09/11/2024
By Irma Silva

The Kennedy College of Sciences, Department of Biological Sciences, invites to you attend a Ph.D. Proposal Defense in Applied Biology by Thomas Wolfe entitled "The epigenetic landscape of duplicate genes and the influence of transposable elements."

Candidate: Thomas Wolfe
Degree: Doctoral
Date: Tuesday, Sept. 17
Time: 3:30 – 5:30 p.m.
Location: Southwick Hall 240

Committee Members:

  • Jennifer Fish, Associate Professor, Biological Sciences, University of Massachusetts Lowell
  • Teresa Lee, Assistant Professor, Biological Sciences, University of Massachusetts Lowell
  • Trevor Krabbenhoft, Assistant Professor, Biological Sciences, University of Buffalo

Brief Abstract:
Gene duplications are implicated in a wide variety of human diseases but are also important in the evolution of novel and adaptive functions. Most duplications are never fixed within a population and segregate as copy number variations that can contribute to complex neuropsychiatric disease and birth defects, in large part due to an attendant increased gene dosage. By contrast, for many duplicate genes that have reached fixation, there is strong evidence that their combined expression is initially closer to the level of the ancestral singleton, avoiding potential dosage imbalance. Though this expression reduction of one or both paralogs after duplication can be caused by the accumulation of regulatory mutations, a dosage imbalance created by duplication may have an immediate fitness cost before dosage-reducing mutations can help paralogs evade negative selection. Therefore, it has been proposed that epigenetic modifications—changes to DNA or DNA-associated proteins that regulate gene expression without changing the DNA sequence—facilitate this dosage balancing immediately after the duplication event by repressing expression of one or both duplicate copies. Consistent with this hypothesis, a few studies have demonstrated a reduction in the expression of paralogs shortly after duplication and a concomitant enrichment for repressive epigenetic modifications, as well as a reduction in enrichment for activating modifications. In our own research we have found enrichment for the repressive modification H3K9me3 in young duplicates in Dictyostelium discoideum and humans. This modification is strongly associated with transposable elements (TEs) in both species, as it often serves to silence these genomic elements, and we found young duplicates in both species enriched for the repressive mark to be inordinately close to or overlapping TEs. Importantly, the incidental spread of heterochromatin from TEs to proximal dosage-sensitive duplicates may shield them from selection by reducing expression of one or both duplicates. In my proposed research, I will investigate the degree to which the enrichment for TE-associated repressive modifications in young duplicates is conserved across animal species using publicly available genomic, epigenomic, and transcriptomic data in zebrafish, worm, fly and mouse genomes. I will also investigate the degree to which this phenomenon may contribute to the retention of dosage-sensitive duplicates using similar data from multiple primate lineages, along with recently published, comprehensive dosage-sensitivity predictions for all coding genes in the human genome. I hypothesize that the pattern of enrichment for TE-associated repressive modifications will be found across all species investigated, and that proximity to TEs and concomitant enrichment for repressive modifications will correlate with increased duplicability of dosage-sensitive genes in primates.