Biology subjects

Sharp, N. P.

Publications and source records attributed to Sharp, N. P..

2 recordsLinked to original sources

bioRxiv2018

The genome-wide rate and spectrum of spontaneous mutations differs between haploid and diploid yeast

By altering the dynamics of DNA replication and repair, alternative ploidy states may experience different rates and types of new mutations, leading to divergent evolutionary outcomes. We report the first direct comparison of the genome-wide spectrum of spontaneous mutations arising in haploid and diploid forms of the budding yeast. Characterizing the number, types, locations, and effects of thousands of mutations revealed that haploids were more prone to single-nucleotide and mitochondrial mutations, while larger structural changes were more common in diploids. Mutations were more likely to be detrimental in diploids, even after accounting for the large impact of structural changes, contrary to the prediction that diploidy masks the effects of recessive alleles. Haploidy is expected to reduce the opportunity for conservative DNA repair involving homologous chromosomes, increasing the insertion-deletion rate, but we found little support for this idea. Instead, haploids were more susceptible to particular single-nucleotide mutations in late-replicating genomic regions, resulting in a ploidy difference in the spectrum of substitutions. In diploids we detect mutation rate variation among chromosomes in association with centromere location, a finding that is supported by published polymorphism data. Diploids are Saccharomyces cerevisiae not simply doubled haploids; instead, our results predict that the spectrum of spontaneous mutations will substantially shape the dynamics of genome evolution in haploid and diploid populations.

evolutionary biology↗

bioRxiv2017

An experimental test of the mutation-selection balance model for the maintenance of genetic variance in fitness components

Despite decades of research, the factors that maintain genetic variation for fitness are poorly understood. Mutation selection balance will always contribute to standing variance, but it is unclear what fraction of the variance in a typical fitness component can be explained by mutation-selection balance and whether fitness components differ in this respect. In theory, the level of standing variance in fitness due to mutation-selection balance can be predicted using the rate of fitness decline under mutation accumulation, and this prediction can be directly compared to the actual standing variance observed. This approach allows for controlled statistical tests of the sufficiency of the mutation-selection balance model, and could be used to identify traits or populations where genetic variance is maintained by factors beyond mutation-selection balance. For example, some traits may be influenced by sexually antagonistic balancing selection, resulting in an excess of standing variance beyond that generated by deleterious mutations. To encourage the application of this approach, we describe the underlying theory and use it to test the mutation selection balance model for three traits in Drosophila melanogaster. We find some evidence for non-mutational variance in male mating success and female fecundity relative to larval viability, which is consistent with balancing selection on sexual fitness components. Finally, we discuss the theoretical and practical limitations to this approach, and discuss how to apply it successfully.

evolutionary biology↗