Background mutation rate from WGS

Question

[massa.kassa.sc3na]

Hi, everybody

Background: I'm investigating rapid selection of particular SNP (in bacteria) and I want to assess the probability of cell with that particular SNP to be present in the population prior to application of selective pressure.

Is it possible to assess what portion of observed variation in WGS of bacteria is due to inherent variation of the population from which the sample was taken, and what portion are the sequencing errors of the sequencing (DNA amplification / actual sequencing) steps?

Is there some SW which would allow to assess e.g. the mutation rate (or frequency of random mutation occurring in studied bacterial sp.) based on the whole genome sequencing reads?

Thanks for any advice, relevant SW / literature links, etc.

Answer 1

[LChart]

I'm not sure the mutation rate would help you very much. The units for a bacterial population would be something like "mutations per (kilo)base per passage" (where a "passage" would be one cycle of growing out a dish/plate). This means that the populations are different in terms of diversity after 100 passages versus after 10. As such the parent population of an evolutionary experiment is typically clonal (grown from a single cell) and also sequenced to determine the spectrum of that initial population.

For non-experimental selection (such as in pandemic monitoring or examining geographic diversity), coalescent theory is used to link populations back to inferred common ancestors; with individual mutations probabilistically assigned to branches of a phylogenetic tree. BEAST2 (https://www.beast2.org/tutorials/) is used for this, though typically not for selection - which can be added as a plugin or performed subsequent to phylogenetic inference (see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4750996/). You can also browse journals' "experimental evolution" section for papers that are similar in set up to your own situation: https://www.nature.com/subjects/experimental-evolution/ncomms