Evolution of relative reading frame bias in unidirectional prokaryotic gene overlaps.

Pairs of unidirectional (same strand) genes can overlap in one of two phases (relative reading frames). There is a striking bias in the relative abundance of prokaryotic gene overlaps in the two possible phases. A simple model is presented based on unidirectional gene overlaps evolving from nonoverlapping gene pairs, through the adoption of alternative start codons by the downstream genes. Potential alternative start codons within upstream gene sequences were found to occur at greater frequencies in one phase, corresponding to the most prevalent phase of gene overlaps. We therefore suggest that the phase bias of overlapping genes is primarily a consequence of the N-terminal extension of downstream genes through adoption of new start codons.