CAREER: Characterizing the rates and patterns of mutation and recombination in Old and New World monkeys

基因组——生命的蓝图——随着时间的推移而进化。这种进化变化的基础是生殖系（卵子和精子细胞）的自发突变，这些突变会遗传给下一代。此外，在生殖细胞的形成过程中，存在于亲本和父本衍生染色体中的变异通过一个称为重组的过程被洗牌成新的组合。近一个世纪以来，我们已经知道，在生命之树上，突变和重组的速率和模式存在显著差异，然而，我们对其潜在原因知之甚少。通过进行一系列比较基因组分析，本研究旨在确定基因组特征并量化驱动灵长类进化支系这些变化的进化过程。更好地了解这些过程是至关重要的，不仅在机械上，而且在临床上，因为有害突变和异常重组可能导致导致遗传疾病和发育残疾的异常。该项目的教育部门侧重于多种活动，通过提供i)基于课程的本科研究经验（CURE），积极吸引学生进行探索性原创研究，ii) PI实验室的指导研究机会，以及iii)为女性识别和非二元高中学生（传统上在该领域代表性不足的群体）提供编码讲习班，教授生物信息学和计算基因组学的基本技能。为了增加公众对科学的参与，本项目还将组织公民科学活动，并编写外联材料，以提高K-12学生的科学素养。本研究的目的是通过实施一个流线型的比较基因组学分析管道来描述在灵长类进化分支中突变和重组的速率和模式变化的程度和时间尺度。为此，该项目利用公开可用的数据和新生成的类人猿以及新旧世界猴的基因组资源，1)描述家族间和物种间突变率的变化，2)量化物种中的雄性突变偏见和亲代年龄效应，3)提高我们对生活史特征和性交配系统对灵长类突变率的影响的理解。iv)推断灵长类动物之间的重组率差异。所获得的知识将有助于评估竞争性进化模型，旨在解释灵长类动物之间观察到的异质性，并阐明潜在的种群水平和遗传因素，最终导致对灵长类动物进化年表的更好理解。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Genomes – the blueprints of life – evolve over time. Underlying this evolutionary change are spontaneous mutations in the germline (egg and sperm cells) that are passed on to the next generation. In addition, during the creation of germ cells, variations present in a parent's maternally and paternally derived chromosomes are shuffled into novel combinations by a process called recombination. For nearly a century, we have known that rates and patterns of mutation and recombination vary markedly across the tree of life – yet, we still know surprisingly little about the underlying causes. By performing a series of comparative genomic analyses, this research aims to identify genomic features and quantify evolutionary processes that are driving these changes across the primate clade. Gaining a better understanding of these processes is of fundamental importance, not only mechanistically, but also clinically, as deleterious mutations and aberrant recombination can cause abnormalities that lead to genetic disease and developmental disabilities. The educational arm of this project focuses on multiple activities to teach the elementary skills of bioinformatics and computational genomics by offering i) a course-based undergraduate research experience (CURE) that actively engages students in explorative original research, ii) mentored research opportunities in the PI's lab, and iii) coding workshops for female-identifying and non-binary high school students, groups traditionally underrepresented in this field. To increase public engagement with science, this project will additionally construct citizen-science activities and develop outreach materials to promote scientific literacy among K-12 students.The goal of this research is to characterize the extent and time-scale at which changes in the rates and patterns of mutation and recombination have evolved across the primate clade by implementing a streamlined comparative genomics analysis pipeline. To this end, the project takes advantage of both publicly available data and newly generated genomic resources for great apes as well as Old and New World monkeys to i) characterize the variation in mutation rate among families and between species, ii) quantify male mutation biases and parental age effects in the species, iii) improve our understanding of the influence of life history traits and sexual mating systems on mutation rate in primates, and iv) infer recombination rate variation across primates. The gained knowledge will enable the evaluation of competing evolutionary models aiming to explain the heterogeneity observed amongst primates, and elucidate the underlying population-level and genetic factors at play, ultimately leading to an improved understanding of the chronology of primate evolution.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.