NLM DIR Seminar Schedule

Abstract:

The availability of large numbers of bacterial genome sequences from the same species allows analysis of many polymorphisms of very recent origin. Data from the NCBI Pathogens project allows reconstruction of large numbers (over 100,000 for some species) of very recent single-nucleotide changes. I will present several studies of mutational hotspots and coding sequence evolution that are based on such data. The mutational phenomena include high transition rates at C5-methyl-cytosine, an extremely high C->A rate at certain N4-methylated cytosines, and tremendous acceleration of T->G mutation by preceding runs of G. Another study revealed positive selection for inactivation by nonsense mutations in dozens of Salmonella genes. Work on evolutionarily recent nonsynonymous changes, which have been only partially subjected to purifying selection, provides a window into purifying and positive selection on protein sequences that complements more distant comparisons. Analysis of recent changes affecting an E. coli clade that causes recurrent food-borne outbreaks revealed a likely genetic basis for this recurrence and a possible clue to the location of the reservoir of contamination.