Evolution of individually distinctive major urinary protein profiles in the house

家中个体独特的主要尿蛋白谱的演变

基本信息

批准号：
8512582
负责人：
Michael J Sheehan
金额：
$ 4.92万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8512582
关键词：
Address Advertising Allergens Animal Model Area Asthma Behavioral Behavioral Assay Biological Assay Biology Case Study Chromosomes, Human, Pair 4 Collaborations Comparative Study Copy Number Polymorphism DNA DNA Sequence Data Equilibrium Evolution Family Female Frequencies Gene Dosage Gene Expression Gene Expression Profile Genes Genetic Genetic Identity Genetic Models Genetic Polymorphism Genetic Variation Genomics Genotype Goals Health House mice Housing Human Inbreeding Individual Laboratories Letters Link Mass Spectrum Analysis Mediating Methods Modality Modeling Molecular Molecular Evolution Mus Mus musculus domesticus Nature Pattern Phenotype Population Population Genetics Prevalence Process Proteins Public Health Regulation Relative (related person)Research Risk Role Sensory Series Shapes Signal Transduction Social Interaction Testing Transcript Universities Urine Variant Work base insight interest major urinary proteins male mouse Mup1 protein next generation sequencing protein profiling social tool trait

项目摘要

DESCRIPTION (provided by applicant): Recognizing individual social partners requires that they have variable, individually distinctive phenotypes. Despite the importance of recognition in mediating social interactions, relatively few studies have examined how the extreme phenotypic variation used for recognition evolves. Theoretical work suggests that variation in identity signaling traits is maintained by negative frequency-dependent selection, though no studies have directly examined the underlying genetics of identity signals to test this hypothesis. Here we propose to use the house mouse, Mus musculus domesticus, the premier mammalian model organism, to study the genetic basis of extreme variation in identity signaling phenotypes. Scent-based individual recognition in mice is mediated by distinctive major urinary protein (MUP) profiles in urine. MUPs are the products of a family of tandemly duplicated Mup genes on chromosome 4. Using the F1 male progeny of wild-caught mice, our study will examine the variation in MUP profiles in three ways. (1). Our first objective is to document patterns of DNA sequence variation at Mup loci in natural populations. Comparisons of inbred laboratory strains and our preliminary analyses suggest that distinctive MUP profiles result from a combination of allelic and gene copy number polymorphism. We will use patterns of DNA sequence variation to test for evidence of negative frequency-dependent selection maintaining MUP diversity. (2). We will examine patterns of Mup gene expression in wild-derived mouse progeny. Previous studies have indicated that Mup loci are variably expressed across inbred laboratory strains. We will document patterns of Mup expression within and between individuals. Different patterns of expression for the same Mup gene across individuals would suggest that lineage-specific differences in Mup regulation may be an important contributor to the highly variable phenotypes found in natural populations. (3). The relative importance of allelic, gene copy number and regulatory variation in producing distinctive phenotypes is unknown. We will determine the relative contributions of each form of genetic variation to distinctiveness by comparing urine profiles with genetic data for the same individuals. Additionally, we will test if protein variatio is recognizable as individually distinct by females, linking genes to proteins to behavioral phenotypes. This work will be done in collaboration with Drs Robert Beynon and Jane Hurst (University of Liverpool, UK), two recognized experts in these areas respectively.

描述（由申请人提供）：识别个体社会伙伴需要他们具有可变的、个体独特的表型。尽管识别在调节社会互动中很重要，但相对较少的研究探讨了用于识别的极端表型变异是如何进化的。理论工作表明，身份信号特征的变异是通过负频率依赖选择来维持的，尽管没有研究直接检查身份信号的潜在遗传学来检验这一假设。在这里，我们建议使用家鼠，即首要的哺乳动物模式生物，来研究身份信号表型极端变异的遗传基础。小鼠基于气味的个体识别是由尿液中独特的主要尿蛋白（MUP）特征介导的。 MUP 是 4 号染色体上一系列串联复制的 Mup 基因家族的产物。我们的研究将使用野生捕获小鼠的 F1 雄性后代，以三种方式检查 MUP 谱的变异。 (1). 我们的第一个目标是记录自然群体中 Mup 位点的 DNA 序列变异模式。近交实验室菌株的比较和我们的初步分析表明，独特的 MUP 谱是等位基因和基因拷贝数多态性组合的结果。我们将使用 DNA 序列变异模式来测试维持 MUP 多样性的负频率依赖选择的证据。（2）。我们将检查野生小鼠后代中 Mup 基因的表达模式。先前的研究表明，Mup 基因座在近交实验室菌株中的表达存在差异。我们将记录个体内部和个体之间的 Mup 表达模式。同一 Mup 基因在个体之间的不同表达模式表明，Mup 调节的谱系特异性差异可能是自然群体中发现的高度可变表型的重要贡献者。（3）。等位基因、基因拷贝数和调控变异在产生独特表型方面的相对重要性尚不清楚。我们将通过将尿液特征与同一个体的遗传数据进行比较，确定每种形式的遗传变异对独特性的相对贡献。此外，我们将测试女性是否可以将蛋白质变异识别为个体独特，从而将基因、蛋白质与行为表型联系起来。这项工作将与罗伯特·贝农 (Robert Beynon) 博士和简·赫斯特 (Jane Hurst) 博士（英国利物浦大学）合作完成，他们分别是这些领域的两位公认专家。