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Theoretical Population Biology 68 (2005) 35 www.elsevier.com/locate/ytpbi

John Maynard Smith and recombination

John Maynard Smith, a leading evolutionary theorist of the second half of the twentieth century, died in April 2004. A major theme of his legacy is the concept of evolutionary stable strategy (ESS) introduced in Maynard Smith and Price (1973) to predict what behavioral traits among a given set can be maintained in a population. It was originally dened in a framework of pairwise contests arising from animal conicts couched in the formalism of game theory. In broad terms, an ESS corresponds to an unbeatable strategy in the terminology of W. Hamilton. The original static concept of ESS has been applied in numerous studies impinging on the evolution of a wide variety of structural and behavioral states including sexuality, altruism, dispersal, recombination, and behavioral covariates. Part of this issue of Theoretical Population Biology is devoted to three individual succinct perspectives by Lessard, Sigmund, and Eshel in memorial to John Maynard Smith focusing mainly on recent developments of the ESS principle and its applications. There is high variability in sex ratio (labeled extraordinary sex ratios by W. Hamilton), variegated sex determination mechanisms and controls, and parental strategies with many population equilibria showing a prominent 1:1 sex ratio, which in the sense of ESS might be considered optimal (see books of Bell, 1982; Charnov, 1982; Karlin and Lessard, 1986). Examples of non 1:1 sex ratio also abound in natural populations inuenced by ecological, environmental, and mating patterns. For example, under an obligatory sib mating population, a pure all female population is anticipated. However, Maynard Smith (1978) established that where females have to compete for local resources and males can move freely, a male biased sex ratio is expected. A population genetic model on the wood lemming on sex ratio was proposed by Bengtsson. Maynard Smith and Stenseth (1978) developed an alternative model based on inbreeding. Apart from ESS theory, Maynard Smith contributed incisively and broadly to many aspects of theoretical population genetics, including analysis of the advantages of recombination events, monomorphism vs. dimorphism, and lately, to topics in genomics, especially relevant to bacterial populations. Maynard Smith was intrigued early with the problem of discerning the evolutionary advantages of sexual recombination. The standard line of reasoning on the advantage of recombination is approximately as follows. Two different advantageous mutations in an asexual population can only be incorporated into a single individual if one of the mutations occurs in a descendant of an individual in which the other mutation occurred. For a sexually reproducing population (i.e., with a recombination mechanism) the two mutations which arise in different individuals can also be combined into the same genome by recombination. However, recombination disrupts associations between mutually favorable advantageous genes while at the same time helping the formation of new advantageous combinations. This balance between recombination producing new types and ultimately breaking up advantageous types has been widely discussed by Dobzhansky, Darlington, Mather, others, and emphasized in Maynard Smith. Crew (1965)in his book on Sex Determination writes: The function of sexual reproduction is to quicken the pace of evolutionary progress by making it possible to obtain an accumulation of advantageous mutational steps without having the respective multiplication of these steps occur in series. Another familiar assertion is that perhaps the optimum strategy for evolution would alternate sexual and asexual phases. Indeed, many organisms encompass in their life cycle both an asexual and a sexual state of different relative durations. Maynard Smith (1968) for a two-locus model of relative tnesses s1 ; s2 s3 , 1, of haplotypes AB, Ab, aB, and ab, respectively, with s1 4s2 41, showed that 2 where the double mutant is more favorable than the independent combinations of single mutants, and if the

doi:10.1016/j.tpb.2005.03.002

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4 S. Karlin / Theoretical Population Biology 68 (2005) 35

initial state is entirely ab individuals, then in subsequent generations the frequency of the double mutant is always larger without recombination than with it (see also Eshel and Feldman (1970). Karlin (1973) studied the foregoing two-locus model for all circumstances of the selection coefcients producing variable conclusions indicating sensitivity of the model in its dependence on initial population composition and inequalities among the selection coefcients. In summary, for the deterministic model with all mutation events favorable recombination is advantageous in accelerating the incorporation of the most favored double mutant provided that the initial population state exhibits negative linkage disequilibrium. The deterministic case is with favorable double mutations but singly deleterious mutants. It is possible for the recombination mechanism to establish a polymorphism and the nature of this equilibrium state is such that the wild type is most abundant while the other haplotypes are represented with positive but small frequency. In a haploid two-locus selection model under the condition where the forms of Ab and aB have tness disadvantage to ab (the wild type) and AB is the most t type, the pure population consisting only of the ab gamete presents a stable state provided recombination is large enough. If unidirectional mutation a ! A; b ! B is introduced into the system, then a mutation selection balance is developed but a sufciently large recombination force is essential for the stability of the polymorphism. The foregoing result testies to the importance of recombination as a mechanism for maintaining potential and actual variability rather than merely for expressing advantages for the efcient incorporation of favored double mutants. It is possible that the notion of the advantage of recombination should be phrased in terms not of the speed of incorporation of mutants but in terms of the variability it permits. In taking account of nite population size in these models, Bodmer (1970) regards the problem of the time until formation of the rst double mutant type as the important criterion by which to gauge the advantage of recombination. Intuitively, if a state exists where the single mutants Ab and aB are present together in the population, the formation of the rst double mutant will be expected earlier if recombination exists as against no recombination. Maynard Smith (1971) emphasized certain ecological factors. He envisages frequent situations where two genetically different populations migrate into a new environment such that the favored genotype is now a mixture of the genes from the invading populations, and sexuality (rather than recombination) will promote the mixing. There are two basic random variables or expectations: (i) the expected time until rst formation of a double mutant labeled F(i) and the expected time

until total xation of AB denoted by E(i) where i i1 ; i2 ; i3 ; i4 indicates the initial state of the population. Concentrating on the initial state w (0, 0, 0, N) such that the population consists initially of the haplotype ab only, we can infer the following contrasting facts: (i) For xed population size N, F(w) is a decreasing function of r (the recombination rate) while (ii) E(w) is an increasing function of r. Thus, in a nite population, without selection effects, increasing recombination is on an average advantageous in speeding the time of rst formation of the double mutant but has the opposite effect of impeding the time of total incorporation. In other words, sex (recombination) is advantageous in speeding the time of rst formation of the double mutant; but it later breaks apart the favored gamete types tending to stretch the xation time beyond that which would be obtained if no recombination mechanism was operating. These assertions are perhaps surprising since in the innite population model where no selection differences operate, recombination exerts no effect on the rate of incorporation. A proper understanding of the role of recombination in the evolutionary process cannot be discussed only in the context of the problem of incorporation of favorable mutations. There is a large literature underlining the importance and effects of recombination for explaining multi-locus equilibria theory, characterizations of modier genes, the nature of polygenic inheritance, the structure of special mating systems, problems related to sex determination and other factors. Obviously, Maynard Smith was highly innovative and simulating in all these matters. References
Bell, G., 1982. The Masterpiece of Nature: The Evolution and Genetics of Sexuality. University of California Press, Berkeley and Los Angeles. Bodmer, W.F., 1970. The evolutionary signicance of recombination in prokaryotes. Symp. Soc. Gen. Microbiol. 20, 279294. Charnov, E.L., 1982. The Theory of Sex Allocation. Princeton University Press, Princeton. Crew, F.A.E., 1965. Sex Determination, fourth ed. Dover, New York. Eshel, I., Feldman, M.W., 1970. On the evolutionary effect of recombination. Theor. Popul. Biol. 1, 88100. Karlin, S., 1973. Sex and innity: a mathematical analysis of the advantages and disadvantages of genetic recombination. In: Bartlett, M.S., Hiorns, R.W. (Eds.), The Mathematical Theory of the Dynamics of Biological Populations. Academic Press, London, pp. 155194. Karlin, S., Lessard, S., 1986. Theoretical Studies on Sex Ratio Evolution. Princeton University Press, Princeton. Maynard Smith, J., 1968. Evolution in sexual and asexual populations. Am. Nat. 102, 469473. Maynard Smith, J., 1971. What use is sex? J. Theor. Biol. 30, 319335. Maynard Smith, J., 1978. The Evolution of Sex. Cambridge University Press, Cambridge.

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S. Karlin / Theoretical Population Biology 68 (2005) 35 Maynard Smith, J., Price, G.R., 1973. The logic of animal conict. Nature 246, 1518. Maynard Smith, J., Stenseth, N.C., 1978. On the evolutionary stability of the female-biased sex ratio in the wood lemming (Myopus schisticolor): The effect of inbreeding. Heredity 41, 205214. 5

Samuel Karlin Department of Mathematics, Stanford University, Stanford, CA 94305-2125, USA E-mail address: karlin@math.stanford.edu 24 March 2005