Evolutionary and functional dynamics of chimeric pseudogenes (φgenes)

Genome-associated changes during evolution followed by selection, facilitate development of new genes, gene families and even species. Pseudogenes (φgenes) generated during such genome rearrangements are often considered “dead on arrival” due to compromised expression arising from disruptive mutations or loss of regulatory elements. In an earlier study, we traced the expression of several φgenes, which challenges this notion. Here, we report segmental duplications at proximal genomic locations occasionally generate chimerism as a continuum of sequences from two or more genes, some of which involve intron fusions. These specific introns and flanking exons are likely to have co-evolved from ancestral parent genes. Notably, co-opting upstream regulatory sequences of 5′ parent gene may enable activation of chimeric φgenes, while modifications in 3′ sequences impart transcript stability. Few chimeric φgenes also harbor strong coding ORFs to be potentially translated into novel or truncated proteins retaining parental domains. Interestingly, chimeric φgenes are expressed only in human tissues, and display signatures of purifying selection. Examining potential functions associates ANAPC1P2 with genotoxic stress responses, while HYDIN2 may play a putative role in regulating cell cycle progression and neuronal differentiation. Taken together, our results suggest chimeric φgenes and their de novo functions may be relevant to speciation.