CAREER: Characterizing the rates and patterns of mutation and recombination in Old and New World monkeys CAREER: Characterizing the rates and patterns of mutation and recombination in Old and New World monkeys 1 PROJECT SUMMARY Overview. An understanding of the evolutionary forces and genetic processes that dictate the dynamics governing mutation is essential for illuminating the genetic underpinnings of disease and the chronology of primate evolution with current practice generally assuming a steady, clock-like accumulation of mutations over deep time. Yet, rates and patterns of mutation and recombination (which itself plays a critical role in dictating evolutionary outcomes) vary markedly between species. This observation not only casts doubt on the validity of the 'molecular clock', it also raises an important question: Given that the molecular machinery of cells is strongly conserved across primates, which factors underlie this species-level heterogeneity? Different hypotheses have been put forward, focusing on both the organismal and cellular level, but discerning amongst them has proven difficult in the absence of comparative genomic datasets of closely related species that differ only in the key implicated traits. Primates are a perfect model system in this regard: on the one hand, they exhibit a highly conserved cellular machinery and the limited differences that do exist in species-specific germline developmental processes (e.g., rates of spermatogenesis) are relatively well characterized (at least in those species used in biomedical research); on the other hand, a multitude of life history traits (e.g., age of puberty and reproduction), as well as correlated traits such as body size, metabolic rate, longevity, and the degree of sperm competition in different mating systems, persist across the primate clade. By performing a series of comparative analyses based on both publicly available data from great apes and Old World monkeys, as well as newly generated genomic resources for New World monkeys (titi monkeys and marmosets), this project aims to identify genomic features and quantify evolutionary processes that are driving these changes across primates. Given the nature of the work, the educational arm of this research will focus on teaching students the elementary skills of computational genomics. Intellectual Merit. As important outgroups to the ape lineage, novel insights into the rates and patterns of mutation and recombination in Old and New World monkeys will forward current debates centered around a potential gradual hominoid slowdown of the germline mutation rate (and thus a change of the 'molecular clock'). This knowledge is critically important to evaluate 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. Further, knowledge of the baseline levels of linkage disequilibrium in titi monkeys and marmosets will enable future genome-wide association studies in these species often used in behavioural research. Lastly, this uniform dataset across several non-human primates will provide the biomedical and evolutionary research communities with the necessary means to pursue new (and improved) research avenues in comparative genomics. Broader Impacts. As an active member of Google's Women Techmakers community aiming to provide visibility to women in computer science, the PI is already involved in a number of outreach activities to increase participation of female-identifying and non-binary students in STEM. In line with these efforts, this project will develop an educational framework to (i) teach undergraduates, particularly women and underrepresented minorities in STEM, the elementary skills of computational genomics by actively engaging them in explorative original research; (ii) offer mentored research opportunities to undergraduate and graduate students; and (iii) organize an annual symposium at which students will be able to showcase their work to the public. As the acquired computational skills are easily applicable to a wide-range of modern-day jobs, these activities will directly further the development of a diverse, globally competitive workforce. This project will also increase public engagement with science by (iv) setting-up a citizen-science project to engage the public in the study of Sonoran Desert genomic diversity; and (v) developing outreach materials for Arizona State Universitys "Ask a Biologist" website to promote scientific literacy among children and K-12 students. Taken together, the proposed activities will build a strong foundation of a firstgeneration early-stage female investigator in computational genomic research, education, and outreach.
|Effective start/end date||2/15/21 → 1/31/26|
- National Science Foundation (NSF): $1,177,451.00
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