Date of Completion

4-20-2016

Embargo Period

4-16-2026

Keywords

Genetics, centromeres, Drosophila

Major Advisor

Barbara Mellone

Associate Advisor

Rachel O'Neill

Associate Advisor

Michael O'Neill

Associate Advisor

John Malone

Associate Advisor

Kenneth Campellone

Field of Study

Genetics and Genomics

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

Centromeres mediate the conserved and essential process of chromosome segregation, yet centromeric DNA and the centromeric histone, CENP-A, are rapidly evolving. The rapid evolution of loop 1 (L1) of Drosophila CENP-A is thought to modulate the DNA-binding preferences of CENP-A to suppress centromere drive, the preferential transmission of chromosomes with expanded centromeric satellites during female meiosis. Consistent with this model, CENP-A from D. bipectinata (bip) fails to localize to D. melanogaster (mel) centromeres due to amino acid differences between mel and bip L1. Here, I show that this result is, in fact, due to the inability of the mel CENP-A chaperone, CAL1, to incorporate bip CENP-A into chromatin. Co-expression of bip CENP-A and bip CAL1 in mel cells restores centromeric localization, and similar findings apply to other Drosophila species. Furthermore, two co-evolving regions, CENP-A L1 and the CAL1 N-terminus, are identified as critical for lineage-specific CENP-A incorporation. Collectively, these data show that the rapid evolution of L1 regulates CAL1-mediated CENP-A assembly, suggesting an alternative mechanism for the suppression of centromere drive.

Download

Available for download on Thursday, April 16, 2026

COinS