# The evolutionary and functional genomics of satellite DNA

> **NIH NIH R35** · UNIVERSITY OF ROCHESTER · 2022 · $421,050

## Abstract

Project summary
Eukaryotic genomes contain arrays of tandemly repeated non-coding sequences that we currently know little
about—satellite DNAs. Typically found near centromeres, telomeres, and on Y chromosomes, satellite DNAs
can comprise over 50% of some eukaryotic genomes. They are known to change rapidly in sequence and
genomic location, which can cause genetic incompatibilities between closely related species. The
misregulation of satellite DNA can have serious consequences for genomic stability and cancer formation.
Despite being a ubiquitous part of genomes and having important effects on cellular functions, the lack of
genetic, genomic, and molecular tools to study tandemly repeated sequences has stymied progress towards
understanding satellite DNA evolution and function. For example, satellite DNAs are particularly challenging to
sequence, assemble, and manipulate. Recent developments in sequencing and genome editing technologies
circumvent some of these problems. This proposal integrates genomic, molecular, and cytological methods to
study the evolutionary and functional genomics of satellite DNA in Drosophila genomes. The PI has developed
new genomic approaches and resources to study satellite DNA evolution with unprecedented resolution. The
PI will use a comparative genomics approach to study changes in satellite DNA sequence, abundance and
organization over evolutionary time and to determine the evolutionary forces driving these changes. This
proposal also aims to develop comprehensive population genetic models of satellite DNA evolution that take
into consideration different types of natural selection based on functional aspects of satellite DNAs studied in
this proposal and leverage empirical data about satellite DNA organization generated by the PI. Little is
currently known of satellite DNA function: the precise genetic manipulation of satellite DNAs with site-specific
gene editing approaches had not been possible in the past due to a lack of unique target sites. The PI has
used their assemblies of satellite loci to identify target sites and has successfully manipulated satellite DNA loci
using CRISPR/Cas9-based genome editing techniques. They have made precise genomic deletions and
duplications of satellite DNA in Drosophila melanogaster that they will use to test specific hypotheses about the
regulation, fitness effects, and selfish genetic behavior of satellite DNA. This proposal will also leverage the
new molecular genetic resources the PI created to manipulate satellite DNA expression to ask questions about
their functions in chromosome segregation and chromatin organization. These experiments will have broad
implications not only for genome evolution and speciation, but also for understanding the regulation of satellite
DNA in cancer and aging.

## Key facts

- **NIH application ID:** 10328694
- **Project number:** 2R35GM119515-06
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Amanda Marie Larracuente
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $421,050
- **Award type:** 2
- **Project period:** 2016-08-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328694

## Citation

> US National Institutes of Health, RePORTER application 10328694, The evolutionary and functional genomics of satellite DNA (2R35GM119515-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10328694. Licensed CC0.

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