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Special Bioinformatics Seminar Series: Structural Evolution of Long Non-Coding RNAs

Speaker: Peter Stadler , University Leipzig, Germany
Date: December 6 2011
Time: 11:30AM to 1:00PM
Location: Stata Center 32-G575
Host: Bonnie Berger, MIT

Structural Evolution of Long Non-Coding RNAs

Several recent studies have demonstrated that there are more than 10000
well-defined mRNA-like long non-coding RNAs produced from the human
genome. As a group, they have been found to be under significant but weak
stabilizing selection. Splice sites, on the other hand, are in many cases
retained over very large evolutionary time scales. They can be used to
predict, solely by means of comparative genomics methods, evolutionarily
well-conserved non-coding transcripts. These are conserved in their gene
structure but show little or no recognizable sequence conservation in
either their intronic or exonic sequences. While in flies the procedure is
conveniently based on intron predictions, in mammals one has to resort to
predictiong internal exons.

Conversely, we can use the conservation of splice site patterns of known
mlncRNAs to determine bounds on the gain and loss of mlncRNAs. Using the
GENCODE 7 set we find that of about 10000 human mlncRNAs, between 35% and
55% of the transcripts have at least one splicesite that, according to its
maxentscan score, is conserved in a distantly related mammal. Almost 70%
can be recovered in at least one of mouse, rat, dog, or cow. These numbers
are likely lower bounds limited by sensitivity and completeness of the
genome-wide underlying the analysis. While mlncRNAs evolve rapidly and
sequence level and are prone to frequent changes in gene structure,
the majority of human mlncRNAs appears to be evolutionarily old. Hundreds
of mlncRNAs, furthermore, appear to have Äoriginated before the divergence
of marsupials and placental mammals.

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