Genomic mechanisms of asexual reproduction

无性繁殖的基因组机制

基本信息

批准号：
10456881
负责人：
KRISTIN C GUNSALUS
金额：
$ 19.81万
依托单位：
NEW YORK UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10456881
关键词：
ATAC-seq Address Aging Alleles Animal Model Animals Architecture Asexual Reproduction Back Biochemical Biological Biology Caenorhabditis elegans Cell Aging Cell division Cells Chromatin Chromatin Conformation Capture and Sequencing Chromosome Pairing Chromosomes Cloning Code Complement DNA DNA Repair DNA Sequence Alteration DNA Sequence Rearrangement Data Defect Development Diploidy Epigenetic Process Event Evolution Female Fertility Fertilization Gene Expression Regulation Genes Genetic Genetic Recombination Genome Genomic Instability Genomics Heterozygote Homologous Gene Human Infertility Karyotype Light Link Mammals Meiosis Meiotic Recombination Modification Molecular Molecular Genetics Mutation Nature Nematoda Nuclear Oocytes Orthologous Gene Parthenogenesis Partner in relationship Pattern Phase Phylogenetic Analysis Population Process Proteins Publishing RNA Recording of previous events Sister Site Southern Blotting Structure Technology Telomere Capping Telomere Maintenance Telomere Maintenance Gene Telomere Shortening Time Work Yeasts age related asexual asexuality base chromosome fusion comparative comparative genomics genetic manipulation genome analysis genome integrity genomic signature innovation insight male nanopore novel pressure programs purge recombinational repair reconstitution reconstruction reproductive sex success telomere tool trait transcriptome transcriptome sequencing

ATAC-seq Address Aging Alleles Animal Model Animals Architecture Asexual Reproduction Back Biochemical Biological Biology Caenorhabditis elegans Cell Aging Cell division Cells Chromatin Chromatin Conformation Capture and Sequencing Chromosome Pairing Chromosomes Cloning Code Complement DNA DNA Repair DNA Sequence Alteration DNA Sequence Rearrangement Data Defect Development Diploidy Epigenetic Process Event Evolution Female Fertility Fertilization Gene Expression Regulation Genes Genetic Genetic Recombination Genome Genomic Instability Genomics Heterozygote Homologous Gene Human Infertility Karyotype Light Link Mammals Meiosis Meiotic Recombination Modification Molecular Molecular Genetics Mutation Nature Nematoda Nuclear Oocytes Orthologous Gene Parthenogenesis Partner in relationship Pattern Phase Phylogenetic Analysis Population Process Proteins Publishing RNA Recording of previous events Sister Site Southern Blotting Structure Technology Telomere Capping Telomere Maintenance Telomere Maintenance Gene Telomere Shortening Time Work Yeasts age related asexual asexuality base chromosome fusion comparative comparative genomics genetic manipulation genome analysis genome integrity genomic signature innovation insight male nanopore novel pressure programs purge recombinational repair reconstitution reconstruction reproductive sex success telomere tool trait transcriptome transcriptome sequencing

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项目摘要

Project Summary The eukaryotic innovation of genetic diversification through sex and recombination provides significant adaptive advantages. Still, the recognition that some animals are capable of asexual reproduction dates back to at least 1740 CE, and asexuality has arisen independently multiple times across the animal kingdom. This transition is often accompanied by modified meiosis and genome organization. Since meiotic defects underlie age-related decline in human fertility, and genomic instability is a hallmark of aging cells, studying how successful asexual lineages can thrive in light of major modifications to these core cellular programs can provide new molecular insights into the mechanisms of aging and infertility. To characterize genomic signatures of asexual reproduction, we previously sequenced the genome and transcriptome of Diploscapter pachys, a nematode from an unusually persistent asexual lineage estimated to have originated 18 million years ago. This work showed that D. pachys lacks key meiotic genes and the first (reductional) meiotic division, enabling reconstitution of a diploid genome in the oocyte without fertilization. Strikingly, its nuclear genome is packaged into exactly one pair of chromosomes, which we showed derives from the full fusion of all ancestral chromosomes. However, the genome assembly still contains many gaps that limit our ability to answer key questions about D. pachys evolution: how and when genome fusions and abridged meiosis arose, how a high level of sequence diversity is maintained without genetic recombination, and which molecular changes drove the transition to asexual reproduction remain a mystery. We propose to use the power of long-read sequencing and comparative genomics to address these questions. In Aim 1, we will generate a highly contiguous, chromosome-level genome assembly for D. pachys. This will reveal the pattern of ancestral chromosome fusions, whether major genome rearrangements likely preclude meiotic crossovers, and the nature of chromosome fusion sites and telomeres. In Aim 2, we will produce chromosome-level genome assemblies of four additional parthenogens and their closest known sexual relative in the same phylogenetic clade. This will allow a comparative analyses of genome architecture and enable evolutionary reconstruction of molecular genetic changes linked to asexual reproduction. In Aim 3, we will analyze chromatin accessibility and changes in regulatory sequences and coding regions in all five species to uncover whether genetic and/or epigenetic mechanisms underlie differences in expression levels between alleles, as seen in D. pachys, which may enable these animals to overcome potentially high loads of deleterious alleles. In summary, this study presents a unique opportunity to explore the evolution of asexual reproduction in animals, a centuries-old mystery in biology, whose molecular underpinning may provide new insights into molecular processes underlying aging in humans.

项目摘要通过性和重组对遗传多样化的真核创新提供了重要的自适应优势。尽管如此，人们认识到某些动物能够追溯到无性繁殖的历史至少1740年，整个动物王国多次独立地出现了无性恋。这过渡通常伴随着修饰的减数分裂和基因组组织。由于减数分裂缺陷是基础与年龄相关的人类生育能力下降，基因组不稳定性是衰老细胞的标志，研究了如何成功的无性谱系可以鉴于这些核心蜂窝程序的重大修改可以蓬勃发展提供有关衰老和不育的机制的新分子见解。为了表征无性繁殖的基因组特征，我们先前对基因组和 Evipopapter Pachys的转录组，来自异常持续的无性谱系的线虫估计起源于1800万年前。这项工作表明，D。Pachys缺乏关键的减数分裂基因，第一个（还原性）减数分裂分裂，使卵母细胞中的二倍体基因组无效地重构。令人惊讶的是，它的核基因组完全包装成一对染色体，我们表明的是来自所有祖先染色体的全部融合。但是，基因组组件仍然包含许多空白这限制了我们回答有关D. Pachys Evolution的关键问题的能力：基因组融合以及何时出现了删节的减数分裂，如何在没有遗传重组的情况下保持高序列多样性，哪种分子变化使向无性繁殖的过渡仍然是一个谜。我们建议利用长阅读测序和比较基因组学的力量来解决这些问题。在AIM 1中，我们将为D. Pachys生成高度连续的染色体水平基因组组件。这会揭示祖先染色体融合的模式，主要基因组重排是否可能排除减数分裂跨界以及染色体融合位点和端粒的性质。在AIM 2中，我们将生产染色体水平的基因组组件的另外四个孤子元及其最接近的性亲戚在同一系统发育进化枝中。这将允许对基因组结构进行比较分析，并启用分子遗传变化的进化重建与无性繁殖有关。在AIM 3中，我们将分析染色质的可及性以及所有五个物种的调节序列和编码区域的变化发现遗传和/或表观遗传机制是否是表达水平差异的基础等位基因，如D. pachys所示，这可能使这些动物能够克服潜在的高负荷有害等位基因。总而言之，这项研究提供了一个独特的机会来探索无性的演变动物的繁殖是一个数百年历史的生物学神秘，其分子的基础可能会提供新的对人类衰老的分子过程的见解。