One method of speciation is reproductive isolation.  One model for this is the Bateson–Dobzhansky–Muller model, where if a species is, say, separated by distance, and then subgroup A has a change at one loci, and subgroup B has a change at another loci, and due to these mutations, individuals from subgroup A can no longer reproduce with individuals fom subgroup B - then it can be said that speciation from reproductive isolation has occurred according to this model.