Origin of protein-coding genes from scratch. New coding regions may emerge de novo from noncoding genomic sequences. First, proto-open reading frames (proto-ORFs; thin blue bars) acquire mutations (point substitutions, insertions/deletions; yellow stars) that remove, bit by bit, frame-disrupting nucleotides (red wedges). Transcriptional activation of ORFs (through acquisition of promoters located in the 5′ flanking region) encoding proteins with potentially useful functions may allow for the evolution of novel protein-coding genes. (Large blue box) Functional exon, (pink right-angled arrow) TSS, (transparent pink box) untranslated 5′ sequence. Note that the transcriptional activation step may, alternatively, also precede the formation of complete functionally relevant ORFs.
