CPCB Seminar: Vaughn Cooper, PhD

The Joint CMU-Pitt Ph.D. Program in Computational Biology and the Department of Computational and Systems Biology are pleased to present Dr. Cooper.

Visiting Associate Professor, Microbiology & Molecular Genetics, University of Pittsburgh, School of Medicine

Why Genome Regions Evolve at Different Rates: Lessons from Bacteria with Multiple Chromosomes

Friday, October 16
11:00 AM, 6014 BST3

Genome regions vary widely in their evolutionary rates. Not only may mutation rates differ among regions, but so too the effects of forces acting on mutations such as selection, recombination and genetic drift. One of our goals is to disentangle the contributions of these processes to evolutionary rates and patterns of gene organization, which would both improve the legibility of genomes and deepen our understanding of problems caused by deleterious mutations such as species extinction or somatic disease states like cancer and dementia. The remarkable lack of evidence for the nature of mutation, especially in prokaryotes, motivated a series of mutation-accumulation (MA) experiments using bacteria with multiple chromosomes, in which secondary, smaller chromosomes evolve much faster than the primary chromosome. MA experiments allow mutations to accumulate in many replicate lines in the near absence of selection, and whole-genome sequencing of evolved lines allows us to capture mutational distributions and any inherent biases.

Here, we describe genome-wide views of the molecular mutation spectrum in three distinct bacterial species (Burkholderia cenocepacia, Vibrio cholerae, and Vibrio fischeri) whose genomes all harbor multiple chromosomes but vary substantially in %GC content. All three species have low mutation rates with insertion-deletion mutations biased towards deletions. While the direction of mutation bias is consistent with the realized GC-content of all three organisms, realized GC-content is always higher than predicted by mutation pressure alone. We also observed variation in both the rates and spectra of mutations among chromosomes, and a significant elevation of G:C>T:A transversions in late-replicating regions that is consistent with greater oxidative damage later in the cell cycle. Most intriguing, mutation rates exhibit a wave-like pattern correlated with replication timing, again suggesting that the cellular state undergoes fluctuations that influence genome stability. Collectively, these findings support theory that genome architectures and content are shaped by systematic differences in both the origin and effects of mutations.