# Genetic Conflict Shapes Centromeres and Heterochromatin

> **NIH NIH R01** · FRED HUTCHINSON CANCER CENTER · 2021 · $203,198

## Abstract

PROJECT SUMMARY
Chromosome segregation is an essential process. The key chromosomal sites that
ensure proper segregation of chromosomes are centromeres, which bind microtubules
that pull chromosomes or chromatids apart during meiosis and mitosis. Centromere
function is thus essential for chromosome segregation. Defective centromeres can lead
to aneuploidy, infertility, and birth defects like Down’s syndrome. Despite the
conservation of the chromosome segregation process, centromeric proteins like CenH3,
which bind centromeric DNA to assemble microtubule-recruiting kinetochores, evolve
rapidly between closely related species. Their rapid evolution is unexpected and could
imperil the fidelity of the chromosome segregation process. We previously proposed that
this rapid evolution occurs due to ‘centromere-drive’, i.e., competition between
chromosomes during female meiosis, in which only one of four meiotic products is
chosen to be the egg pronucleus. Using an approach that combines insights from
evolutionary genetics and cell biology, and state-of-the-art genome engineering tools, we
propose to test this model of genetic conflict in Drosophila species. Furthermore, based
on our finding of recurrent duplication of CenH3 in Drosophila species, we will test
whether somatic versus germline centromeric functions have different functional
constraints, which are easiest to resolve via gene duplication and specialization of
CenH3 genes.

## Key facts

- **NIH application ID:** 10411940
- **Project number:** 6R01GM074108-17
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Harmit S. Malik
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $203,198
- **Award type:** 6
- **Project period:** 2005-07-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10411940

## Citation

> US National Institutes of Health, RePORTER application 10411940, Genetic Conflict Shapes Centromeres and Heterochromatin (6R01GM074108-17). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10411940. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*