ArticleMolecular biology and evolution2013
Reproduction and immunity-driven natural selection in the human WFDC locus.
Article in Molecular biology and evolution, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- Large-scale CRISPR/Cas9 deletions within the WFDC gene cluster uncover gene functionality and critical roles in mammalian reproduction.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Versatile whey acidic protein four-disulfide core domain proteins: biology and role in diseases.Frontiers in cell and developmental biology · 2024Review
- Using controls to limit false discovery in the era of big data.BMC bioinformatics · 2018Article
- An efficient algorithm for generating the internal branches of a Kingman coalescent.Theoretical population biology · 2018Article
- Whole exome sequencing in three families segregating a pediatric case of sarcoidosis.BMC medical genomics · 2018Article
- Article
- Proteomic analysis of egg white heparin-binding proteins: towards the identification of natural antibacterial molecules.Scientific reports · 2016Article
- Non-hormonal male contraception: A review and development of an Eppin based contraceptive.Pharmacology & therapeutics · 2016Review
- Analysis of intestinal microbiota in hybrid house mice reveals evolutionary divergence in a vertebrate hologenome.Nature communications · 2015Article
- Interacting proteins on human spermatozoa: adaptive evolution of the binding of semenogelin I to EPPIN.PloS one · 2013Article
- Sequence diversity of Pan troglodytes subspecies and the impact of WFDC6 selective constraints in reproductive immunity.Genome biology and evolution · 2013Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 4 countries.
Funding
Abstract
The whey acidic protein (WAP) four-disulfide core domain (WFDC) locus located on human chromosome 20q13 spans 19 genes with WAP and/or Kunitz domains. These genes participate in antimicrobial, immune, and tissue homoeostasis activities. Neighboring SEMG genes encode seminal proteins Semenogelin 1 and 2 (SEMG1 and SEMG2). WFDC and SEMG genes have a strikingly high rate of amino acid replacement (dN/dS), indicative of responses to adaptive pressures during vertebrate evolution. To better understand the selection pressures acting on WFDC genes in human populations, we resequenced 18 genes and 54 noncoding segments in 71 European (CEU), African (YRI), and Asian (CHB + JPT) individuals. Overall, we identified 484 single-nucleotide polymorphisms (SNPs), including 65 coding variants (of which 49 are nonsynonymous differences). Using classic neutrality tests, we confirmed the signature of short-term balancing selection on WFDC8 in Europeans and a signature of positive selection spanning genes PI3, SEMG1, SEMG2, and SLPI. Associated with the latter signal, we identified an unusually homogeneous-derived 100-kb haplotype with a frequency of 88% in Asian populations. A putative candidate variant targeted by selection is Thr56Ser in SEMG1, which may alter the proteolytic profile of SEMG1 and antimicrobial activities of semen. All the well-characterized genes residing in the WDFC locus encode proteins that appear to have a role in immunity and/or fertility, two processes that are often associated with adaptive evolution. This study provides further evidence that the WFDC and SEMG loci have been under strong adaptive pressure within the short timescale of modern humans.
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