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This page describes the Dobzhansky-Muller model and I can follow the illustration of the split leading to incompatible hybrids.

But at the start of the page the author states "[Dobzhansky and Muller] both realized that hybrid inviability or sterility was unlikely to arise from a single change at one locus." I don't really understand the explanation that follows i.e. what exactly is the issue with having a single change at one locus?

I wonder if someone here could explain the issue more clearly.

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If reproductive isolation was to be caused by a single mutation, then the first individual to carry this mutation would likely have a very low fitness. At the extreme, in a purely sexually reproducing species without hermaprohiditism, this individual carrying the first mutation causing reproductive isolation would have no-one to reproduce with and would have a fitness of zero.

Hence, reproductive isolation is unlikely to arise from a single mutation as these mutations are unlikely to raise into appreciable frequency. Hence, Dobzhansky and Muller (and Bateson) created this minimalist model involving only two loci with negative epistatic interactions.

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