Epistasis: Its role in complex traits and speciation

描述（由申请人提供）：我们的目标是利用理论模型、数量遗传学、分子遗传学和面粉甲虫（Tribolium属）的实验群体的结合，更好地理解基因相互作用（上位性）在产生复杂表型中的作用。我们的具体目标是分离、绘制和比较在(1)种群间杂交中导致交配成功率、生存能力和生育能力降低的基因与在(2)种间杂交中导致适合度降低的基因。不相容基因的相互作用方式与引起人类遗传疾病、癌症易感性和病原体抗性的基因相同。首先，我们将探讨(1)男性合子前不育的遗传基础；(2) castaneum种群间杂交的合子后生殖隔离现象。我们的统计遗传学研究表明，来自中美洲、南美洲和非洲的3对群体的F2和回交中，母体效应和上位性导致生存力和生育适应性降低。然而，由于统计遗传学方法平均了不同基因组合的积极和消极影响，我们将使用Tribolium基因组的微卫星图来剖析基因相互作用的平均影响到它们的单个位点成分。由于3对部分分离的种群中的每一对都与实验室菌株具有完全的可育性，因此我们将通过与实验室菌株的反向回交来创建重组基因系，以便在两种背景中分离出这些基因，当种群间杂交结合时，会导致生殖不相容。第二。我们将在种间杂交中鉴定出castaneum中相互作用以及与T. freemani基因相互作用导致杂交雄虫畸形和杂交雄虫不育的基因。我们将比较castaneum种群间杂交中降低适合度的基因组与降低其与freemani的种间杂交适合度的基因组。我们可以确定相互作用降低castaneum种群间杂交适合度的基因是否是降低种间杂交适合度的基因的一个子集。后者必须包括物种形成后积累的一些基因差异。另外，castaneum和T. freemani之间的基因交换障碍可能代表了castaneum种群之间基因交换的早期障碍基因样本，或者它可能是独特的。

DESCRIPTION (provided by applicant): Our goal is to better understand the role of gene interactions (epistasis) in producing complex phenotypes using a combination of theoretical models, quantitative genetics, molecular genetics, and experimental populations of flour beetles, genus Tribolium. Our specific goals are to isolate, map, and compare the genes that interact to cause a reduction of mating success, viability, and fertility in (1) inter-population crosses, with those causing fitness reduction in (2) inter-specific crosses. Incompatibility genes interact in the same way as those genes causing human genetic diseases, cancer susceptibility, and pathogen resistance. First, we will investigate the genetic basis of (1) pre-zygotic male infertility; and, (2) post-zygotic reproductive isolation observed in inter-population crosses of T. castaneum. Our statistical genetic studies indicate that maternal effects and epistasis cause reduced viability and fertility fitness in F2 and backcrosses between 3 pairs of populations from collected from Central America, South America, and Africa. However, because statistical genetic methods average positive and negative effects of different gene combinations, we will use a microsatellite map of the Tribolium genome to dissect the average effects of gene interactions into their single locus components. Because each of 3 pairs of partially isolated populations is fully inter-fertile with a laboratory strain, we will create recombinant congenic lines by reciprocal backcrosses to the lab strain in order to isolate those genes in each of the two backgrounds, which, when combined-by inter-population crosses, cause reproductive incompatibility. Second. we will identify the genes in T. castaneum, which interact with one another and with genes from T. freemani, to cause hybrid male deformities and hybrid male inviability in inter-specific crosses. We will compare the sets of genes reducing fitness in inter-population crosses in T. castaneum with those diminishing the fitness of its inter-specific hybrids with T. freemani. We can determine whether the genes interacting to reduce the fitness of T. castaneum inter-population crosses are a subset of those reducing hybrid fitness in inter-specific crosses. The latter must include some gene differences accumulated after speciation. Alternatively, the barrier to gene exchange between T. castaneum and T. freemani may represent either, a sample of the genes posing incipient barriers, to gene exchange between populations of T. castaneum, or it may be unique.