Properties of overlapping genes are conserved across microbial genomes

Abstract

There are numerous examples from the genomes of viruses, mitochondria, and chromosomes that adjacent genes can overlap, sharing at least one nucleotide. Overlaps have been hypothesized to be involved in genome size minimization and as a regulatory mechanism of gene expression. Here we show that overlapping genes are a consistent feature (approximately one-third of all genes) across all microbial genomes sequenced to date, have homologs in more microbes than do non-overlapping genes, and are therefore likely more conserved. In addition, the size, phase (reading frame offset), and distribution, among other characteristics, of overlapping genes are most consistent with the hypothesis that overlaps function in the regulation of gene expression. The upstream sequences and conservation of overlapping orthologs of two model organisms from the genus Prochlorococcus that have significantly different GC-content, and therefore different nucleotide sequences for orthologs, are also consistent with small overlapping sequence regions and programmed shifts in reading frame as a common mechanism in the regulation of microbial gene expression.

Figure 1.

Number of overlaps versus the total number of genes in the genome for all genomes in the National Center for Biotechnology Information bacteria database (as of May 3, 2003). Plasmids (circles) and chromosomes (squares) are identified by Eubacteria (black) or Archaebacteria (gray) domains. Properties are correlated at r² = 0.96.

Figure 2.

(A) Size frequency distribution of overlapping genes. Sizes, which are in-frame (i.e., multiples of three), are indicated with filled circles and out-of-phase overlaps have open circles, both with a solid line. The cumulative distribution is plotted as a dashed line. Individual tandem and antiparallel graphs (data not shown) have nearly identical patterns. (B) Distribution of tandem overlaps relative to respective phase maxima above six bases. Tandem in-phase observations were excluded because of few observations. (C) Distribution of antiparallel overlaps relative to respective phase maxima above six bases.