No support for the adaptive hypothesis of lagging-strand encoding in bacterial genomes

ABSTRACT Genes are preferentially encoded on the leading instead of the lagging strand of DNA replication in most bacterial genomes 1 . This bias likely results from selection against lagging-strand encoding, which can cause head-on collisions between DNA polymerases and RNA polymerases that induce transcriptional abortion, replication delay, and possibly mutagenesis 1 . But there are still genes encoded on the lagging strand, an observation that has been explained by a balance between deleterious mutations bringing genes from the leading to the lagging strand and purifying selection purging such mutations 2 . This mutation-selection balance hypothesis predicts that the probability that a gene is encoded on the lagging strand decreases with the detriment of its lagging-strand encoding relative to leading-strand encoding, explaining why highly expressed genes and essential genes are underrepresented on the lagging strand 3,4 . In a recent study, Merrikh and Merrikh proposed that the observed lagging-strand encoding is adaptive instead of detrimental, due to beneficial mutations brought by the potentially increased mutagenesis resulting from head-on collisions 5 . They reported empirical observations from comparative genomics that were purported to support their hypothesis 5 . Here we point out methodological flaws and errors in their analyses and logical problems of their interpretation. Our reanalysis of their data finds no evidence for the adaptive hypothesis.