 This issue was central to Cyril Darlington’s analysis in his 1939 book The Evolution of Genetic Systems (Darlington 1939). Darlington noted that the organization of the karyotype, or the “genetic system” to use his terminology, and its dynamics throughout the mating group, affect the hereditary combinations that are produced, and hence hereditary variation, and can lead to reproductive isolation and speciation. The following quote gives the general flavor of Darlington’s line of thought,