Bottlenecks, genetic polymorphism and speciation.

THIRTY years ago Takeo Maruyama, Ranajit Chakradominant selection can be much greater than that mainborty, and I published an article about the effects tained by mutation-selection balance, but that overdomof bottlenecks on genetic variation (Nei et al. 1975). This inant selection incurs a large genetic load (genetic death article was motivated by two controversies occurring in or fertility excess required) that may not be bearable by evolutionary genetics at that time. One was the selecmammalian organisms when the number of loci is large tionist-neutralist controversy concerning the mainte(Kimura and Crow 1964). For this reason, Lewontin nance of protein polymorphism, and the other was the and Hubby (1966) could not decide between the two controversy over Mayr’s (1963) and Carson’s (1971) hypotheses when they found electrophoretic variation. idea that speciation is caused by the genetic revolution However, Sved et al. (1967), King (1967), and Milkman that occurs when population size is drastically reduced (1967) proposed that this genetic load can be reduced by bottleneck effects. I do not think that we resolved substantially if natural selection occurs by choosing only any of these controversies to everyone’s satisfaction, but individuals in which the number of heterozygous loci we clarified several aspects of the bottleneck effects in is greater than a certain number (truncation selection). evolutionary genetics. Soon after these articles were published, Crow (1970) The first controversy was initiated when protein elecand Nei (1971) argued that, unlike artificial selection, trophoresis revealed a large amount of genetic variation natural selection does not involve truncation selection. in natural populations (Shaw 1965; Harris 1966; LewIn the meantime, Robertson (1967), Crow (1968), ontin and Hubby 1966). Historically, this controversy and Kimura (1968) suggested that most protein polywas a new version of the previous controversy concernmorphisms are probably neutral and that the wild-type ing the maintenance of genetic variation. In the 1950s, alleles in the “classical” hypothesis are actually compopulation geneticists were divided into two camps, one posed of many iso-alleles or neutral alleles. camp supporting the “classical” theory and the other the However, the “balance” camp did not accept this sug“balance” theory (Dobzhansky 1955). The “classical” gestion, because they believed that almost all genetic theory asserted that most genetic variation within species polymorphisms were maintained by balancing selection is maintained by mutation-selection balance, whereas the (Clarke 1971). At that time, surveying the average het“balance” theory proposed that genetic variation is mainerozygosity (H ) for a number of species, Lewontin tained primarily by overdominant selection or some (1974, p. 208) and Ohta (1974) noted that H was 6– other type of balancing selection. The major supporters 18% for most species, irrespective of its population size. of the “classical” theory were H. J. Muller, James Crow, If the neutral theory were correct, H should increase and Motoo Kimura, and those supporting the “balance” with increasing population size (N). Therefore, Lewontheory were Theodosius Dobzhansky, Bruce Wallace, tin and Ohta took this observation as evidence against and E. B. Ford. During this controversy, it became clear the neutral theory. Ayala (1972) estimated that the that the amount of genetic variation maintained by overeffective population size of Drosophila willistoni in South America is at least 109 so that the expected heterozygosity would be 0.976 if the mutation rate is 10 7/locus/ This article is dedicated to the memory of Takeo Maruyama. year or 10 8/locus/generation. Under the neutral the1Address for correspondence: Institute of Molecular and Evolutionary ory, the expected heterozygosity in an equibrium popuGenetics, 328 Mueller Lab, Pennsylvania State Unversity, University Park, PA 16801. E-mail: [email protected] lation is given by 4Nv/(4Nv 1), where v is the muta-