Identification and ranking of pervasive secondary structures in positive sense single-stranded ribonucleic acid viral genomes
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Date
2018
Authors
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Publisher
University of the Western Cape
Abstract
The plasticity of single-stranded viral genomes permits the formation of secondary structures
through complementary base-pairing of their component nucleotides. Such structures have
been shown to regulate a number of biological processes during the viral life-cycle including,
replication, translation, transcription, post-transcriptional editing and genome packaging.
However, even randomly generated single-stranded nucleotide sequences have the capacity to
form stable secondary structures and therefore, amongst the numerous secondary structures
formed in large viral genomes only a few of these elements will likely be biologically
relevant. While it is possible to identify functional elements through series of laboratory
experiments, this is both excessively resource- and time-intensive, and therefore not always
feasible. A more efficient approach involves the use of computational comparative analyses
methods to study the signals of molecular evolution that are consistent with selection acting
to preserve particular structural elements. In this study, I systematically deploy a collection of
computationally-based molecular evolution detection methods to analyse the genomes of
viruses belonging to a number of ssRNA viral families (Alphaflexiviridae, Arteriviridae,
Caliciviridae, Closteroviridae, Coronavirinae, Flaviviridae, Luteoviridae, Picornaviridae,
Potyviridae, Togaviridae and Virgaviridae), for evidence of selectively stabilised secondary
structures. To identify potentially important structural elements the approach incorporates
structure prediction data with signals of natural selection, sequence co-evolution and genetic
recombination. In addition, auxiliary computational tools were used to; 1) quantitatively rank
the identified structures in order of their likely biological importance, 2) plot co-ordinates of
structures onto viral genome maps, and 3) visualise individual structures, overlaid with
estimates from the molecular evolution analyses. I show that in many of these viruses
purifying selection tends to be stronger at sites that are predicted to be base-paired within
secondary structures, in addition to strong associations between base-paired sites and those
that are complementarily co-evolving. Lastly, I show that in recombinant genomes breakpoint
locations are weakly associated with co-ordinates of secondary structures. Collectively, these
findings suggest that natural selection acting to maintain potentially functional secondary
structures has been a major theme during the evolution of these ssRNA viruses.
Description
Philosophiae Doctor - PhD
Keywords
Viral life-cycle, Deoxyribonucleic-acid (ssDNA), Viral genomes, Viral evolution