An integrated approach to understanding spontaneous mutation and natural selection in the Chlamydomonas genome

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Evolution by natural selection is fueled by genetic variation among individuals that ultimately originates from new mutations. Thus, the rate of appearance of new spontaneous mutations, whether they are beneficial or harmful and the magnitudes of their effects have profound consequences for the mode and speed of evolution. For example, if the rate of appearance of new beneficial mutations is very low, adaptation will frequently be limited by the supply of these mutations, whereas if the rate of beneficial mutations is high, adaptation will be limited by other processes, such as the speed with which natural selection can alter gene frequencies. Unfortunately, estimating mutational parameters has proved difficult, and, in spite of the importance of new mutations for evolution, there are few reliable estimates. We shall combine two approaches that aim to provide a fuller picture of the mutational process in our model system, the single-celled alga Chlamydomonas reinhardtii. Part of the difficulty in examining the supply of mutations is that natural selection operates in natural populations and removes deleterious mutations and increases the frequency of beneficial ones. Thus, the genetic differences that we observe within populations and between species are filtered and biased subsets of those mutations that arose in the first place. Our first approach will be to maintain replicate lines of C. reinhardtii for several hundred generations in conditions in which the effects of natural selection are minimised. This will allow us to examine the effects of the full spectrum of new mutations, not just those that pass through the filter of selection. We will then use state-of-the-art genome sequencing technologies to examine the complete genome sequences of a subset of these lines, which will allow us to measure directly the number and kinds of mutational changes at the DNA level. Taken together this information will provide us with a detailed picture of the fuel available to natural selection. Our second approach will also harness the power of whole genome sequencing to obtain a detailed picture of variation in the genome of C. reinhardtii sampled from a natural population. By comparing the amount and distribution of variation in different parts of the genome, we will be able to quantify how selection in natural conditions has acted on the mutations that originally generated the variation we observe. By comparing the genetic differences between different regions of the genome we will also be able to dissect the functional organisation of the genome, and determine which regions are constrained and so have remained relatively unchanged and which areas have more freedom to vary. We also plan to obtain the genome sequence of the closest relative of C. reinhardtii, C. incerta. By comparing the sequences of the C. reinhardtii and C. incerta genomes we shall be able to infer the principal adaptive changes in the genome between the two species. Answers to these questions will provide important insights in many areas of evolutionary biology, from helping us to understand why most eukaryotic species reproduce sexually to allowing us to predict whether the future responses of populations to environmental change is likely to be based on existing or new genetic variation.