On 2015 Sep 04, Casey M Bergman commented:

Orignally posted at PubPeer: https://pubpeer.com/publications/B37A9BD035CAEA3EEE79C48DDB0378

This paper provides a nice example of natural selection operating on a new gene duplicate at the Resistance to dieldrin (Rdl) locus in in D. melanogaster. Starting with an amino acid variant that is known to confer resistence to the insecticide dieldrin, the authors query whole genome sequences in the Drosophila Genetic Reference Panel (DGRP) [1] and find four strains that contain the resistance mutation. In three of the four strains, the resistance mutation is found unexpectedly in a heterozygous condition. The DGRP strains are highly inbred but are known to contain regions of residual heterozygosity scattered throughout the genome that could arise from incomplete inbreeding or segmental duplication.

By genotyping the offspring of "heterozygous" stocks, the authors find that 100% of progeny retain the heterozygous state, consistent with a segmental duplication. Analysis of the depth of sequence coverage in "heterozygous" strains confirms a 2-fold increase in the depth of coverage for a ~110 kb region containing Rdl and several other genes. The segmental duplication is flanked by two Roo transposable elements, suggesting it arose by ectopic recombination between repetitive sequences. The outcome of the duplication is that one duplicate contains the resitance allele and the other duplicate contains the susceptibility allele. Both copies are expressed. Transgenic analysis confirmed that the cause of the resistence allele is due to a single amino acid change in the Rdl gene only.

This paper shows how a newly arising allele with partial dominance can achieve a state of "permanant heterozygosis" by segmental duplication, conferring immediate adaptive advantage via the new allele while also retaining ancestral function via the old allele. This result nicely confirms a theoretical model developed by Spofford (1969) [2] (not cited in the current work) to explain selective forces that would govern the fixation of a new, polymorphic segmental gene duplicate. This work also shows that the "residual heterozygosity" in the DGRP lines may be more than just background noise from the vagaries of inbreeding, and may in fact point to many other functional segmental duplications in these lines.

[1] Mackay, Trudy FC, et al. "The Drosophila melanogaster genetic reference panel." Nature 482.7384 (2012): 173-178. http://www.nature.com/nature/journal/v482/n7384/full/nature10811.htm

[2] Spofford, Janice B. "Heterosis and the evolution of duplications." American Naturalist (1969): 407-432. http://www.jstor.org/stable/2458991

On 2015 Sep 04, Casey M Bergman commented:

Orignally posted at PubPeer: https://pubpeer.com/publications/B37A9BD035CAEA3EEE79C48DDB0378

This paper provides a nice example of natural selection operating on a new gene duplicate at the Resistance to dieldrin (Rdl) locus in in D. melanogaster. Starting with an amino acid variant that is known to confer resistence to the insecticide dieldrin, the authors query whole genome sequences in the Drosophila Genetic Reference Panel (DGRP) [1] and find four strains that contain the resistance mutation. In three of the four strains, the resistance mutation is found unexpectedly in a heterozygous condition. The DGRP strains are highly inbred but are known to contain regions of residual heterozygosity scattered throughout the genome that could arise from incomplete inbreeding or segmental duplication.

By genotyping the offspring of "heterozygous" stocks, the authors find that 100% of progeny retain the heterozygous state, consistent with a segmental duplication. Analysis of the depth of sequence coverage in "heterozygous" strains confirms a 2-fold increase in the depth of coverage for a ~110 kb region containing Rdl and several other genes. The segmental duplication is flanked by two Roo transposable elements, suggesting it arose by ectopic recombination between repetitive sequences. The outcome of the duplication is that one duplicate contains the resitance allele and the other duplicate contains the susceptibility allele. Both copies are expressed. Transgenic analysis confirmed that the cause of the resistence allele is due to a single amino acid change in the Rdl gene only.

This paper shows how a newly arising allele with partial dominance can achieve a state of "permanant heterozygosis" by segmental duplication, conferring immediate adaptive advantage via the new allele while also retaining ancestral function via the old allele. This result nicely confirms a theoretical model developed by Spofford (1969) [2] (not cited in the current work) to explain selective forces that would govern the fixation of a new, polymorphic segmental gene duplicate. This work also shows that the "residual heterozygosity" in the DGRP lines may be more than just background noise from the vagaries of inbreeding, and may in fact point to many other functional segmental duplications in these lines.

[1] Mackay, Trudy FC, et al. "The Drosophila melanogaster genetic reference panel." Nature 482.7384 (2012): 173-178. http://www.nature.com/nature/journal/v482/n7384/full/nature10811.htm

[2] Spofford, Janice B. "Heterosis and the evolution of duplications." American Naturalist (1969): 407-432. http://www.jstor.org/stable/2458991