Spontaneous Mutations Occur More in Highly Transcribed Regions in Daphnia.

Many molecular processes (eg replication, recombination, and transcription) use DNA as a template molecule, which may lead to an increase or decrease in the likelihood of spontaneous mutation and/or repair of mutations to this key information storage molecule. In the case of transcription, both positive and negative correlations with the likelihood of mutation have been observed across species, which have formed the basis of two proposed mechanistic models: transcription-associated mutagenesis and transcription-coupled repair. Here, we examine the patterns of spontaneous mutations in regions of low and high transcription in two species of the aquatic microcrustacean, Daphnia. By mapping events from a long-term mutation accumulation study (n = 66 lineages derived from nine different genotypes from three populations) with multiple, large-scale publicly available RNA-seq datasets, we find that mutations are more frequently observed in regions of high transcription in D. magna, as well as in the congener, D. pulex. The results are robust across mutation types (base substitutions, insertions, and deletions) and among transcriptional profiles (across developmental stages and environmental conditions). Overall, the positive correlation was robust to different methodological approaches and when controlling for other genomic features (like GC-content). Based on our observations, transcription-associated mutagenesis provides a more likely explanation for the positive relationship between mutation accumulation and transcription levels observed in Daphnia. Characterizing such patterns is important for understanding the evolution of genes, differentially expressed regions of the genome, and the mutation rate.