74T Poster - Evolutionary Genetics
Thursday June 09, 8:30 PM - 9:15 PM

Authors:
Sung-Ya Lin ¹; Hannah Futeran ¹; Mia Levine ^1,2

Affiliations:
1) Department of Biology, School of Arts & Sciences, University of Pennsylvania, Philadelphia, PA; 2) Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

Keywords:
Coevolution

Chromosome ends pose two primary threats to genome integrity: the erosion of unique DNA sequence and inappropriate DNA repair into lethal end-to-end chromosome fusions. Specialized telomere binding proteins combat these threats by 1) adding telomere-specific repetitive DNA to the chromosome ends and 2) protecting chromosome ends from telomere fusions. Although these telomere functions are essential in all eukaryotes, many telomere proteins evolve rapidly. Across the Drosophila species group, nearly half of the proteins required for telomere functions evolve rapidly under positive selection. Two such proteins, HOAP and HipHop, are essential components of the Drosophila end-protection complex – homozygous null mutations in either one result in lethal telomere fusions. These two proteins physically interact and HipHop depends on HOAP for recruitment to the telomere. We hypothesize that HipHop coevolves with HOAP to maintain this physical interaction and ultimately, to ensure its own recruitment to, and protection of, chromosome ends. To test this hypothesis, we transgenically replaced the native D. melanogaster HipHop with the highly diverged version from its close relative, D. yakuba (“HipHop[yak]”). We discovered that HipHop[yak] flies are homozygous lethal at the pupal-to-adult transition. Immunofluorescence on mitotic chromosomes from larval brains revealed that HipHop[yak] is depleted at telomeres compared to the control, HipHop[mel]. These cells also exhibited high rates of telomere associations, which are typical of the fused telomeres found in the HipHop null mutant. These data suggest that HipHop[yak] behaves as a loss-of-function allele. To determine if lethality results from disrupted coevolution between HOAP and HipHop, we swapped HOAP from D. yakuba (“HOAP[yak]”) into the D. melanogaster fly encoding only HipHop[yak]. Remarkably, HOAP[yak] restored HipHop[yak] protein localization to telomere ends, restored telomere end-protection from fusions, and restored adult viability. These results reveal that recruitment of HipHop to telomeres requires the conspecific HOAP and support our hypothesis that HipHop coevolves with HOAP to maintain telomere integrity. We suspect that HipHop evolves to “keep up” with an ever-evolving HOAP, which we previously showed evolves adaptively to restrict selfish telomeric retrotransposons.