signature=98a66630de90f9767b64c981fe00d1c1,Differing Evolutionary Histories of WFDC8 (Short-Term Bal...

摘要：

The four-core (WFDC) gene cluster on 20q13, harbors 15 small genes with roles in innate immunity, , and regulation of endogenous kallikreins. The WFDC cluster has emerged as a prime example of rapid diversification and adaptive evolution in . This study sought a better understanding of the evolutionary history of WFDC genes in and focused on exploring the adaptive selection signatures found in populations of European (Utah residents with ancestry from northern and western Europe [CEU]) and African (Yoruba from Ibadan, in Nigeria [YRI]) ancestry in a genome-wide scan for putative targets of recent adaptive selection. Our approach included resequencing coding and noncoding regions of , EPPIN, and in 20 CEU and of SPINT4 in 20 YRI individuals. We generated 302 kb and 60 kb of high-quality sequence data from CEU and of YRI populations, respectively, enabling the identification of 72 single nucleotide polymorphisms. Using classic neutrality tests, empirical and haplotype-based analysis, we pinpointed and SPINT4 as the likely targets of short-term balancing selection in the CEU population, and recent positive selection (incomplete selective sweep) in the YRI population. Putative candidate variants targeted by selection include 44A (rs7273669A) for , which may downregulate gene expression by abolishing the site of two factors; and a haplotype configuration [Ser73+98A] (rs6017667A-rs6032474A) for SPINT4, which may simultaneously affect protein function and gene regulation. We propose that the evolution of and SPINT4 has been shaped by complex selective scenarios due to the interdependence of variant fitness and ecological variables.

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