Oral Presentation Society for Molecular Biology and Evolution Conference 2016

The case for selection at coevolving human gamete-recognition genes (ZP2, ZP3, and C4BPA) (#83)

Michael W Hart 1 , Daryn A Stover 2 , Sahar V Mozaffari 3 , Carole Ober 3 , Carina F Mugal 4 , Ingemar Kaj 4
  1. Simon Fraser University, Burnaby, British Columbia, Canada
  2. Arizona State University, Lake Havasu City, AZ, United States
  3. University of Chicago, Chicago, IL, United States
  4. Uppsala University, Uppsala, Sweden

Previous research has suggested that selection due to sexual conflict between mates over the optimal rate of sperm-egg binding has led to coevolution between male adaptations and female countermeasures at gamete recognition genes. Coevolution of pairs of gamete recognition genes expressed on sperm and eggs may be associated with both natural reproductive variation and clinical infertility in humans. We attempt to identify likely targets of selection in two genes (ZP2, ZP3) that contribute to the thick extracellular egg coat (or zona pellucida), and one gene (C4BPA) that encodes the associated sperm-head receptor. Specifically, branch-site codon models were applied to the 1000 Genomes Phase 1 dataset to identify candidate protein-coding mutations evolving under positive selection. These candidate mutations differentiated two haplogroups of intermediate frequency at each gene and may represent balanced polymorphisms. While strong linkage disequilibrium (LD) consistent with coevolving loci was not detected among candidate mutations in the 1000 Genomes dataset, significant LD was detected between ZP2 and C4BPA in a well-studied founder population of Hutterites. Candidate mutations in ZP2 and C4BPA were also significantly correlated with variation in family size and birth rate among Hutterite couples. Thus, the identified mutations may represent targets of positive selection impacting reproductive compatibility between human mates.