Biology subjects

Nick Colegrave

Publications and source records attributed to Nick Colegrave.

3 recordsLinked to original sources

bioRxiv2015

Fitness effects of new mutations in Chlamydomonas reinhardtii across two stress gradients

Most spontaneous mutations affecting fitness are likely to be deleterious, but the strength of selection acting on them might be impacted by environmental stress. Such stress-dependent selection could expose hidden genetic variation, which in turn might increase the adaptive potential of stressed populations. On the other hand, this variation might represent a genetic load and thus lead to population extinction under stress. Previous studies to determine the link between stress and mutational effects on fitness, however, have produced inconsistent results. Here, we determined the net change in fitness in 29 genotypes of the green algae Chlamydomonas reinhardtii that accumulated mutations in the near absence of selection for approximately 1,000 generations across two stress gradients, increasing NaCl and decreasing phosphate. We found mutational effects to be magnified under extremely stressful conditions, but such effects were specific both to the type of stress as well as to the genetic background. The detection of stress-dependent fitness effects of mutations depended on accurately scaling relative fitness measures by generation times, thus offering an explanation for the inconsistencies among previous studies.

Genetics↗

bioRxiv2015

Direct estimate of the spontaneous mutation rate uncovers the effects of drift and recombination in the Chlamydomonas reinhardtii plastid genome

Plastids perform crucial cellular functions, including photosynthesis, across a wide variety of eukaryotes. Since endosymbiosis, plastids have maintained independent genomes that now display a wide diversity of gene content, genome structure, gene regulation mechanisms, and transmission modes. The evolution of plastid genomes depends on an input of de novo mutation, but our knowledge of mutation in the plastid is limited to indirect inference from patterns of DNA divergence between species. Here, we use a mutation accumulation experiment, where selection acting on mutations is rendered ineffective, combined with whole-plastid genome sequencing to directly characterize de novo mutation in Chlamydomonas reinhardtii. We show that the mutation rates of the plastid and nuclear genomes are similar, but that the base spectra of mutations differ significantly. We integrate our measure of the mutation rate with a population genomic dataset of 20 individuals, and show that the plastid genome is subject to substantially stronger genetic drift than the nuclear genome. We also show that high levels of linkage disequilibrium in the plastid genome are not due to restricted recombination, but are instead a consequence of increased genetic drift. One likely explanation for increased drift in the plastid genome is that there are stronger effects of genetic hitchhiking. The presence of recombination in the plastid is consistent with laboratory studies in C. reinhardtii and demonstrates that although the plastid genome is thought to be uniparentally inherited, it recombines in nature at a rate similar to the nuclear genome.

Genomics↗

bioRxiv2015

Extensive de novo mutation rate variation between individuals and across the genome of Chlamydomonas reinhardtii

Describing the process of spontaneous mutation is fundamental for understanding the genetic basis of disease, the threat posed by declining population size in conservation biology, and in much evolutionary biology. However, directly studying spontaneous mutation is difficult because of the rarity of de novo mutations. Mutation accumulation (MA) experiments overcome this by allowing mutations to build up over many generations in the near absence of natural selection. In this study, we sequenced the genomes of 85 MA lines derived from six genetically diverse wild strains of the green alga Chlamydomonas reinhardtii. We identified 6,843 spontaneous mutations, more than any other study of spontaneous mutation. We observed seven-fold variation in the mutation rate among strains and that mutator genotypes arose, increasing the mutation rate dramatically in some replicates. We also found evidence for fine-scale heterogeneity in the mutation rate, driven largely by the sequence flanking mutated sites, and by clusters of multiple mutations at closely linked sites. There was little evidence, however, for mutation rate heterogeneity between chromosomes or over large genomic regions of 200Kbp. Using logistic regression, we generated a predictive model of the mutability of sites based on their genomic properties, including local GC content, gene expression level and local sequence context. Our model accurately predicted the average mutation rate and natural levels of genetic diversity of sites across the genome. Notably, trinucleotides vary 17-fold in rate between the most mutable and least mutable sites. Our results uncover a rich heterogeneity in the process of spontaneous mutation both among individuals and across the genome.

Genomics↗