The evolution and genetics of recombination rate variation

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

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Principal Investigator: Kieran  Samuk
Organization: UNIVERSITY OF CALIFORNIA RIVERSIDE
Fiscal Year: 2024
Award: $382,958
Funding agency: National Institute of General Medical Sciences

PROJECT SUMMARY
Meiotic recombination is a fundamental aspect of reproduction in most eukaryotes. Recombination rate, i.e. the
number of crossovers per generation, is also a key modulator of genetic and evolutionary processes, having
profound effects on basic patterns of genetic inheritance, as well as high-level phenomena like adaptation and
speciation. Errors in recombination (e.g., nondisjunction) also contribute to a variety of human chromosomal
disorders, including trisomy 21 and Klinefelter syndrome. Despite its wide-ranging importance across many
domains of biology, we have a poor understanding of how and why recombination rate varies across biological
scales. Over the next five years, my lab will shed light on the genetic and evolutionary causes and
consequences of recombination rate variation by testing long-standing hypotheses using modern
genomic tools. This work will leverage empirical tools from two model systems, threespine sticklebacks and
Drosophila, and several new key genomic technologies. We will undertake four lines of research to test
hypotheses regarding the evolutionary drivers of recombination rate variation in natural populations. First, we
will explore the evolutionary drivers of recombination rate variation in a model vertebrate, threespine
sticklebacks, using gamete sequencing. Second, we will perform the first experimental test for the role of
structural variants in determining genome-wide recombination rate variation in vertebrates. Third, we will
perform a novel experimental test of the role of chromosomal inversions in adaptation using recent
advancements in CRISPR-mediated chromosomal engineering to create and “undo” chromosomal
arrangements in a Drosophila model species. Finally, we will develop modern and user-friendly statistical
methods for comparing recombination maps within and between species and populations. This research
program will greatly advance our understanding of the fundamental biology of meiotic recombination, create
myriad new resources and tools, and train personnel in cutting-edge techniques that span genomics,
computational biology, and evolutionary biology. These advances will be applicable across all domains of
biology, from understanding the evolution of diseases like SARS-CoV-2, to understanding the fundamental
mechanics of evolution in natural populations.

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