Evolutionary genetics of speciation

我的研究处于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调节同一物种成员之间的生殖亲和力，以及不同物种之间的生殖隔离。这项研究的重点是海星，根据精子和卵子表面表达的少量基因进行简单的交配选择。理论和实验表明，雄性之间的精子竞争以及雄性和雌性之间关于受精相关风险的性别冲突可以导致种群进化出不同的雄性和雌性特征的组合，如精子和卵蛋白，从而导致种群在配子兼容性、生殖隔离和物种形成方面的差异。短期的研究目标是检验这些对多配子识别基因系统和多个海星物种的预测，并将配子识别基因的选择模式与这些基因产物在受精时精卵相容中的功能联系起来。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的基础上： (1)确定几个海星物种中的旧种群隔离情况(最容易发现物种形成的早期阶段)； (2)通过选择精子顶体蛋白结合蛋白和卵衣结合蛋白受体OBi1中的氨基酸差异，显示了加拿大一个物种(蝙蝠星，Patiria mini ata)种群之间的进化差异；以及 (3)为在精子和卵子中表达的许多受精基因进行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(和性别冲突强度)的物种。高通量转录组的使用是一项关键的创新，它使我们克服了以前使用传统的聚合酶链式反应和测序方法的工作的重大限制。 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塑造生殖隔离的进化和新物种的形成。 我们最近在海星种群中发现了Bindin和Obi1之间的共同进化，这引发了人们对哺乳动物受精中精子和卵子表达基因的类似系统的兴趣。在之前对小鼠和人类卵壳中的ZP3蛋白和精子头中的ZP3R受体的研究之后，我们使用1000基因组计划(人类遗传变异数据库)的数据来证明在每个基因的一个位置进行选择的证据，导致了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。ZP3和ZP3R之间的这种强连锁可能是由于交配过程中的选择所致，这种选择有利于某些雌性ZP3基因的卵子与匹配的雄性ZP3R基因的精子受精。相反，ZP3/ZP3R不匹配可能是人类不孕不育的一个来源。我建议通过对体外受精治疗中的临床人群的研究来跟进这一最近的发现，以检验这样一个假设，即由于男性和女性的基因错配，一些ZP3/ZP3R基因组合在不育家庭中的比例过高。

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.