Predicting Statistical Properties of Open Reading Frames in Bacterial Genomes

Abstract

An analytical model based on the statistical properties of Open Reading Frames (ORFs) of eubacterial genomes such as codon composition and sequence length of all reading frames was developed. This new model predicts the average length, maximum length as well as the length distribution of the ORFs of 70 species with GC contents varying between 21% and 74%. Furthermore, the number of annotated genes is predicted with high accordance. However, the ORF length distribution in the five alternative reading frames shows interesting deviations from the predicted distribution. In particular, long ORFs appear more often than expected statistically. The unexpected depletion of stop codons in these alternative open reading frames cannot completely be explained by a biased codon usage in the +1 frame. While it is unknown if the stop codon depletion has a biological function, it could be due to a protein coding capacity of alternative ORFs exerting a selection pressure which prevents the fixation of stop codon mutations. The comparison of the analytical model with bacterial genomes, therefore, leads to a hypothesis suggesting novel gene candidates which can now be investigated in subsequent wet lab experiments.

Are Antisense Proteins in Prokaryotes Functional?

“…when 'mother gene' is conserved there is some tendency for conservation in the alternative strand (Wichmann and Ardern, 2019), but it is suggestive of a kind of purifying selection where mutations to biochemically similar amino acids are preferred in a subset of embedded antisense ORFs. It has previously been shown that long antisense ORFs appear more often in natural genomes than expected based on codon composition of annotated coding genes (Mir et al, 2012), another hint of selective processes preserving some antisense ORFs.…”

Protein Mis-Termination Initiates Genetic Diseases, Cancers, and Restricts Bacterial Genome Expansion

“…The longest coding exons in vertebrates and genes in bacteria are GC-rich, whereas the shortest genes are GC-poor [158]. The low GC bacterium Mycoplasma mycoides (GC content =24%) has 1,106 genes, and most of the genes have less than 20 codons [159]. Fusobacterium is associated with human oral cavities.…”

Phenotype ofhtgA(mbiA), a recently evolved orphan gene ofEscherichia coliandShigella, completely overlapping in antisense toyaaW

“…Silby & Levy, 2008;Tunca et al, 2009;Cheregi et al, 2012). However, the length distribution of overlapping open reading frames in bacteria suggest more of such genes exist (Mir et al, 2012).…”