Evolving mutation rate advances invasion speed of sexual species

Many species are shifting their ranges in response to global climate change. The evolution of dispersal during range expansion increases invasion speed, provided that a species can adapt sufficiently fast to novel local conditions. Mutation rates can evolve too, under conditions that favor an increased rate of adaptation. However, evolution at the mutator gene has thus far been deemed of minor importance in sexual populations due to its dependence on genetic hitchhiking with a beneficial mutation at a gene under selection, and thus its sensitivity to recombination. Here we use an individual-based model to show that the mutator gene and the gene under selection can be effectively linked at the population level during invasion. This causes the evolutionary increase of mutation rates in sexual populations, even if they are not linked at the individual level. The observed evolution of mutation rate is adaptive and clearly advances range expansion both through its effect on the evolution of dispersal rate, and the evolution of local adaptation. In addition, we observe the evolution of mutation rates in a spatially stable population under strong directional selection, but not when we add variance to the mean selection pressure. By this we extend the existing theory on the evolution of mutation rates, which is generally thought to be limited to asexual populations, with possibly far-reaching consequences concerning invasiveness and the rate at which species can adapt to novel environmental conditions as experienced under global climate change.

Bacterial DNA repair genes and their eukaryotic homologues: 2. Role of bacterial mutator gene homologues in human disease. Overview of nucleotide pool sanitization and mismatch repair systems.

Since the discovery of the first E. coli mutator gene, mutT, most of the mutations inducing elevated spontaneous mutation rates could be clearly attributed to defects in DNA repair. MutT turned out to be a pyrophosphohydrolase hydrolyzing 8-oxodGTP, thus preventing its incorporation into DNA and suppresing the occurrence of spontaneous AT-->CG transversions. Most of the bacterial mutator genes appeared to be evolutionarily conserved, and scientists were continuously searching for contribution of DNA repair deficiency in human diseases, especially carcinogenesis. Yet a human MutT homologue--hMTH1 protein--was found to be overexpressed rather than inactivated in many human diseases, including cancer. The interest in DNA repair contribution to human diseases exploded with the observation that germline mutations in mismatch repair (MMR) genes predispose to hereditary non-polyposis colorectal cancer (HNPCC). Despite our continuously growing knowledge about DNA repair we still do not fully understand how the mutator phenotype contributes to specific forms of human diseases.

The mutator gene swi8 effects specific mutations in the mating-type region of Schizosaccharomyces pombe.

The swi8+ gene of Schizosaccharomyces pombe appears to be involved in the termination step of copy synthesis during mating-type (MT) switching. Mutations in swi8 confer a general mutator phenotype and, in particular, generate specific mutations in the MT region. Sequencing of the MT cassettes of the h90 swi8-137 mutant revealed three altered sites. One is situated at the switching (smt) signal adjacent to the H1 homology box of the expression locus mat1:1. It reduces the rate of MT switching. The alteration at the smt signal arose frequently in other h90 swi8 strains and is probably caused by gene conversion in which the sequence adjacent to the H1 box of mat2:2 is used as template. This change might be generated during the process of MT switching when hybrid DNA formation is anomalously extended into the more heterologous region flanking the H1 homology box. In addition to the gene conversion at mat1:1, two mutations were found in the H3 homology boxes of the silent cassettes mat2:2 and mat3:3.

Increased rate of base substitution in a hamster mutator strain obtained during serial selection for gene amplification.

The pattern of mutations produced by a mutator gene (obtained during serial selection for amplification of the dihydrofolate reductase [dhfr] locus) shows a pronounced shift from that found in wild-type cells. The rate of certain types of base substitutions (particularly transitions) is dramatically increased, while gene rearrangements constitute a lower proportion of mutations. These data suggest a lower fidelity of the replication process in the mutator strain.