The putative origin of replication in prokaryotic genomes can be locat
ed by a new method that finds short oligomers whose orientation is pre
ferentially skewed around the origin. The skewed oligomer method is sh
own to work for all bacterial genomes and one of three archaeal genome
s sequenced to date, confirming known or predicted origins in most cas
es and in three cases (H. pylori, M. thermoautotrophicum, and Synechoc
ystis sp.), suggesting origins that were previously unknown. In many c
ases, the presence of conserved genes and nucleotide motifs confirms t
he predictions. An algorithm for finding these skewed seven-base and e
ight-base sequences is described, along with a method for combining ev
idence from multiple skewed oligomers to accurately locate the replica
tion origin. Possible explanations for the phenomenon of skewed oligom
ers are discussed. Explanations are presented for why some bacterial g
enomes contain hundreds of highly skewed oligomers, whereas others con
tain only a handful. (C) 1998 Elsevier Science B.V. All rights reserve
d.