Y Chromosome Evolution

Y染色体进化

• 批准号: 10092198
• 负责人: KATERYNA MAKOVA
• 金额: $ 41.39万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10092198
• 关键词: Address; Affect; Architecture; Biological; Catalogs; Chickens; Chromosomes; Code; Complement; Computational Technique; Computing Methodologies; Cytogenetics; DNA Resequencing; DNA Transposable Elements; Data; Disease; Evolution; Female; Fertility; Gene Dosage; Gene Family; Genes; Genetic Drift; Genetic Markers; Genome; Genomics; Goals; Gorilla gorilla; Haploidy; Human; Individual; Investigation; Male Infertility; Methods; Modeling; Multigene Family; Nature; Pan Genus; Pan paniscus; Partner in relationship; Pattern; Phylogenetic Analysis; Phylogeny; Pongidae; Pongo pygmaeus; Population; Population Sizes; Process; Proteins; Publishing; Research; Research Personnel; Resources; Sex Chromosomes; Shapes; Spermatogenesis; Structure; System; Techniques; Testing; Testis; Theoretical model; Transcript; Y Chromosome; Y protein; autosome; base; design; digital; diverse data; human male; interest; male; male fertility; mammalian genome; novel; prototype; rapid technique; sex; sex determination; simulation; sperm cell; trait; transcriptome

PROJECT SUMMARY The male-specific Y chromosome is critical for sex determination and fertility. Yet, because of its highly repetitive structure and haploidy, its sequence has only been deciphered for a handful of mammalian species, including just three apes ‒ human, chimpanzee, and gorilla. The lack of Y chromosome sequences has made it difficult to obtain a complete picture of mammalian genome evolution, and has hampered studies of sex- specific dynamics in natural populations. In this project, we have chosen to study evolution of ape Y chromosomes because they differ enormously among species at the cytogenetic level, and because mating and dispersal patterns, which influence selection and genetic drift acting on the Y, vary dramatically among apes. Our goal is to decipher the evolutionary processes shaping ape Y chromosome evolution by examining Y interspecific divergence and intraspecific diversity. In Aim 1 we will study evolution of ape Y chromosome architecture. Applying our novel method based on the latest experimental and computational techniques, we assembled the Y chromosomes of gorilla, bonobo, and Bornean orangutan. Using these and publicly available ape Y assemblies in a phylogenetic framework, we will study several features of Y chromosome architecture: sequence divergence, gene content, and transposable element accumulation. Instances of lineage-specific accelerated or decelerated evolution of Y chromosome evolution will be identified and their causes will be explored in subsequent aims. In Aim 2 we will investigate evolutionary forces affecting global Y chromosome architecture by studying Y chromosome diversity. We will test whether the observed diversity patterns, as inferred from publicly available and in-house generated re-sequencing data, are consistent with random genetic drift or with positive or negative selection. In Aims 3 and 4, the selection targets will be identified. In Aim 3, we will decipher the individual gene sequences from short- and long-read transcriptome assemblies, construct gene phylogenies, and test for lineage-specific selection acting on individual genes and on individual gene copies for multi-copy gene families. Aim 4 will evaluate potential selection acting on the expression levels and copy number of multi-copy ampliconic gene families on the Y chromosome. These genes are expressed during spermatogenesis and their deletions have been implicated in human male infertility. Overall, our project will have important implications for uncovering the intricacies of ape genome evolution. The ape Y chromosome assemblies, alignments, and transcript catalogues will serve as an invaluable resource for addressing a myriad of long-standing biological questions and for designing genetic markers to trace the dispersal of male apes in the wild. This is critical, as all studied ape species are endangered. The techniques developed for this project will be shared with other researchers, enabling them to study Y chromosomes of other species. Our thorough investigation of evolution of ampliconic gene sequence, expression levels, and copy number will significantly contribute to our understanding of the causes of male infertility.

项目摘要 男性特异性的Y染色体对于性别确定和生育至关重要。但是，由于它的高度 重复的结构和单倍体，其序列仅是为少数哺乳动物物种而决定的， 仅包括三只猿 - 人，黑猩猩和大猩猩。缺乏Y染色体序列已使它成为现实 很难获得哺乳动物基因组进化的完整图片，并且已经阻碍了性别的研究 自然种群中的特定动态。在这个项目中，我们选择研究猿的演变 染色体是因为它们在细胞遗传学水平的物种之间急剧不同，并且因为交配和交配和 在猿类之间影响选择和作用于Y的遗传漂移的分散模式在Y中有很大变化。 我们的目标是通过检查y来破译塑造猿染色体进化的进化过程 种间差异和种内多样性。在AIM 1中，我们将研究APE Y染色体的进化 建筑学。根据最新的实验和计算技术应用我们的新方法，我们 聚集了大猩猩，bonobo和Bornean Orangutan的Y染色体。使用这些并公开可用 在系统发育框架中，我们将研究Y染色体体系结构的几个特征： 序列差异，基因含量和转座元件积累。谱系特定的实例 将确定Y染色体演化的加速或减速进化，其原因将为 在随后的目标中探索。在AIM 2中，我们将研究影响全球Y染色体的进化力 通过研究Y染色体多样性来建筑。我们将测试观察到的多样性模式是否为 根据公开可用和内部生成的重新序列数据推断出来，与随机 遗传漂移或阳性或负选择。在目标3和4中，将确定选择目标。在 AIM 3，我们将从短读和长读的转录组组件中解释单个基因序列， 构建基因系统发育，并测试作用于单个基因的谱系特异性选择 多拷贝基因家族的基因拷贝。 AIM 4将评估作用于表达的潜在选择 Y染色体上的多拷贝扩增基因家族的水平和拷贝数。这些基因是 在人类不孕症中暗示了在精子发生期间表达的。全面的， 我们的项目将对揭示猿基因组进化的复杂性具有重要意义。猿 染色体组件，对齐和成绩单目录将成为宝贵的资源 解决无数长期的生物学问题，并设计遗传标记以追踪 在野外散布雄猿。这是至关重要的，因为所有Studiod Ape物种均受到威胁。技术 为该项目开发的将与其他研究人员共享，使他们能够研究Y染色体 其他物种。我们对扩增基因序列，表达水平和 拷贝数将极大地有助于我们理解男性不育症的原因。