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This Week in PNAS: Apr 19, 2016

In the early, online edition of the Proceedings of the National Academy of Sciences, a team from the US and China explore the genome-wide mutation consequences of exposing Escherichia coli bacteria to low doses of an antibiotic called norfloxacin over long periods of time. With the help of whole-genome sequencing, the researchers tracked mutation accumulations in hundreds of replicate E. coli lines, representing eight sets of bugs treated with different sub-lethal doses of norfloxacin and transferred to new media daily for about two months. Their results suggest that E. coli's overall mutation rate increased with exposure to increasing antibiotic concentrations, apparently due to elevated activity by an error prone DNA polymerases, enhanced mutagenesis, diminished DNA damage repair, and other factors.

Researchers from the University of Houston and elsewhere investigate biological contexts in which newly acquired mutations might readily confer a benefit to bacteria for another PNAS paper. Starting with four mutations that have been shown to be beneficial in lab-grown E. coli, the team examined factors influencing their fitness effects in several phylogenetically diverse natural E. coli isolates. The resulting fitness shifts in recipient strains differed somewhat depending on their genetic or ecological similarities to the source, donor strain, the study authors note, though the recipient strain's original fitness levels had the most pronounced influence on the mutations' effects.

Finally, a Columbia University-, Genia Technologies-, and Harvard Medical School-led team describes the latest advances in its quest to develop an alpha-hemolysin protein-based nanopore device for doing electronically-based, single molecule sequencing-by-synthesis in real time. Building on a prior version of the approach that differentiated between DNA bases using polymer-tagged nucleotides, the investigators took the method a step further by developing slightly different forms of the tagged nucleotides using modified oligonucleotides. In additional to testing their ability to be incorporated into a growing DNA strand by a nanopore-tethered DNA polymerase, for example, they looked at the electrical signals produced as tagged strands of DNA move through the nanopore.