RNA CONFORMATION AS A POSSIBLE EVOLUTIONARY

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RNA CONFORMATION AS A POSSIBLE EVOLUTIONARY CONSTRAIN.

Y.A. Darikova 1 , E.A.Nikitina

1,3 , D.Yu.Sherbakov

1,2

1 Limnological Institute SB RAS, Irkutsk, Russia

2 Irkutsk State University

3 Irkutsk Regional Center for the Prevention and Fight against AIDS and infectious diseases e-mail: sherb@lin.irk.ru

*Corresponding author

Motivation and aim . Systematic comparative study of non-coding nucleotide sequences at population level or in a set of closely sister species may shed new light on forces influencing evolutionary transitions of genomes other then the fates of polypeptide functions in case of protein-coding sequences. Here we compare patterns of microevolution of several introns in a species flock of Baikalian snails belonging to genus

Baikalia to the patterns of evolution of a protein-coding gene from the same set of species/populations to show that transitions of tertiary structures of RNAs may be become important constrains on possible evolutionary transitions of some loci.

Furthermore, we show that at least in one case of mRNA (virus of hepatitis E, HEV) the tertiary structure may play important role in determining it’s essential biological properties and thus be of evolutionary importance.

Methods . Molluscan DNA sequences were obtained as described elsewhere (Darikova &

Shcherbakov, 2009). Tertiary structure of RNAs were obtained using Vienna RNA package and MFold. Phylogenetic inferences and analyses were performed using package ape in R. HEV full genome sequences were obtained from Genebank.

Results . One of the introns of the phosphofructokinase gene has been sequenced in seven species of endemic Baikalian gastropods of family Baicaliidae. The length of this intron differs even between sister species. Along with relatively few nucleotide substitutions numerous deletions and insertions accumulated. The number of deletions/insertions does not correlate to genetic distance between the species as estimated by comparing sequences of a mitochondrial fragment. Deduced tertiary structure differs markedly even between sister taxa although there is a consensus motif. Long RNA stems appearing and disappearing in course of evolution may contain regulatory RNAs and therefore the evolution of the intron may be non-neutral. There is no significant correlation between mutational distances estimated for pfk and from protein coding Cox I for the same species.

Two more introns were shown to evolve slower and more similar to Cox I.

Quantitative comparison of topologies of the consensus between the most probable conformations of paralogous RNAs shows that in case of non-coding sequences there are two distinctive patterns of evolution: conservation of a topology or it’s dramatic changes due to relatively few base substitutions. In case of HEV RNA it was shown that the viruses differing by only non-coding substitutions but causing contrasting clinic manifestations differ by their conformations dramatically.

Conclusion . Conformation of RNA of complementary to both coding and non-coding

DNA sequences may be independent and important evolutionary constrain and thus may be taken into account in phylogenetic and other inferences.

References

Darikova JA, Shcherbakov D.Y. Mol.Biol. (Moscow) 2009,43(5):838-844.

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