Applying and extending the notion of genetic linkage: the first fifty years
Four major ideas have shaped modern genetic research: Mendel’s conception of inheritance of discrete Faktoren, Johannsen’s distinction between genotype and phenotype, Morgan’s notion of genetic linkage, and Watson and Crick’s model of DNA structure. In this chapter I deal with the third, less acknowledged, of these major epistemic breakthroughs: the interpretation of deviations from independent segregation of Mendelian factors as function of the location of genes along chromosomes. Contrary to Mendel’s law of independent inheritance of Faktoren, correlated inheritance of traits was time and again observed. However, in the early days of Mendelism there was no clear distinction between multiple effects of the same factor and multiple factors each with a different effect. I propose that the notion of genetic linkage was conceived in the context of resolving such correlation between inherited traits by discriminating those due to the mechanics of inheritance of discrete genes from those due to multiple physiological effects of specific genes. Although linkage maps were only devices that presented results of genetic experiments they were believed to be at least collinear with the structures of the material chromosomes. In this sense, they were hypothetical constructs (MacCorquodale and Meehl 1948) or virtual maps of the chromosomes. But once established, linkage became a central methodological tool of genetic analysis. Here I examine how the virtual maps constructed from linkage data provided the instruments for the establishment of the chromosome theory of inheritance and of chromosomal mechanics as a hypothetical construct. Furthermore, I contend that linkage became also an experimental device for the examination of the integration of genetic functions in development and evolution. These include notions
such as “position effect” changes of phenotypes, cordoned-off blocks of evolutionary co-adapted genes, or inadvertent sweepings of neighboring genes causing “linkage disequilibrium.” With the transition of classical to molecular genetics new tools and methods were developed, but to a large extent many of the new concepts were elaborated on the background of established genetic concepts. The examination of homologies between organisms by in vitro hybrids of their DNA molecules, the location of genes on DNA restriction maps or by DNA walking are basically modern extensions of the notion of genetic linkage.