Epistasis: Its role in complex traits and speciation

描述(申请人提供)：我们的目标是结合理论模型、数量遗传学、分子遗传学和粉甲虫(Tribolium)的实验种群，更好地了解基因相互作用(上位性)在产生复杂表型中的作用。我们的具体目标是分离、定位和比较在(1)种群间杂交中导致交配成功率、活力和繁殖力降低的交互作用基因，以及(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那些导致人类遗传病、癌症易感性和病原体抗药性的基因相同。首先，我们将研究(1)合子前雄性不育的遗传基础；(2)在种群间杂交中观察到的合子后生殖隔离。我们的统计遗传研究表明，母本效应和上位性导致来自中美洲、南美洲和非洲的3对群体F2和回交的存活率和育性适合度降低。然而，由于统计遗传学方法平均不同基因组合的正负效应，我们将使用Tribolium基因组的微卫星图谱将基因相互作用的平均效应分解为它们的单基因座分量。由于3对部分分离的群体中的每一对都与实验室菌株完全互交可育，我们将通过与实验室菌株的反向回交来创建重组同源基因系，以便在两个背景中的每一个中分离那些基因，当通过群体间杂交组合时，会导致生殖不亲和性。第二。我们将鉴定卡氏毛滴虫中的基因，这些基因相互作用，并与来自自由毛滴虫的基因相互作用，在种间杂交中导致杂交雄性畸形和杂交雄性丧失活力。我们将比较卡氏木霉种群间杂交中降低适合度的基因集与那些降低其种间杂交种与弗里曼锥虫适合度的基因集。我们可以确定降低种群间杂交适合度的互作基因是否是降低种间杂交中杂交适合度的基因的子集。后者必须包括物种形成后积累的一些基因差异。或者，卡氏锥虫和弗里曼锥虫之间的基因交换障碍可能是构成卡氏锥虫种群间基因交换的初始障碍的基因样本，也可能是独一无二的。

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.