Genomic mechanisms of asexual reproduction

无性繁殖的基因组机制

• 批准号: 10289196
• 负责人: KRISTIN C GUNSALUS
• 金额: $ 23.78万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10289196
• 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

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 真核生物通过性别和重组实现的遗传多样性创新， 适应性优势。尽管如此，人们对一些动物能够无性繁殖的认识可以追溯到 至少在公元1740年，无性恋已经在动物王国中独立出现过多次。这 转变通常伴随着修改的减数分裂和基因组组织。由于减数分裂缺陷是 与年龄相关的人类生育能力下降，基因组不稳定是衰老细胞的标志，研究如何 成功的无性生殖谱系可以在这些核心细胞程序的重大修改的光中茁壮成长， 为衰老和不育的机制提供了新的分子见解。 为了表征无性繁殖的基因组特征，我们先前对基因组进行了测序， Diploscillopachys的转录组，一种来自异常持久的无性系的线虫，估计 起源于1800万年前本研究表明，D. Pachys缺乏关键的减数分裂基因， （减数）减数分裂，使得能够在卵母细胞中重建二倍体基因组而无需受精。 引人注目的是，它的核基因组被包装成一对染色体， 所有祖先染色体的完全融合。然而，基因组组装仍然包含许多空白 这限制了我们回答关于D的关键问题的能力。pachys进化：如何以及何时基因组融合， 减数分裂缩短，如何在没有遗传重组的情况下保持高水平的序列多样性， 是什么样的分子变化推动了向无性繁殖的转变仍然是一个谜。 我们建议使用长读测序和比较基因组学的力量来解决这些问题。 在目标1中，我们将产生一个高度连续的，染色体水平的基因组组装D。肥厚。这将 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 减数分裂交叉，染色体融合位点和端粒的性质。在目标2中，我们将 四个额外的孤雌生殖体及其最近的已知有性亲属的染色体水平基因组组装 属于同一个进化分支这将允许对基因组结构进行比较分析， 与无性繁殖有关的分子遗传变化的进化重建。在目标3中，我们 分析所有五个物种的染色质可及性以及调控序列和编码区的变化， 揭示是否遗传和/或表观遗传机制的差异表达水平之间 等位基因，如D. pachys，这可能使这些动物能够克服潜在的高负荷， 有害等位基因总之，这项研究提供了一个独特的机会来探索无性生殖的进化。 动物的繁殖，生物学上一个世纪的谜团，其分子基础可能提供新的 深入了解人类衰老的分子过程。