Chimeric genes as a source of rapid evolution in Drosophila melanogaster

Abstract

Chimeric genes form through the combination of portions of existing coding sequences to create a new open reading frame. These new genes can create novel protein structures that are likely to serve as a strong source of novelty upon which selection can act. We have identified 14 chimeric genes that formed through DNA-level mutations in Drosophila melanogaster, and we investigate expression profiles, domain structures, and population genetics for each of these genes to examine their potential to effect adaptive evolution. We find that chimeric gene formation commonly produces mid-domain breaks and unites portions of wholly unrelated peptides, creating novel protein structures that are entirely distinct from other constructs in the genome. These new genes are often involved in selective sweeps. We further find a disparity between chimeric genes that have recently formed and swept to fixation versus chimeric genes that have been preserved over long periods of time, suggesting that preservation and adaptation are distinct processes. Finally, we demonstrate that chimeric gene formation can produce qualitative expression changes that are difficult to mimic through duplicate gene formation, and that extremely young chimeric genes (d(S) < 0.03) are more likely to be associated with selective sweeps than duplicate genes of the same age. Hence, chimeric genes can serve as an exceptional source of genetic novelty that can have a profound influence on adaptive evolution in D. melanogaster.

Fig. 1.

Membrane-bound domains for CG31904. CG31904 combines three transmembrane helices from the predicted neurotransmitter transporter CG13796 and a single transmembrane helix from adult cuticular protein 1 (Acp1). The resulting peptide carries the long hydrocarbon chain from Acp1 that now faces inside rather than outside the cell.

Fig. 2.

Mid-domain breaks in CG18853. Full length of the peptide is shown with a black line. Conserved domains are depicted with shaded rectangles. CG18853 formed during a tandem duplication event that did not respect boundaries of genes or conserved protein domains. The parental peptide CG12822 carries a conserved domain of unknown function that is found in vertebrates as well as in multiple bacteria. The human ortholog of CG12822, Nef-associated protein 1, is a thioesterase that interacts with HIV protein Nef. The formation of CG18853 combined a portion of this domain with an FAD-binding domain to produce a new peptide that lies at the center of a selective sweep in D. melanogaster.

Fig. 3.

Local diversity π, measured as substitutions per site, surrounding CG18217 (solid line) fitted with the expectation after a selective sweep (dashed line). The fitted curve describes a selective sweep with s = 0.006 that occurred 20,000 years ago. The reduction in diversity spans 40 kb, which includes multiple gene sequences. The chimeric gene CG18217 lies at the center of the selective sweep.

Fig. 4.

Domain structure for CG18217. Full length of the peptide is shown with a black line. Conserved domains are depicted with shaded rectangles. The chimeric gene CG18217 was created when a tandem duplication united a portion of a DNA-repair gene CG4098 with a portion of the spindle-formation gene Spd-2. Chimeric gene formation has disrupted the Spd-2 protein and combined it with a NUDIX DNA-repair domain. The new 5′ end of the gene now confers expression in a greater number of tissues.

Fig. 5.

Local diversity π, measured as substitutions per site, surrounding CG18853 (solid line) fitted with the expectation after a selective sweep (dashed line). The fitted curve describes a selective sweep with s = 0.0025 that occurred 200,000 years ago. The reduction in diversity spans 45 kb, which includes multiple genes. The chimeric gene CG18853 lies at the center of the selective sweep.