Swiss Institute for Experimental Cancer Research
Laboratory of Developmental Genomics
EPFL-SV-ISREC-UPDUB, SV2838A, Station 19
Abstracts (first author)
Origins and functional evolution of long non-coding RNAs in tetrapods
The search for molecular evolutionary innovations strongly relies on comparative analyses of gene repertoires, sequences and expression patterns. Such studies have been instrumental for our understanding of the genetic basis of lineage-specific phenotypes and of individual gene functions. However, these analyses have so far been restricted to protein-coding genes, and the contribution of other categories of genes, such as long noncoding RNAs (lncRNAs), has yet to be explored. Here, we use RNA sequencing to identify lncRNAs in eleven tetrapod species and we present the first large-scale evolutionary study of lncRNA repertoires and expression patterns. We identify ~11,000 primate-specific lncRNA families, which show evidence for selective constraint during recent evolution. These “young” lncRNA genes are lowly transcribed and predominantly expressed in testes, in agreement with the hypothesis that the permissive chromatin state of the testis favors the emergence of new genes. Interestingly, we also identify ~2,400 highly conserved lncRNAs, including ~400 genes that likely originated more than 300 million years ago. We find that lncRNAs, in particular ancient ones, are generally actively regulated and may predominantly function in embryonic development. Most lncRNAs evolve rapidly in terms of sequence and expression levels, but global patterns like tissue specificities are often conserved. We compared expression patterns of homologous lncRNA and protein-coding families across tetrapods to reconstruct an evolutionarily conserved co-expression network. This network, which surprisingly contains many lncRNA hubs, suggests potential functions for lncRNAs in fundamental processes like spermatogenesis or synaptic transmission, but also in more specific mechanisms such as placenta growth suppression through miRNA production.