A statistical analysis of the three-fold evolution of genomic compression through frame overlaps in prokaryotes

BACKGROUND: Among microbial genomes, genetic information is frequently compressed, exploiting redundancies in the genetic code in order to store information in overlapping genes. We investigate the length, phase and orientation properties of overlap in 58 prokaryotic species evaluating neutral and selective mechanisms of evolution. RESULTS: Using a variety of statistical null models we find patterns of compressive coding that can not be explained purely in terms of the selective processes favoring genome minimization or translational coupling. The distribution of overlap lengths follows a fat-tailed distribution, in which a significant proportion of overlaps are in excess of 100 base pairs in length. The phase of overlap – pairing of codon positions in complementary reading frames – is strongly predicted by the translation orientation of each gene. We find that as overlapping genes become longer, they have a tendency to alternate among alternative overlap phases. Some phases seem to reflect codon pairings reducing the probability of non-synonymous substitution. We analyze the lineage-dependent features of overlapping genes by tracing a number of different continuous characters through the prokaryotic phylogeny using squared-change parsimony and observe both clade-specific and species-specific patterns. CONCLUSION: Overlapping reading frames preserve in their structure, features relating to mutational origination of new genes, but have undergone modification for both immediate benefits and for variational buffering and amplification. Genomes come under a variety of different mutational and selectional pressures, and the structure of redundancies in overlapping genes can be used to detect these pressures. No single mechanism is able to account for all the variability observed among the set of prokaryotic overlapping genes but a three-fold analysis of evolutionary events provides a more integrative framework. REVIEWERS: This article was reviewed by Eugene Koonin, Marten Huynem, and Han Liang.