Research in the Ness lab
The cliche goes: mutation is the ultimate source of all genetic variation. In my research I use experimental evolution to study the process of mutation and its consequences for fitness. Our research has shown that the mutation rate between individuals can vary up to 7-fold. In addition - and although there is little evidence for variation in mutation rate at large genomic scales - we found that sequence of the DNA surrounding a single site in the genome can alter its mutation rate by 17-fold.
My lab is currently working with experimental lines of Chlamydomonas reinhardtii to look at how these new mutations have affected their fitness. Although selection keeps only the best mutations, the vast majority of mutations have either no effect or are actually harmful because they break otherwise functional genes. By measuring the fitness of mutated experimental lines we are determining the fitness effects of hundreds of spontaneous mutations. We also combine natural whole-genome sequences with the experimental data to understand how the function, gene expression, and connections between genes predict the fitness effects of new mutations.
The whole reason that sex exists is to shuffle our genetic material through the processes of segregation and recombination. Recombination is important because it brings distinct beneficial mutations together into the same individual, which reduces interference between competing mutations. It can also unlink a beneficial mutation from nearby harmful mutations, which allows for that beneficial mutation to be selected more effectively. In my lab, we are combining experimental recombinant lines with whole genome sequencing to study the nature of recombination in Chlamydomonas reinhardtii. This project seeks to answer some fundamental questions about recombination rate variation:
Does recombination rate vary between individuals?
To what extent does recombination rate vary across the genome and is this landscape consistent across individuals?
What genomic properties and sequence motifs predict the rate of recombination at fine scales?
Drift vs Selection
If recombination allows more efficient selection for adaptive mutations and against harmful mutations, we expect the signature of selection in the genome to be stronger where there is more recombination. Using the unique resources we have generated describing mutation and recombination, we are working to understand how recombination changes the balance of genetic drift and selection in the genome of Chlamydomonas reinhardtii. In this framework, we are studying the evolution of genome size and base composition.
A major focus of research in evolution and biodiversity is to understand the genetic changes underlying variation within and between species. Patterns of genetic differentiation in the genome can provide insights into speciation, hybridization and local adaptation. Gene flow and recombination homogenize genetic variation between populations. When total migration is reduced, differentiation will accumulate across the entire genome. In contrast, local adaptation causes differentiation only at loci beneficial to the local environment. In some instances, co-adapted gene complexes are kept together in islands where recombination is suppressed. The general importance of such chromosomal rearrangements for maintaining adaptive variation and their impact on speciation remains an open question. We are working to extend our understanding of adaptation in Chlamydomonas by sampling algae in their natural habitat and studying the traits and genes that make them adapted to their local environment. This work involves field work, population genomics and genetic trait mapping.