The Gene Pool; Equilibrium Factors 



209 



The second type of heterotic effect can 

 be illustrated in human beings. As men- 

 tioned on p. 71, homozygotes for the gene 

 for sickle cell anemia (/3 B [J a ) usually die 

 from anemia before adolescence. f} A {l A in- 

 dividuals have normal blood type, whereas 

 ff A fj a individuals are either normal or have 

 a slight anemia. In certain countries the 

 frequency of /3 s in the gene pool follows the 

 expectation for a recessive lethal gene. In 

 other countries, however, fj s is more fre- 

 quent than expected. This difference is at- 

 tributable to the (3 A f3 s heterozygote being 

 more resistant to certain kinds of malaria 

 than the f3 A f3 A homozygote. Of course, in 

 nonmalarial countries, (3 s confers no anti- 

 malarial advantage, and so the fitness of the 

 heterozygote (1 — s) is lower than that of 

 the normal homozygote ( 1 ) , whereas the 

 ,3' s 7? 8 individual has a fitness of zero. As 

 expected, therefore, sickle cell anemia is rare 

 or absent in most of the world where certain 

 forms of malaria are absent. 



On the other hand, in certain malarial 

 countries, even though heterozygotes may be 

 slightly anemic, the advantage of being re- 

 sistant to malaria produces a greater overall 

 fitness than does the (3 A /3 A genotype. Here 

 the fitness of the heterozygote, f3 A (3 s , is 

 maximal and therefore must be assigned the 

 value one, whereas that of the normal homo- 

 zygote, f3 A p A , is one minus Si. Mutant 

 homozygotes, /? >s '/?' s ', have a fitness of one 

 minus s 2 , where s 2 equals one, since all f3 s (3 s 

 die (even if extremely resistant to malaria). 

 In this situation natural selection maintains 

 both fi A and /3 s in the gene pool, (3 s having 



a frequency equal to 



This fraction 



Si + s 2 



can be read as "the advantage of f3 s (as 

 shown by the advantage of fl A (3 s over /3 A f3 A ) 

 divided by the total disadvantage of f3 A and 

 /3 s ." Thus, when the heterozygote, being 

 more adaptive than either homozygote, 

 shows heterosis in this way, natural selection 



maintains a gene such as (1* in the gene pool 

 even though it is lethal when homozygous. 



Although we have discussed heterosis in 

 terms of the phenotypic effects of the mem- 

 bers of a pair of alleles, it should not be in- 

 ferred that the unit of heterotic action is 

 always a single pair of genes. Since we 

 know that different pairs of genes interact 

 in various ways to produce phenotypes, it 

 would not be surprising to find that heterosis 

 results from the effects of combinations of 

 nonalleles and alleles. 



Natural populations of Drosophila pseudo- 

 obscura contain various paracentric inver- 

 sions. Laboratory populations can be 

 started with some individuals carrying the 

 normal chromosome arrangement and others, 

 a particular one of these inversions. After 

 a number of generations has passed, in some 

 cases the population comes to contain only 

 normal chromosomes, because the inversion 

 chromosome behaves like a detrimental gene 

 which provides no advantage when hetero- 

 zygous and is eliminated from the gene pool. 

 When other particular inversions are tested 

 this way, however, an equilibrium is reached 

 — both the normal and inverted chromo- 

 somes are retained in the gene pool. In 

 these cases, the inversion heterozygote is 

 adaptively superior to either homozygote, 

 showing heterosis just as the gene for sickling 

 in malarial countries. It is difficult to decide 

 the genetic basis for heterosis in such cases, 

 however, since the hybrid vigor could be 

 due to: the genes gained or lost at the time 

 the inversion was initially produced; or the 

 new arrangement of the inverted genes; or 

 the types of genes or groups of genes con- 

 tained within the inversion. Recall that in- 

 dividuals with paracentric inversions are not 

 at a reproductive disadvantage in Drosophila 

 and suppose a heterotic system exists or de- 

 velops in Drosophila heterozygous for a 

 paracentric inversion. If the heterosis is due 

 to the action of several specific nonalleles 



