title: Recent Positive Selection in Genes of the Mammalian Epidermal Differentiation Complex Locus.
abstract: The epidermal differentiation complex (EDC) is the most rapidly evolving locus in the human genome compared to that of the chimpanzee. Yet the EDC genes that are undergoing positive selection across mammals and in humans are not known. We sought to identify the positively selected genetic variants and determine the evolutionary events of the EDC using mammalian-wide and clade-specific branch- and branch-site likelihood ratio tests and a genetic algorithm (GA) branch test. Significant non-synonymous substitutions were found infilaggrin, SPRR4, LELP1, andS100A2genes across 14 mammals. By contrast, we identified recent positive selection inSPRR4in primates. Additionally, the GA branch test discovered lineage-specific evolution for distinct EDC genes occurring in each of the nodes in the 14-mammal phylogenetic tree. Multiple instances of positive selection forFLG, TCHHL1, SPRR4, LELP1, andS100A2were noted among the primate branch nodes. Branch-site likelihood ratio tests further revealed positive selection in specific sites inSPRR4, LELP1, filaggrin, andrepetinacross 14 mammals. However, in addition to continuous evolution ofSPRR4, site-specific positive selection was also found inS100A11, KPRP, SPRR1A, S100A7L2, andS100A3in primates andfilaggrin, filaggrin2, andS100A8in great apes. Very recent human positive selection was identified in thefilaggrin2L41 site that was present in Neanderthal. Together, our results identifying recent positive selection in distinct EDC genes reveal an underappreciated evolution of epidermal skin barrier function in primates and humans.
authors.affiliation: Division of Dermatology, Department of Internal Medicine, Center for Pharmacogenomics and Center for the Study of Itch, Washington University School of Medicine, St. Louis MO, USA.
authors.forename: Zane A
authors.initials: ZA
authors.lastname: Goodwin
authors.affiliation: Division of Dermatology, Department of Internal Medicine, Center for Pharmacogenomics and Center for the Study of Itch, Washington University School of Medicine, St. Louis MO, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: de Guzman Strong
keywords: barrier; epidermal differentiation complex; epidermis; evolution; positive selection; skin