# R35 Investigating rapidly evolving centromeres and their role in the reproductive isolation in mammals

> **NIH NIH R35** · EMORY UNIVERSITY · 2023 · $108,159

## Abstract

RESEARCH SUMMARY
Centromeric satellites and their binding partners are engaged in an ongoing evolutionary arms race such that
each side is continuously evolving to win the race. As a result, centromeres are one of the most divergent
genomic elements in populations, which ultimately stop exchanging genetic material and become two lineages.
Highly intractable nature of repetitive centromeric satellite harboring loci has been an impediment to
investigating the role of centromere evolution. The proposed research will test the role of centromere evolution
in lineage separation by utilizing 1) a state-of-the-art genomics-based approach to study satellite evolution 2)
geographically separated and partially reproductively isolated house mouse lineages, which serve as an ideal
system to study lineage separation 3) a candidate based evolutionarily guided approach to delineate
genetically complex process of the lineage separation.
Interestingly, binding of centromeric proteins at centromeric satellites varies between these lineages despite
the short evolutionary time after their split. This suggests that rapid divergence of centromeres in these two
evolving species have acquired functional differences, which can be measured. This work proposes that
rapidly evolving subspecies-specific variants of centromeric satellites and centromeric proteins result in
functional centromere variation between house mouse lineages. This hypothesis predicts that a cross between
these lineages generates chromosome segregation asymmetries in the hybrid meiosis due to “centromere
incompatibilities”. Taking advantage of the measurable functional divergence, this proposal aims to identify
lineage specific centromere features that contribute to the hybrid failure. Our multidisciplinary evolutionary
guided approach combines genomics, cell biology, and genetics to study incompatibilities between
centromeres of diverging lineages in the hybrid.
The proposed research will not only help in understanding the role of centromere evolution in lineage
separation but will also provide insights into the mechanisms of centromere evolution and inheritance. It will
also enhance our understanding of widespread chromosomal disorders resulting from impaired centromere
function. Centromere metabolism in cancerous cells involves expansion of satellite arrays and over-expression
of centromeric proteins and mimics centromere evolution in nature. Findings from our research will thus
provide insights into the process of centromere microevolution in cancers.

## Key facts

- **NIH application ID:** 10823914
- **Project number:** 3R35GM147558-02S1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Jitendra Thakur
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $108,159
- **Award type:** 3
- **Project period:** 2022-08-19 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10823914

## Citation

> US National Institutes of Health, RePORTER application 10823914, R35 Investigating rapidly evolving centromeres and their role in the reproductive isolation in mammals (3R35GM147558-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10823914. Licensed CC0.

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