Rapid Evolution of the Human Mutation Spectrum

Speaker Name: 
Kelley Harris, PhD
Speaker Title: 
Postdoctoral Research Fellow, Genetics
Speaker Organization: 
Stanford University Department of Genetics
Start Time: 
Friday, July 21, 2017 - 11:00am
End Time: 
Friday, July 21, 2017 - 12:00pm
Biomedical Sciences Building, Room 200, UC Santa Cruz
UC Santa Cruz Genomics Institute

Join us for the next in our BD2K Summer Up 2017 Speaker Series!


DNA is a remarkably precise medium for copying and storing biological information, with a mutation rate in humans of about 1e-8 per base pair per generation. This extraordinary  fidelity results from the combined action of hundreds of genes involved in DNA replication  and proofreading, and repair of spontaneous damage. Recent studies of cancer have shown that mutation of specific genes often leads to characteristic mutational "signatures''--i.e., increased mutation rates within particular sequence contexts.  We therefore hypothesized that  more subtle variation in replication or repair genes within natural populations might also lead to differences in mutational signatures. As a proxy for mutational input, we examined nucleotide variation across human and other great ape populations.  Remarkably we found that mutational spectra differ substantially among species, human continental groups and even, in some cases, between closely-related populations. Closer examination of one such signal, an increased rate of TCC>TTC mutations reported previously in Europeans, indicates a burst of mutations from about 15,000 to 2,000 years ago, perhaps due to the appearance, drift, and ultimate elimination of a genetic modifier of mutation rate.  Our results suggest the possibility of mapping modifiers of mutation rates within human populations and across species.

This public presentation is hosted by the UC Santa Cruz Genomics Institute and the BD2K Summer Undergraduate Research Training Program