The magnitude of genetic variation in natural populations is open for debate. Prior to the molecular era that began in the mid-1960s, the magnitude of genetic variation in natural populations remained controversial, with many evolutionary biologists falling into either of two opposing camps: the classicists who maintained that genetic variability in most species was low, such that conspecifics were homozygous for the same “wild-type” allele at most genetic loci; and proponents of the balance view who argued that genetic variation was extensive such that most loci were polymorphic and individuals typically were heterozygous at a substantial fraction of their genes. A central tenet of the classical school was the concept of genetic load: the idea that genetic variation in a population produces a heavy burden of reduced genetic fitness. In support of the classical view was the observation that many de novo mutations are deleterious. In contrast, the balance school tended to view genetic polymorphisms as beneficial and maintained in populations by one or another form of balancing natural selection (such as environmental heterogeneity, heterosis, or frequency-dependent fitness advantage). Two empirical observations sometimes interpreted in favor of the balance view were as follows: phenotypic variation is often extensive in natural populations for many traits; and artificial (human-mediated) selection for various phenotypic attributes was usually successful in many species, thus suggesting that genetic variation must underlie such traits. Nevertheless, by hard criteria such observations were inconclusive for firmly resolving the classical/balance debate. Biologists needed direct information on genetic variation from molecular biology.
population genetic variation; multi-locus protein electrophoresis; molecular markers
The magnitude of genetic variation in natural populations is open for debate. Prior to the molecular era that began in the mid-1960s, the magnitude of genetic variation in natural populations remained controversial, with many evolutionary biologists falling into either of two opposing camps: the classicists who maintained that genetic variability in most species was low, such that conspecifics were homozygous for the same “wild-type” allele at most genetic loci; and proponents of the balance view who argued that genetic variation was extensive such that most loci were polymorphic and individuals typically were heterozygous at a substantial fraction of their genes. A central tenet of the classical school was the concept of genetic load (see Chapter 17): the idea that genetic variation in a population produces a heavy burden of reduced genetic fitness. In support of the classical view was the observation that many de novo mutations are deleterious. In contrast, the balance school tended to view genetic polymorphisms as beneficial and maintained in populations by one or another form of balancing natural selection (such as environmental heterogeneity, heterosis, or frequency-dependent fitness advantage). Two empirical observations sometimes interpreted in favor of the balance view were as follows: phenotypic variation is often extensive in natural populations for many traits; and artificial (human-mediated) selection for various phenotypic attributes was usually successful in many species, thus suggesting that genetic variation must underlie such traits. Nevertheless, by hard criteria such observations were inconclusive for firmly resolving the classical/balance debate. Biologists needed direct information on genetic variation from molecular biology.
Empirically, population genetic variation proved to be unambiguously high. In 1966, three independent research laboratories published the first estimates of genetic variability based on a newly introduced molecular technique: multi-locus protein electrophoresis. The empirical results from these “allozyme” analyses were clear: in organisms as different as humans and fruit flies, individual heterozygosities (the fractions of heterozygous loci) were substantial (often >10%) and a majority of assayed genes displayed molecular polymorphisms.
These findings were so unambiguous that one might suppose they settled the debate soundly in favor of the balance school. However, in an interesting turn of events, the classicists in effect regrouped into what became the neoclassical school of thought or the neutralists (see Chapter 40). The neutralists could not (and did not) deny that molecular genetic variation in most natural populations is extensive, but rather they questioned the degree to which balancing natural selection played an active role in its maintenance. According to the neutralists, most genetic polymorphisms at the molecular level are selectively fitness-neutral.
This breakthrough gets a rather high score for two reasons: overnight, it transformed evolutionary thought about the extensive nature of molecular-level genetic variation; and the protein-electrophoretic technique went on to become the first of many molecular methods that collectively have revolutionized how genetic variation is tapped to provide molecular markers for a wide range of research applications in population ecology, ethology, and evolution.
1. Harris H. Enzyme polymorphism in man. Proc R Soc Lond B. 1966;164:298–310.
2. Johnson FM, Kanapi CG, Richardson RH, Wheeler MR, Stone WS. An analysis of polymorphisms among isozyme loci in dark and light Drosophila ananassae strains from America and Western Samoa. Proc Natl Acad Sci USA. 1966;56:119–125.
3. Lewontin RC, Hubby JL. A molecular approach to the study of genic heterozygosity in natural populations II Amount of variation and degree of heterozygosity in natural populations of Drosophila pseudoobscura. Genetics. 1966;54:595–609.
4. Wallace B. Genetic Load Englewood Cliffs, NJ: Prentice-Hall; 1970.
5. Lewontin RC. The Genetic Basis of Evolutionary Change New York, NY: Columbia University Press; 1974.
6. Avise JC. 1994. Molecular Markers, Natural History, and Evolution. Chapman & Hall, New York, NY [a revised 2nd edition was published in 2004 by Sinauer, Sunderland, MA].