L. Tubiana, A.L. Bozic, C. Micheletti and R. Podgornik
Synonymous mutations reduce genome compactness in icosahedral ssRNA viruses
Biophysical Journal, 2015, 108 , 194-202
Link to online article
Cover article for the January 6 2015 issue of Biophysical Journal.
Link to accompanying "New and Notable" article by W. Gelbart and A. Ben-Shaul.
Recent studies have shown that single-stranded viral RNAs fold into more
compact structures than random RNA sequences with similar chemical
composition and identical length. Based on this comparison it has been
suggested that wild-type viral RNA may have evolved to be atypically
compact so as to aid its encapsidation and assist the viral assembly
process. In order to further explore the compactness selection hypothesis,
we systematically compare the predicted sizes of more than one hundred wild-type viral sequences with those of their mutants, which are evolved in
silico and subject to a number of known evolutionary constraints. In
particular, we enforce mutation synonynimity, preserve the codon-bias, and
leave untranslated regions intact. It is found that progressive
accumulation of these restricted mutations still suffices to completely
erase the characteristic compactness imprint of the viral RNA genomes,
making them in this respect physically indistinguishable from randomly
shuffled RNAs. This shows that maintaining the physical compactness of
the genome is indeed a primary factor among ssRNA viruses evolutionary
constraints, contributing also to the evidence that synonymous
mutations in viral ssRNA genomes are not strictly neutral.