affiliation: Academy of Scientific and Innovative Research, Delhi, India Systems Biology Group, Council for Scientific and Industrial Research-Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Ritika
authors.initials: R
authors.lastname: Grover
authors.affiliation: Genomics and Molecular Medicine, Council for Scientific and Industrial Research-Institute of Genomics and Integrative Biology, Delhi, India Academy of Scientific and Innovative Research, Delhi, India mitali@igib.res.in tn.vivek@igib.res.in.
authors.forename: Mitali
authors.initials: M
authors.lastname: Mukerji
authors.affiliation: Academy of Scientific and Innovative Research, Delhi, India Systems Biology Group, Council for Scientific and Industrial Research-Institute of Genomics and Integrative Biology, Delhi, India mitali@igib.res.in tn.vivek@igib.res.in.
authors.forename: Vivek T
authors.initials: VT
authors.lastname: Natarajan
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics*; D000818:Animals; D005075:Biological Evolution; D002980:Climate; D056915:DNA Copy Number Variations / Q000235:genetics*; D023281:Genomics; D006801:Humans; D007633:Keratins / Q000235:genetics*; D008251:Macaca / Q000235:genetics; D002679:Pan troglodytes / Q000235:genetics; D012641:Selection, Genetic / Q000235:genetics; D012880:Skin Pigmentation / Q000235:genetics*
chemical_list: D007633:Keratins
keywords: adaptive variation; climatic factors; comparative genomics; copy-number variation; keratinization; noncoding DNA; population