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：
7797653
负责人：
Heidi S Fisher
金额：
$ 5.38万
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生殖的分子和发育过程提供了重要的见解，并已成为人类不育研究的模型。然而，传统的实验室小鼠品系并没有表现出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白鼠属（Peromyscus）在不同物种之间的睾丸大小、射精特征、精子形态和游泳性能方面表现出显着差异。这种变异可能是由于该属内交配系统的极端分歧造成的。在雌性在繁殖季节多次交配的物种中，不同雄性的射精之间会为了卵子的受精而进行激烈的竞争。因此，对雄性生殖性状存在强大的选择压力，这些性状在杂乱物种的竞争下提高受精成功率。拟议的研究旨在利用雄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，并利用小鼠中可用的大量基因组学工具。本研究将重点关注的两个姐妹物种，P. maniculatus（混交）和 P. poliionotus（一夫一妻制），是不育的，因此可以测量物种内部和物种之间精子竞争的强度。通过实验室配对实验，其中雄性或雌性与多个伴侣配对，我将测量雄性繁殖成功率的变化，以检验关于观察到的表型差异的适应性意义的假设。然后，我将使用遗传作图方法，结合匿名标记和候选基因来识别遗传区域，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直接联系起来。这项研究的总体目标是利用这一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，从而扩大我们对生殖生物学和男性不育症的理解。相关性：这项研究与 NIH 的使命直接相关，因为它将识别影响男性生殖成功的特征并进行分子表征。这种方法可能会发现与实验室小鼠中调节生育力的基因不同的基因，这些基因没有显示出白鼠属的交配系统的极端差异，或者在人类中，这样的对照实验是不可能的。这些基因的鉴定可能为男性不育症提供重要的见解，这是超过 10% 的夫妇遇到的问题。