Genetic basis of sperm competition in Peromyscus

白鼠精子竞争的遗传基础

基本信息

批准号：
7591739
负责人：
Heidi S Fisher
金额：
$ 5.17万
依托单位：
HARVARD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-04-01 至 2011-05-31
项目状态：
已结题

项目摘要

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.

描述（由申请人提供）：调节实验室小鼠生殖成功的基因为哺乳动物繁殖的分子和发育过程提供了重要的见解，并已成为研究人类不育症的模型。但是，实验室小鼠的传统菌株并未显示出在自然界中看到的生殖特征的变化程度。相比之下，相对于实验室小鼠的亲密关系，peromyscus属在睾丸大小，射精特征，精子形态和物种之间的游泳表现上表现出明显的差异。这种变化可能是由于该属内交配系统的极端差异所致。在雌性在一个繁殖季节多次交配的物种中，不同雄性的射精之间存在激烈的竞争，以供卵子受精。因此，在滥交物种的竞争下，在男性生殖特征上有强烈的选择压力，可以改善受精成功。拟议的研究旨在利用男性生殖特征的这种自然变异，以揭示有助于受精成功的基因，并利用小鼠可用的大量基因组学工具。 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.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化，以测试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映射方法来鉴定遗传区域和最终导致男性施肥成功的基因。这种实验设计使我们能够将精子性状的表型差异与基因型变异联系起来。这项研究的广泛目的是利用这种独特的系统来揭示受精子竞争影响的男性生殖特征的遗传基础，从而扩展了我们对生殖生物学和男性不育的理解。相关性：这项研究与NIH的使命是直接相关的，因为它将确定并分子表征影响男性生殖成功的特征。这种方法可能会发现与调节实验室小鼠生育能力的基因不同，而实验室小鼠中没有表现出Peromyscus所做的交配系统中的极端差异，或者在人类中无法进行这种受控的实验。这种基因的鉴定可能会为男性不育症提供重要的见解，这是超过10％的夫妻遇到的问题。