  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.
