Genetic basis of sperm competition in Peromyscus

描述(申请人提供)：调控实验室小鼠繁殖成功的基因为哺乳动物生殖的分子和发育过程提供了重要的见解，并作为研究人类不孕不育的模型。然而，传统品系的实验室小鼠并没有表现出人们在自然界中看到的生殖特征的变异程度。相比之下，与实验室小鼠关系密切的Permyscus属小鼠，在不同物种之间的睾丸大小、射精特征、精子形态和游泳能力方面表现出显著的差异。这种变异可能是由于属内交配系统的极端分化所致。在雌性在一个繁殖季节多次交配的物种中，不同雄性的精液之间存在着激烈的竞争，以求使其卵子受精。因此，在杂交种的竞争下，提高受精成功率的雄性生殖性状存在很大的选择压力。这项拟议的研究旨在利用男性生殖特征的这种自然变异来揭示有助于受精成功的基因，并利用老鼠身上可用的丰富基因组学工具。这项研究将关注的两个姐妹物种，黑线姬鼠(异居)和小儿麻痹症(一夫一妻制)是相互干扰的，这使得人们能够测量物种内和物种之间精子竞争的强度。使用实验室配对实验，其中男性或女性与多个伴侣配对，我将测量男性生殖成功的变异，以检验关于观察到的表型差异的适应性意义的假设。然后，我将使用一种结合匿名标记和候选基因的遗传图谱方法来识别遗传区域，并最终识别有助于男性受精成功的基因。这一实验设计使我们能够直接将精子特征的表型差异与基因变异联系起来。这项研究的广泛目标是利用这一独特的系统来揭示精子竞争影响男性生殖特征的遗传基础，从而扩大我们对生殖生物学和男性不育的理解。相关性：这项研究与美国国立卫生研究院的任务直接相关，因为它将识别和分子表征影响男性生殖成功的特征。这种方法可能会在实验室小鼠身上发现不同于那些调节生育能力的基因，这些基因不会在交配系统中显示出Permyscus所做的极端差异，也不会在人类中发现不同的基因，在那里这样的对照实验是不可能的。这些基因的识别可能会为男性不育提供重要的见解，超过10%的夫妇遇到了这个问题。

DESCRIPTION (provided by applicant): Genes regulating reproductive success in laboratory mice have provided important insights into the molecular and developmental processes underlying mammalian reproduction and have served as models for studies of human infertility. Traditional strains of laboratory mice, however, do not show the degree of variation in reproductive traits that one sees in nature. In contrast, a close relative to the laboratory mouse, the genus Peromyscus, exhibit striking differences in testes size, ejaculate traits, sperm morphology and swimming performance between species. This variation is likely due to the extreme divergence in mating system within the genus. In species where females mate multiple times over a breeding season, there is intense competition between ejaculates of different males for fertilization of her eggs. Accordingly, there is strong selective pressure on male reproductive traits that improve fertilization success under competition in promiscuous species. The proposed study is designed to exploit this natural variation in male reproductive traits to reveal genes that contribute to fertilization success, and capitalizes on a wealth of genomics tools available in mice. The two sister species on which this study will focus, P. maniculatus (promiscuous) and P. polionotus (monogamous), are interfertile, allowing one to measure the intensity of sperm competition both within and between species. Using laboratory pairing experiments in which either males or females are paired with multiple partners, I will measure variation in male reproductive success to test hypotheses on the adaptive significance of the observed phenotypic differences. I will then use a genetic mapping approach that combines anonymous markers and candidate genes to identify genetic regions and ultimately genes that contribute to male fertilization success. This experimental design allows us to directly link phenotypic differences in sperm traits with genotypic variation. The broad goal of this research is to use this unique system to uncover the genetic basis of male reproductive traits influenced by sperm competition, thereby expanding our understanding of reproductive biology and male infertility. Relevance: This research is of direct relevance to the mission of NIH because it will identify and molecularly characterize traits affecting male reproductive success. This approach will likely uncover genes different from those regulating fertility in laboratory mice, which do not show the extreme divergence in mating system that Peromyscus does, or in humans, where such controlled experiments are not possible. The identification of such genes may provide important insights into male infertility, a problem encountered by over 10% of couples.