Genetic Polymorphism
E. B. Ford, 1965

The Polymorphism Concept

85 It would be useless to add a summary to this Monograph for it contains much which requires detailed explanation, together with a number of deductions that are new. Such things become distorted or incomprehensible if compressed. I am therefore ending this survey with a few general propositions involved in the polymorphism concept.

Science sometimes proceeds by way of definitions and their absence may impede its advance, for it may become possible to analyse some aspect of a complex system merely because it has been defined. So it was when a component of the variation occurring in living organisms was distinguished as a genetic polymorphism. For this proved to be a distinct form of diversity, recognizable and endowed with predictable properties. These, for the present purpose, are three in number: (1) the phases, which are necessarily discontinuous, are relatively common (pp. 11, 14) compared with those maintained merely by mutation. (2) Polymorphism promotes the evolution of super-genes. (3) It is essentially associated with selection, often of a powerful kind.

Whenever the environment so changes that a rare major gene begins to spread, it will almost invariably evolve into a polymorphism, maintained by contending advantages and disadvantages. Thus polymorphic phases must be extremely common and, unless they are in process of taking up their equilibria (transient polymorphism), they will be poised at neutrality by opposed selective forces. Both for this reason, and on account of the high relative frequency even of the rarer alleles controlling them, they are capable of rapid evolution, including dominance-modification, and of sensitive adjustment to new conditions. 86 Therefore polymorphism was picked upon early in the study of ecological genetics as providing one of the three situations in which evolutionary change proceeds fast enough to be detected and analysed by observation and experiment. It was on this account also that, contrary to the then accepted view, the human blood groups were recognized as selectively important and associated with liability to specific diseases.

Moreover, the relatively high frequency of all the phases in polymorphism should make it possible to locate a number of useful marker-genes on each of the human chromosomes. A chromosome map of Man, far less detailed than that already obtained for some other organisms, would be of much assistance in predicting the segregation of hereditary diseases and abnormalities in families in which they occur.

It has been explained that the switch-control in polymorphism must tend to evolve into a super-gene (pp. 18-21). A detailed experimental and cytological study of that process should rank as a high priority in the analysis of evolutionary mechanisms. Moreover, its relative rapidity in polymorphism should prove an invaluable guide to the mechanism by which it is incorporated into the evolution of adaptations in general, so as to prevent the scatter from one another of co-adapted genes owing to segregation and crossing-over.

Polymorphism must often be cryptic; so much so that, difficult to detect as the condition then becomes, it has even in that state already been recognized in a wide range of instances, of which the human blood groups are the most celebrated. We may suppose that any external effects of genes and super-genes controlling important physiological qualities will frequently have been obliterated by selection except in situations or environments to which the organism is not normally exposed. These therefore may uncover hidden diversity.

For example, Kettlewell (1944) bred Panaxia dominula (Arctiidae) from typical parents found at Deal, Kent. He divided the brood into two batches, one was raised in normal conditions with the usual varying temperatures. It produced 20 imagines, all ordinary dominula like the parents. 87 The second batch was reared at a constant temperature of 70 +/- 5 deg. F. It gave rise to 23 adults, comprising 6 normal dominula, 5 homozygotes representing an extreme variety [bimacula] in which nearly all the white spotting on the fore-wings was obliterated while there was an excess of black markings on the hind pair, and 12 intermediate heterozygotes [medionigra]. The latter were the most variable group and were nearer the mutant than the normal homozygotes in appearance. That is to say, the effect of a gene to which the species seems buffered in natural conditions had been uncovered when the larvae were reared at a constant temperature; an environment which, of course, the moth never experiences.

In this instance we may be dealing with a rare mutant, not a polymorphism. It would be important to rear animals and breed plants from wild stocks exposing them, with adequate controls, to abnormal conditions of various kinds and to detect and study any cryptic polymorphisms which might then become apparent.

There is indeed abundant evidence for the existence of that condition in a wide range of species (Ford, 1964, p. 90). It may be exemplified by means of the human dimorphism already mentioned (pp. 81-2) with its rarer phase comprising 20 to 30 per cent of the population in Europe and the Middle East, which is detectable only with respect to the taste of phenyl-thio-urea: a compound quite outside ordinary experience, one that had not even been synthesized until this century. The variation involved is therefore cryptic, though we can deduce that it has important effects; indeed some hint of its influence upon the thyroid gland has already been obtained.

Many cryptic human polymorphisms are likely to be of physiological significance, such as rapid and slow inactivation of isoniazid (see Clarke, 1964, pp. 257-61), while all of them are of relevance to medical studies. We may hope to discover some of them by means of unusual scent and taste stimuli. It has long been known that various plant species produce flowers which appear strongly scented to some people but scentless to others, all of whom have in general an equally good sense of smell (Blakeslee, 1918). As in many of these instances, the capacity to detect the scent of freesias (Blakeslee, 1932) is polymorphic; it is at present being studied intensively by K. G. McWhirter. 88 But a wide range of cryptic polymorphism in Man might be uncovered by testing extensively for such sensory discrimination by means of chemicals and the scents both of flowers and of Lepidoptera: some of the latter are clearly distinguishable to certain people.

Cryptic polymorphism in other animals and in plants may be revealed not only by placing them in an unusual external environment but by studying individuals possessing an exceptional gene-complex, especially when arising from the hybridization of distinct races or species. The detection both of such phases, and of those that are phenotypically evident in normal circumstances, is of much importance in the experimental study of evolution. For the existence of a polymorphism is a sure sign of evolutionary change if it be transient, and of the action of contending selective forces if it be of the normal balanced form. That such selection is likely to be powerful, promoting sensitive adjustments to changing conditions, is a fair deduction from recent research on ecological genetics.