92 James F. Crow
of Heredity on coat color inheritance in mammals[Wright, 1917-1918]. These
included rats, guinea pigs, mice, cattle, horses, swine, dogs, cats, and humans.
This early analysis was remarkable in two ways. One was his finding similarities
and presumed homologies among genes with similar effects in these species; many
have since been confirmed. The second is his interpretation of these colors in terms
of the latest knowledge of enzymes and pigment chemistry. As often, he was ahead
of his time.
Wright’s approach was always quantitative. An early paper analyzed the inher-
itance of size factors into components, based on correlation of various body parts.
He was able to subdivide the variance of size into components of (1) general size,
(2) limb-specific factors, (3) fore- and hindlimb factors, (4) upper- and lower-limb
factors, and (5) special factors for each part[Wright, 1918]. This was the forerun-
ner of several papers by various authors, who did similar analyses in a number of
species.
Wright’s deepest interest was in the interaction of genes affecting coat color
in guinea pigs. He formulated the relationship in path diagrams assuming flux
equilibrium and expressed the various chemical processes as differential equations.
His papers showed his mastery of the latest concepts of enzyme chemistry. Wright’s
major analysis of this kind was presented in 1941[Wright, 1941]. He had plans
for a book on this subject. But 1941 was the year that biochemical mutants
in Neurospora were discovered, and this opened up the opportunity for a much
more direct attack on gene-enzyme relations. I think Wright realized that this
represented a new direction in genetics, as indeed it did, for it led to the discovery
of sex in bacteria and ultimately to molecular genetics and the nature of the gene.
Wright continued to do guinea pig studies, with increasingly elaborate analyses of
the action and interaction of the various genes. These studies were masterful, but
their great detail made them difficult to read. In fact they attracted very little
attention. The fashion had changed and Wright’s kind of analysis was replaced by
molecular biology and direct chemical analysis.
One point should be mentioned. Wright was often impressed by the frequent
unpredictability of interactions. Often the combined effect of two genes was not
at all like what would be expected from their individual effects. Such examples
had a large effect on Wright’s thinking, especially his shifting balance theory of
evolution.
5 POPULATION GENETICSAs mentioned earlier, population genetics was founded and almost completely
dominated for a number of years by Haldane, Fisher, and Wright. Their styles were
quite distinctive. Haldane wrote a series of papers that systematically explored
selection under a wide variety of circumstance. These were mainly single locus
models and the mathematics was relatively simple, summarized in[Haldane, 1932].
Haldane is also responsible for the concept of “mutation load”, the idea that the
impact of mutation on the population is determined mainly by the mutation rate