Codon bias and base composition are poor indicators of horizontally transferred genes

Horizontal gene transfer is now recognized as an important mechanism of evo lution. Several methods to detect horizontally transferred genes have been suggested. These methods are based on either nucleotide composition or the failure to find a similar gene in closely related species, Genes that evolv e vertically between closely related species can be divided into those that retain homologous chromosomal positions (positional orthologs) and those t hat do not. By comparing open reading frames in the Escherichia coli and Sa lmonella typhi genomes, we identified 2,728 positional orthologs since thes e species split 100 MYA. A group of 1,144 novel E. coli genes were unusuall y diverged from their S. typhi counterparts. These novel genes included tho se that had been horizontally transferred into E. coli, as well as members of gene pairs that had been rearranged or deleted. Positional orthologs wer e used to investigate compositional methods of identifying horizontally tra nsferred genes. A large number of E, coli genes with normal nucleotide comp osition have no apparent ortholog in S. typhi, and many genes of atypical c omposition do, in fact, have positional orthologs. A phylogenetic approach was employed to confirm selected examples of horizontal transmission among the novel groups of genes. Our analysis of 80 E. coli genes determined that a number of genes previously classified as horizontally transferred based on base composition and codon bias were native, and genes previously classi fied as native appeared to be horizontally transferred. Hence, atypical nuc leotide composition alone is not a reliable indicator of horizontal transmi ssion.