Postdoctoral Fellowship: PRFB: A fitness landscape for a satellite DNA causing unstable mitosis in Drosophila hybrids

Xiong, Tianzhu, Ithaca NY

Investigators

Abstract

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2024, Integrative Research Investigating the Rules of Life Governing Interactions Between Genomes, Environment, and Phenotypes. The fellowship supports research and training of the fellow that will contribute to the area of Rules of Life in innovative ways. In many organisms, chromosomes have big regions of repetitive sequences (repeats) with unknown roles. Complete repeat sequences can now be obtained, but interpreting this information is largely beyond existing analytical frameworks. This project will leverage a powerful concept, fitness landscape, to understand how different repeats influence the survival of individuals in fruit flies. This research will generate a much-needed mathematical theory on repeat evolution to make sense of the explosive growth of genome data. Through this research, the fellow will also contribute to broadening the accessibility of quantitative biology to undergraduate students. The fellow’s pedagogical activities will foster interest among biology students in quantitative reasoning, an essential skill for modern biological research. In fruit flies (Drosophila), a particular satellite repeat (359-bp) sits on the X chromosome of D. melanogaster but is absent in the closely related species D. simulans. This satellite fails to segregate during mitosis when placed in D. simulans’ eggs, suggesting that its mitotic stability requires specific embryonic regulation by D. melanogaster. In Aim 1, the fellow will use natural variation in D. simulans to map embryonic regulators of 359-bp. In Aim 2, the fellow will obtain a series of 359-bp alleles by a combination of CRISPR-induced deletion and natural alleles sampling. Then, the fellow will determine a quantitative map between 359-bp genotypes and their mitotic stability in interspecific hybrids. In Aim 3, a mathematical theory will be constructed based on this map to model the introgression dynamics of repeats between species. The fellow will receive new training in molecular genetic tools and bioinformatic methods on repetitive DNA. The fellow will recruit and mentor undergraduate students to participate in this research. The fellow will also develop teaching materials on introductory quantitative biology for first-year students at Cornell, which will be implemented in a workshop and distributed online to the broader biology community. 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.