Jorge Ruiz-Orera | Searcharxiv

arXiv2015

Origins of de novo genes in human and chimpanzee

The birth of new genes is an important motor of evolutionary innovation. Whereas many new genes arise by gene duplication, others originate at genomic regions that do not contain any gene or gene copy. Some of these newly expressed genes may acquire coding or non-coding functions and be preserved by natural selection. However, it is yet unclear which is the prevalence and underlying mechanisms of de novo gene emergence. In order to obtain a comprehensive view of this process we have performed in-depth sequencing of the transcriptomes of four mammalian species, human, chimpanzee, macaque and mouse, and subsequently compared the assembled transcripts and the corresponding syntenic genomic regions. This has resulted in the identification of over five thousand new transcriptional multiexonic events in human and/or chimpanzee that are not observed in the rest of species. By comparative genomics we show that the expression of these transcripts is associated with the gain of regulatory motifs upstream of the transcription start site (TSS) and of U1 snRNP sites downstream of the TSS. We also find that the coding potential of the new genes is higher than expected by chance, consistent with the presence of protein-coding genes in the dataset. Using available human tissue proteomics and ribosome profiling data we identify several de novo genes with translation evidence. These genes show significant purifying selection signatures, indicating that they are probably functional. Taken together, the data supports a model in which frequently-occurring new transcriptional events in the genome provide the raw material for the evolution of new proteins.

q-bio.GN↗

arXiv2014

Long non-coding RNAs as a source of new peptides

Deep transcriptome sequencing has revealed the existence of many transcripts that lack long or conserved open reading frames and which have been termed long non-coding RNAs (lncRNAs). Despite the existence of several well-characterized lncRNAs that play roles in the regulation of gene expression, the vast majority of them do not yet have a known function. Motivated by the existence of ribosome profiling data for several species, we have tested the hypothesis that they may act as a repository for the synthesis of new peptides using data from human, mouse, zebrafish, fruit fly, Arabidopsis and yeast. The ribosome protection patterns are consistent with the presence of translated open reading frames (ORFs) in a very large number of lncRNAs. Most of the ribosome-protected ORFs are shorter than 100 amino acids and usually cover less than half the transcript. Ribosome density in these ORFs is high and contrasts sharply with the 3UTR region, in which very often there is no detectable ribosome binding, similar to bona fide protein-coding genes. The coding potential of ribosome-protected ORFs, measured using hexamer frequencies, is significantly higher than that of randomly selected intronic ORFs and similar to that of evolutionary young coding sequences. Selective constraints in ribosome-protected ORFs from lncRNAs are lower than in typical protein-coding genes but again similar to young proteins. These results strongly suggest that lncRNAs play an important role in de novo protein evolution.

q-bio.GN↗