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

• 批准号: 8717683
• 负责人: Michael J Sheehan
• 金额: $ 4.96万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8717683
• 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 Sequence; Data; Equilibrium; Evolution; Family; Female; Frequencies; Gene Dosage; Gene Expression; Gene Expression Profile; Genes; Genetic; Genetic Identity; Genetic Models; Genetic Polymorphism; Genetic Variation; Genomic DNA; 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

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）：识别个人社会合作伙伴需要他们有可变的，个别独特的表型。尽管识别在调节社会互动中的重要性，但相对较少的研究已经研究了用于识别的极端表型变异是如何进化的。理论工作表明，身份信号特征的变化是由负频率依赖性选择维持的，尽管没有研究直接研究身份信号的潜在遗传学来验证这一假设。在这里，我们建议使用家鼠，小家鼠，总理的哺乳动物模式生物，研究身份信号表型的极端变化的遗传基础。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）谱介导的。MUP是4号染色体上串联重复的Mup基因家族的产物。使用野生捕获小鼠的F1雄性后代，我们的研究将从三个方面研究MUP谱的变化。（一）. 我们的第一个目标是记录自然人群中Mup基因座的DNA序列变异模式。比较近交系实验室菌株和我们的初步分析表明，独特的MUP配置文件的等位基因和基因拷贝数多态性的组合。我们将使用DNA序列变异的模式来测试负频率依赖性选择维持MUP多样性的证据。（二）、我们将研究Mup基因在野生小鼠后代中的表达模式。先前的研究表明，Mup基因座在近交系实验室菌株中不稳定表达。我们将记录个体内部和个体之间Mup表达的模式。不同模式的表达相同的Mup基因在不同的个人表明，特定的谱系差异Mup调节可能是一个重要的贡献者在自然人群中发现的高度可变的表型。（三）、等位基因、基因拷贝数和调控变异在产生独特表型中的相对重要性尚不清楚。我们将通过比较同一个体的尿液特征和遗传数据来确定每种形式的遗传变异对独特性的相对贡献。此外，我们将测试蛋白质变异是否可被女性识别为个体差异，将基因与蛋白质与行为表型联系起来。这项工作将与罗伯特·贝农博士和简·赫斯特博士（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。