Genomics and Molecular Medicine, Council for Scientific and Industrial Research-Institute of Genomics and Integrative Biology, Delhi, India
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.
Mol Biol Evol. 2015 Mar;32(3):555-73. doi: 10.1093/molbev/msu342. Epub 2014 Dec 21.
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.
已有多项研究表明气候因素在塑造皮肤表型（尤其是肤色）方面的作用。角质化是人类皮肤的另一个精心设计的特征，它参与调节经表皮水分流失（TEWL）。尽管这个生理过程与气候密切相关，但目前尚不清楚角质化是否存在遗传多样性，以及这一过程是否也对环境压力有反应。为了解决这个问题，我们采用了一种多管齐下的方法，包括分析 1）来自不同地理区域的多种印度和 HapMap 人群中的拷贝数变异；2）在 dbCLINE 数据库的 61 个人群中，将与地理气候参数的遗传关联与 4 个过程（即角质化、色素沉着、表皮分化和管家功能）中的 549 个基因相关联；3）在人类和黑猩猩的 4,316 个同源启动子和相应外显子区域中进行序列分歧分析，以外群猕猴为代表，以及 4）在九个脊椎动物类群中进行蛋白质序列分歧（Ka/Ks）分析，这些类群在 TEWL 程度上存在差异。我们的分析表明，与色素沉着和管家基因相比，角质化和表皮分化基因在人类谱系中处于加速进化的状态。我们表明，整个途径可能是由于环境选择压力，通过涉及皮肤角质化的几个基因的功能协同多态性驱动的。值得注意的是，皮肤的这种未被充分认识的功能可能是世界人口适应各种环境压力的关键决定因素。
