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Y Chromosome Evolution

Y染色体进化

基本信息

批准号：
10330459
负责人：
KATERYNA MAKOVA
金额：
$ 41.37万
依托单位：
PENNSYLVANIA STATE UNIVERSITY, THE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-02-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10330459
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

项目摘要

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.

项目概要男性特有的 Y 染色体对于性别决定和生育能力至关重要。然而，由于其高度重复结构和单倍体，其序列仅在少数哺乳动物物种中被破译，仅包括三种猿类——人类、黑猩猩和大猩猩。由于Y染色体序列的缺失，很难获得哺乳动物基因组进化的完整图像，并且阻碍了性别研究自然种群的特定动态。在这个项目中，我们选择研究猿 Y 的进化染色体，因为它们在细胞遗传学水平上在物种之间存在巨大差异，并且因为交配和影响 Y 的选择和遗传漂变的扩散模式在猿类之间差异很大。我们的目标是通过检查 Y 染色体来破译塑造猿 Y 染色体进化的进化过程种间差异和种内多样性。在目标 1 中，我们将研究猿 Y 染色体的进化建筑学。应用我们基于最新实验和计算技术的新颖方法，我们组装了大猩猩、倭黑猩猩和婆罗洲猩猩的 Y 染色体。使用这些和公开的系统发育框架中的猿 Y 组装，我们将研究 Y 染色体结构的几个特征：序列分歧、基因内容和转座元件积累。特定血统的实例 Y染色体进化的加速或减速将被识别，其原因将是在后续目标中进行探索。在目标 2 中，我们将研究影响全局 Y 染色体的进化力量通过研究 Y 染色体多样性来构建。我们将测试观察到的多样性模式是否为从公开可用的和内部生成的重测序数据推断，与随机数据一致遗传漂变或正向或负向选择。在目标 3 和 4 中，将确定选择目标。在目标 3，我们将从短读和长读转录组组装中破译单个基因序列，构建基因系统发育，并测试作用于个体基因和个体的谱系特异性选择多拷贝基因家族的基因拷贝。目标 4 将评估作用于表达式的潜在选择 Y染色体上多拷贝扩增基因家族的水平和拷贝数。这些基因是在精子发生过程中表达，其缺失与人类男性不育有关。全面的，我们的项目将对揭示猿基因组进化的复杂性产生重要影响。猿Y 染色体组装、比对和转录本目录将成为宝贵的资源解决无数长期存在的生物学问题并设计遗传标记来追踪雄性猿类在野外的扩散。这一点至关重要，因为所有研究的猿类都濒临灭绝。技巧为该项目开发的成果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、表达水平和进化的彻底研究拷贝数将极大地有助于我们了解男性不育的原因。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Dynamic evolution of great ape Y chromosomes.

DOI：
10.1073/pnas.2001749117
发表时间：
2020-10-20
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Cechova M;Vegesna R;Tomaszkiewicz M;Harris RS;Chen D;Rangavittal S;Medvedev P;Makova KD
通讯作者：
Makova KD

Scalable multiple whole-genome alignment and locally collinear block construction with SibeliaZ.