Comparative studies have not played a central role in the development of mammalian genetics until quite recently. The reason for this is clear: There was little to compare with ease and certainty until spectacular advances in molecular biology revealed details of the genetic structure of many mammalian species. Coat color was the one major exception before the advent of molecular technologies. In the early decades of the century, much information accumulated on the genetics of coat colors in a wide array of mammalian species, and a few pioneers in genetics, including some of the outstanding figures in the history of the discipline, used this knowledge to speculate on the comparative aspects of mammalian genomes.

J. B. S. Haldane emerged as the dominant figure in this endeavor. In 1927, he published a famous paper in which he discussed the fundamentals of homology and how these could be demonstrated by examining the coat color genetics of six species of rodents and nine species of carnivores (Haldane 1927). His criteria for homology are presented, together with those of Lalley and McKusick (1985), in Table 1. Although the language and details understandably differ, the agreement on the fundamentals necessary for making a decision is impressive. Despite advances that have made the assignment of homology much more reliable, the uncertainty inherent in Haldane's criteria persists.

Haldane and others, notably Little (1958) and Searle (1961, 1968, 1969), recognized that the closer the phenotypes were to the primary action of the genes in question, the stronger any decision on homology would be.