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Biology subjects

Tuffaha, M. Z.

Publications and source records attributed to Tuffaha, M. Z..

2 recordsLinked to original sources

Evolutionary Rescue Promotes Mutators

The role of mutation rate in evolutionary rescue has been extensively explored, but little work has investigated how evolutionary rescue can promote mutators, lineages with higher mutation rates. Under complete linkage, we investigate the likelihood of evolutionary rescue on a mutator background that either emerges de novo or pre-exists in the population prior to a severe environmental change. If such an evolutionary rescue event occurs, the mutator lineage sweeps into the population, and thus the environmental stress has promoted mutators. Our findings indicate that mutation rate evolution can substantially boost rescue probabilities, but stronger mutators are most effective when the wildtype has a low mutation rate, while their advantage diminishes for higher wildtype mutation rates. Interestingly, at intermediate wildtype mutation rates, emerging mutators can be almost equally likely to sweep no matter how slowly or quickly the environment changes. However, at low wildtype mutation rates, mutators are only likely to sweep for very slow environmental changes due to the sequential nature of necessary mutations for such sweeps to occur. Finally, we show that pre-existing mutators can be significantly more likely to rescue the population compared to the wildtype, provided the wildtypes mutation rate is relatively low. This research opens new avenues for investigating mutator dynamics in response to environmental stress.

evolutionary biology↗

Non-hypermutator cancers access driver mutations through reversals in germline mutational bias

Cancer is an evolutionary disease driven by mutations in asexually-reproducing somatic cells. In asexual microbes, bias reversals in the mutation spectrum can speed adaptation by increasing access to previously undersampled beneficial mutations. By analyzing tumors from 20 tissues, along with normal tissue and the germline, we demonstrate this effect in cancer. Non-hypermutated tumors reverse the germline mutation bias and have consistent spectra across tissues. These spectra changes carry the signature of hypoxia, and they facilitate positive selection in cancer genes. Hypermutated and non-hypermutated tumors thus acquire driver mutations differently: hypermutated tumors by higher mutation rates and non-hypermutated tumors by changing the mutation spectrum to reverse the germline mutation bias.

cancer biology↗