Strand-biased Gene Distribution in Bacteria Is Related to both Horizontal Gene Transfer and Strand-biased Nucleotide Composition

Although strand-biased gene distribution(SGD) was described some two decades ago,the underlying molecular mechanisms and their relationship remain elusive.Its facets include,but are not limited to,the degree of biases,the strand-preference of genes,and the influence of background nucleotide composition variations.Using a dataset composed of 364 non-redundant bacterial genomes,we sought to illustrate our current understanding of SGD.First,when we divided the collection of bacterial genomes into non-polC and polC groups according to their possession of DnaE isoforms that correlate closely with taxonomy,the SGD of the polC group stood out more significantly than that of the non-polC group.Second,when examining horizontal gene transfer,coupled with gene functional conservation(essentiality) and expressivity(level of expression),we realized that they all contributed to SGD.Third,we further demonstrated a weaker G-dominance on the leading strand of the non-polC group but strong purine dominance(both G and A) on the leading strand of the polC group.We propose that strand-biased nucleotide composition plays a decisive role for SGD since the polC-bearing genomes are not only AT-rich but also have pronounced purine-rich leading strands,and we believe that a special mutation spectrum that leads to a strong purine asymmetry and a strong strand-biased nucleotide composition coupled with functional selections for genes and their functions are both at work.