Mutation Rate Evolution: The Changing Origin Story of Genetic Variation
The genetic information that encodes the blueprint for life on earth is changing all the time. When a child is born, its genome inevitably contains copying mistakes, or mutations, that make it different from either of its parents, and if the child successfully reproduces, those new mutations can become raw material for distinctive new biological traits. Using the vast amounts of genome sequence data that are being produced by the genomics community every year, my lab studies how the gene pools of humans and other species are evolving over time. We mathematically model how natural selection and random genetic drift shape the variation that currently defines us, and we are especially interested in deducing how genomic mutability itself might be changing.
Although all humans are closely related to each other and have a similar need to safeguard their DNA from damage, we have found surprising differences between the types of new mutations that tend to occur in different populations. We can think of the human genome as a document composed of short DNA "words," and we can show that some words mutate more often in Europeans than in Africans and vice versa.
The fact that different DNA damage and repair processes tend to have different target sequence preferences suggests that every population experiences a slightly different suite of forces that assault and safeguard its DNA. However, it is not clear what drives these changes in replication fidelity and whether these mysterious forces are linked to particular health outcomes such as cancer and aging, which can both be accelerated when the integrity of genetic material is compromised. Using computational analyses of the genetic variation that exists within humans and other species, we aim to deduce what is causing the mutation process to evolve and what health outcomes might be evolving in concert.