Novel protein-coding genes can arise either through re-organization of 
pre-existing genes or de novo. Processes involving re-organization of 
pre-existing genes, notably after gene duplication, have been extensively 
described. In contrast, de novo gene birth remains poorly understood, mainly 
because translation of sequences devoid of genes, or 'non-genic' sequences, is 
expected to produce insignificant polypeptides rather than proteins with 
specific biological functions. Here we formalize an evolutionary model according 
to which functional genes evolve de novo through transitory proto-genes 
generated by widespread translational activity in non-genic sequences. Testing 
this model at the genome scale in Saccharomyces cerevisiae, we detect 
translation of hundreds of short species-specific open reading frames (ORFs) 
located in non-genic sequences. These translation events seem to provide 
adaptive potential, as suggested by their differential regulation upon stress 
and by signatures of retention by natural selection. In line with our model, we 
establish that S. cerevisiae ORFs can be placed within an evolutionary continuum 
ranging from non-genic sequences to genes. We identify ~1,900 candidate 
proto-genes among S. cerevisiae ORFs and find that de novo gene birth from such 
a reservoir may be more prevalent than sporadic gene duplication. Our work 
illustrates that evolution exploits seemingly dispensable sequences to generate 
adaptive functional innovation.