Evolutionary genetics of speciation

我的研究是在努力了解物种形成的遗传基础的前沿。我和我的学生研究基因的群体遗传学，这些基因编码的蛋白质介导了同一物种成员之间的生殖相容性和不同物种之间的生殖隔离。这项研究的重点是海星的简单配偶选择，基于精子和卵子表面表达的少量基因。理论和实验表明，男性之间的精子竞争和男性和女性之间的性冲突与受精相关的风险可能会导致种群进化出不同的男性和女性特征组合，如精子和卵蛋白，导致配子相容性，生殖隔离和物种形成的种群差异。短期的研究目标是测试这些预测的多配子识别基因系统和多个海星星物种，并与配子识别基因的选择模式的功能，这些基因产物在精卵相容性受精。这项研究的长期目标是在分子水平上了解选择如何导致物种形成。 这项拟议的研究建立在我们最近在以下方面取得的成功之上： (1)查明几个海星星星物种中的老种群隔离情况（在那里最容易发现早期的物种形成阶段）; (2)证明了一种加拿大物种（蝙蝠星星，Patiria miniata）的种群之间的进化差异是由精子顶体蛋白结合蛋白和卵壳结合蛋白受体OBi 1的氨基酸差异选择引起的; (3)为精子和卵子中表达的许多受精基因的新的高通量下一代测序开发专业知识和基础设施。 我们的新研究将这项工作扩展到在受精过程中不同时间起作用的基因;物种形成过程中不同阶段的种群;以及具有不同交配系统特征（和性冲突强度）的物种。高通量转录组学的使用是一项关键创新，使我们能够克服使用传统PCR和测序方法的先前工作的重大限制。 这项新研究的结果将首次在分子水平上全面了解受精基因的选择如何影响生殖隔离的进化和新物种的形成。 我们最近在海星星星种群中发现了bindin和OBi 1之间的协同进化，这引起了人们对哺乳动物受精过程中精子和卵子表达基因的可比系统的兴趣。继之前对小鼠和人类卵被中的ZP 3蛋白和精子头中的ZP 3R受体的研究之后，我们使用了来自1000个基因组计划（人类遗传变异数据库）的数据，以显示每个基因中一个位点的选择证据，导致所有人类群体共享的两个基因之间特定等位基因的非随机组合。ZP 3和ZP 3R之间的这种强连锁可能是由交配期间的选择引起的，该选择有利于具有一些雌性ZP 3基因型的卵子通过具有匹配的雄性ZP 3R基因型的精子受精。相反，ZP 3/ZP 3R错配可能是人类不育的原因之一。我建议跟进这一最近的发现，对IVF治疗中的临床人群进行研究，以检验以下假设：由于男女基因型不匹配，某些ZP 3/ZP 3R基因型组合在不育家庭中的代表性过高。

My research is at the leading edge of efforts to understand the genetic basis for speciation. My students and I study the population genetics of genes that encode proteins mediating reproductive compatibility among members of the same species and reproductive isolation between different species. The research focuses on sea stars with simple mate selection based on a small number of genes expressed on the surfaces of sperm and eggs. Theory and experiments show that sperm competition among males and sexual conflict between males and females over risks associated with fertilization can cause populations to evolve different combinations of male and female traits such as sperm and egg proteins, leading to population differences in gamete compatibility, reproductive isolation, and speciation. The short-term research objectives are to test these predictions for multiple gamete recognition gene systems and multiple sea star species, and relate the pattern of selection on gamete recognition genes to the function of those gene products in sperm-egg compatibility at fertilization. The long-term goal of the research is to understand at the molecular level how selection causes speciation. This proposed research builds on our recent success in: (1) identifying cases of old population isolation (where early stages of speciation are most easily detected) within several sea star species; (2) demonstrating evolutionary divergence between populations of one Canadian species (the bat star, Patiria miniata) caused by selection for amino acid differences in the sperm acrosomal protein bindin and the egg coat bindin receptor OBi1; and (3) developing expertise and infrastructure for new high-throughput next-generation sequencing of many fertilization genes expressed in sperm and eggs. Our new studies extend this work to genes acting at different times during fertilization; to populations at different stages in the speciation process; and to species with different mating system traits (and intensities of sexual conflict). The use of high-throughput transcriptomics is a key innovation that allows us to overcome significant limitations on previous work that used traditional PCR and sequencing methods. The results of this new research will for the first time give a comprehensive view at the molecular level of how selection on fertilization genes can shape the evolution of reproductive isolation and the formation of new species. Our recent discovery of coevolution between bindin and OBi1 in sea star populations led to interest in a comparable system of sperm- and egg-expressed genes in mammalian fertilization. Following on previous studies of the ZP3 protein in the egg coat and the ZP3R receptor in the sperm head of mice and humans, we used data from the 1000 Genomes Project (a database of human genetic variation) to show evidence for selection at one site in each gene, leading to non-random combinations of specific alleles between the two genes that are shared among all human populations. This strong linkage between ZP3 and ZP3R is probably caused by selection during mating that favours the fertilization of eggs with some female ZP3 genotypes by sperm with matching male ZP3R genotypes. Conversely, ZP3/ZP3R mismatching could be a source of human infertility. I propose to follow up this recent discovery with studies of clinical human populations in IVF treatment to test the hypothesis that some ZP3/ZP3R genotype combinations are overrepresented among infertile families due to male-female genotype mismatches.