Abstract
BackgroundViruses undergo extensive evolutionary selection for efficient replication which effects, among others, their codon distribution. In the current study, we aimed at understanding the way evolution shapes the codon distribution in early vs. late viral genes in terms of their expression during different stages in the viral replication cycle. To this end we analyzed 14 bacteriophages and 11 human viruses with available information about the expression phases of their genes.ResultsWe demonstrated evidence of selection for distinct composition of synonymous codons in early and late viral genes in 50% of the analyzed bacteriophages. Among others, this phenomenon may be related to the time specific adaptation of the viral genes to the translation efficiency factors involved at different bacteriophage developmental stages. Specifically, we showed that the differences in codon composition in different temporal gene groups cannot be explained only by phylogenetic proximities between the analyzed bacteriophages, and can be partially explained by differences in the adaptation to the host tRNA pool, nucleotide bias, GC content and more.In contrast, no difference in temporal regulation of synonymous codon usage was observed in human viruses, possibly because of a stronger selection pressure due to a larger effective population size in bacteriophages and their bacterial hosts.ConclusionsThe codon distribution in large fractions of bacteriophage genomes tend to be different in early and late genes. This phenomenon seems to be related to various aspects of the viral life cycle, and to various intracellular processes. We believe that the reported results should contribute towards better understanding of viral evolution and may promote the development of relevant procedures in synthetic virology.
Highlights
Viruses undergo extensive evolutionary selection for efficient replication which effects, among others, their codon distribution
Bacteriophage early and late genes tend to have different compositions of synonymous codons Genome level information about the different viruses analyzed in this study, like their hosts, number of genes, gene lengths and Effective number of codons (ENC), is displayed in Additional file 1: Table S1 and Figure S1
In order to compare the synonymous codons usage in early and late genes, each coding sequence was represented by its relative synonymous codons frequencies (RSCF) - a 61 dimensional vector expressing each sense codon by its frequency in that sequence normalized relative to the frequencies of other synonymous codons coding for the same amino acids (AA)
Summary
Viruses undergo extensive evolutionary selection for efficient replication which effects, among others, their codon distribution. We aimed at understanding the way evolution shapes the codon distribution in early vs late viral genes in terms of their expression during different stages in the viral replication cycle. To this end we analyzed 14 bacteriophages and 11 human viruses with available information about the expression phases of their genes. The early genes are expressed following the entry into the host cell and code typically for non-structural proteins that are responsible for different regulatory functions in processes such as: viral DNA replication, activation of late genes expression, trans-nuclear. During the initial stages of phage development the decoding rates in early genes were found to be higher than the decoding rates in late genes; in more progressive viral cycles an opposite trend was demonstrated [17]
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