Abstract
Background
Long considered to be the building block of life, it is now apparent that protein
is only one of many functional products generated by the eukaryotic genome. Indeed,
more of the human genome is transcribed into noncoding sequence than into protein-coding
sequence. Nevertheless, whilst we have developed a deep understanding of the relationships
between evolutionary constraint and function for protein-coding sequence, little is
known about these relationships for non-coding transcribed sequence. This dearth of
information is partially attributable to a lack of established non-protein-coding
RNA (ncRNA) orthologs among birds and mammals within sequence and expression databases.
Results
Here, we performed a multi-disciplinary study of four highly conserved and brain-expressed
transcripts selected from a list of mouse long intergenic noncoding RNA (lncRNA) loci
that generally show pronounced evolutionary constraint within their putative promoter
regions and across exon-intron boundaries. We identify some of the first lncRNA orthologs
present in birds (chicken), marsupial (opossum), and eutherian mammals (mouse), and
investigate whether they exhibit conservation of brain expression. In contrast to
conventional protein-coding genes, the sequences, transcriptional start sites, exon
structures, and lengths for these non-coding genes are all highly variable.
Conclusions
The biological relevance of lncRNAs would be highly questionable if they were limited
to closely related phyla. Instead, their preservation across diverse amniotes, their
apparent conservation in exon structure, and similarities in their pattern of brain
expression during embryonic and early postnatal stages together indicate that these
are functional RNA molecules, of which some have roles in vertebrate brain development.
