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: 8315623
• 负责人: Michael J Sheehan
• 金额: $ 4.71万
• 依托单位: UNIVERSITY OF ARIZONA
• 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 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8315623
• 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; 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. PUBLIC HEALTH RELEVANCE: House mice are a superb mammalian model for addressing basic questions in genetics of relevance to human health, including such things as the forces maintaining genetic variation in natural populations, the extent and dynamics of copy-number variation, and variation in gene expression patterns. In addition to providing insight on the nature of sequence, copy number and expression variation underlying a socially important phenotype, mouse major urinary proteins (MUPs) are also of public health interest because they are common allergens and their prevalence is linked to asthma risk (Phipatanakul et al. 2000; Cohn et al. 2004).

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。尽管识别在调解社会互动中很重要，但相对较少的研究调查了用于识别的极端表型变异是如何演变的。理论工作表明，身份信号特征的变化是由负频率依赖选择维持的，尽管没有研究直接检查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，家鼠，主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）谱介导的。MUPs是4号染色体上一系列串联复制的Mup基因的产物。使用野生捕获小鼠的F1雄性后代，我们的研究将通过三种方式检查MUP谱的变化。（1）. 我们的第一个目标是记录自然种群中Mup位点的DNA序列变异模式。与实验室自交系的比较和我们的初步分析表明，不同的MUP谱是等位基因和基因拷贝数多态性的结合。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基因座在自交系实验室菌株中表达是可变的。我们将记录个体内部和个体之间Mup表达的模式。同一Mup基因在个体之间的不同表达模式表明，Mup调控的谱系特异性差异可能是自然种群中发现的高度可变表型的重要因素。（3）. 等位基因、基因拷贝数和调控变异在产生不同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谱和基因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被女性识别为个体不同，将基因与蛋白质与行为表型联系起来。这项工作将与Robert Beynon博士和Jane Hurst博士（英国利物浦大学）合作完成，这两位博士分别是这些领域的公认专家。