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细胞（卵细胞和精子细胞）的自发突变，这些突变会传递给下一代。此外，在生殖细胞的产生过程中，父母的母系和父系衍生染色体中存在的变异通过称为重组的过程被改组成新的组合。近世纪以来，我们已经知道，在生命之树中，突变和重组的速率和模式有着显著的差异--然而，我们对潜在原因的了解仍然少得令人惊讶。通过进行一系列的比较基因组分析，这项研究的目的是确定基因组特征和量化的进化过程，推动这些变化在整个灵长类进化枝。更好地了解这些过程不仅在机械上而且在临床上都具有根本重要性，因为有害突变和异常重组可能导致导致遗传疾病和发育障碍的异常。该项目的教育部门侧重于多项活动，通过提供i）基于课程的本科研究经验（CURE），积极吸引学生参与探索性原创研究，ii）PI实验室的指导研究机会，以及iii）为女性识别和非二进制高中学生举办编码研讨会，教授生物信息学和计算基因组学的基本技能。传统上在这一领域代表性不足的群体。为了增加公众对科学的参与，该项目还将开展公民科学活动，并开发宣传材料，以促进K-12学生的科学素养。本研究的目标是通过实施简化的比较基因组学分析管道，表征灵长类进化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，该项目利用公开的数据和新产生的大猿以及旧世界和新世界猴子的基因组资源，i）描述家族之间和物种之间突变率的变化，ii）量化物种中的雄性突变偏差和父母年龄效应，iii）提高我们对灵长类动物的生活史特征和交配系统对突变率的影响的理解，以及iv）推断灵长类动物之间的重组率变化。所获得的知识将能够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，该奖项反映了NSF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进行评估，被认为值得支持的搜索.

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.