The Genome-Wide Rate and Spectrum of Spontaneous Mutations Differ Between Haploid and Diploid Yeast
This week we profile a recent publication in PNAS from Dr. Nathaniel Sharp (pictured)
and Dr. Sarah Otto at the University of British Columbia
Can you provide a brief overview of your lab’s current research focus?
Species vary substantially in how genetic material is transmitted from one generation to the next. Often genes from two individuals are combined through sex and shuffled by recombination, but some organisms get by without these steps. The number of genome copies per cell (“ploidy”) also varies — humans have two copies, but other organisms have just one, or many. In the Otto lab we’re interested in how these different reproductive strategies evolve and what the consequences are for adaptation.
What is the significance of the findings in this publication?
We wanted to know how the fundamental process of mutation was affected by the number of genome copies within a cell, both because this could tell us the evolutionary circumstances that favour one ploidy level over another and because it helps inform how different organisms could adapt to a changing environment. By comparing experimental yeast populations with one or two genome copies, we learned that ploidy affects mutations in a number of ways. Doubling the genome didn’t double the mutation rate — it only increased it by 43%, much less than we expected. Interestingly, yeast with two genome copies had a much higher rate of major genetic rearrangements; they appeared to have a much harder time “keeping track” of their chromosomes, often losing or gaining an extra chromosome.
What are the next steps for this research?
A surprising finding from this research was that mutations seemed to reduce the growth rate of diploid yeast more than haploid yeast, despite the fact that diploid cells retained a second, functional copy of most of the mutated genes. However, the haploid and diploid yeast in our experiment acquired different sets of mutations, making it hard to compare the effects of mutations between ploidy levels. To get around this we’re preparing to test the effects of a common set of mutations in both haploid and diploid cells, using genetic tools to convert haploids into diploids that have otherwise identical genomes. This will tell us more about how the effects of mutations respond to ploidy.
This research was funded by:
This research was supported by a Banting Postdoctoral Fellowship (to N.P.S.) and Natural Sciences and Engineering Research Council Discovery Grant RGPIN-2016-03711 (to S.P.O.).