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Negative correlation between expression level and evolutionary rate of long intergenic non-coding RNAs

Monday, October 24, 2011 — Poster Session I

Noon – 2:00 p.m.

Natcher Conference Center



* FARE Award Winner


  • D Managadze
  • I Rogozin
  • D Chernikova
  • S Shabalina
  • E Koonin


Mammalian genomes contain numerous genes for long intergenic non-coding RNAs (lincRNAs). Functions of lincRNAs remain largely unknown but their evolution appears to be constrained by purifying selection. Obvious approach to gain insights into the mode of evolution and functional range of lncRNA is to compare them with better-characterized protein-coding genes, whose evolutionary rate shows universal negative correlation with expression: highly-expressed protein-coding genes are on average more conserved during evolution than genes with lower expression. This has been interpreted within the framework of the misfolding-driven protein evolution hypothesis according to which misfolding is the principal cost incurred by protein expression. We sought to determine whether lincRNAs follow the same evolutionary trend and detected moderate but statistically significant negative correlation between the evolutionary rate and expression level of human and mouse lincRNA genes. The magnitude of the correlation is similar to that of protein-coding genes. lincRNA expression level positively correlates with the predicted extent of lincRNA molecule folding, however the contributions of evolutionary rates and folding to expression level are independent. Thus, the anticorrelation between evolutionary rate and expression level appears to be general feature of gene evolution probably caused by similar deleterious effects of protein and RNA misfolding or other factors.

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