Heredity (2009) 103, 445–457 & 2009 Macmillan Publishers Limited All rights reserved 0018-067X/09 $32.00 www.nature.com/hdy REVIEW A combinational theory for maintenance of sex EHo¨randl Department of Systematic and Evolutionary Botany, Faculty of Life Sciences, University of Vienna, Vienna, Austria Sexual reproduction implies high costs, but it is difficult to give prolonged growth periods. For complex multicellular organ- evidence for evolutionary advantages that would explain the isms, the main advantage of sexuality is thus the alternation of predominance of meiotic sex in eukaryotes. A combinational diploid and haploid stages, combining advantages of both. theory discussing evolution, maintenance and loss of sex may A loss of sex is constrained by several, partly group-specific, resolve the problem. The main function of sex is the restoration developmental features. Hybridization may trigger shifts from of DNA and consequently a higher quality of offspring. sexual to asexual reproduction, but crossing barriers of the Recombination at meiosis evolved, perhaps, as a repair parental sexual species limit this process. For the concerted mechanism of DNA strand damages. This mechanism is most break-up of meiosis-outcrossing cycles plus silencing of efficient for DNA restoration in multicellular eukaryotes, secondary features, various group-specific changes in the because the initial cell starts with a re-optimized genome, regulatory system may be required. An establishment of which is passed to all the daughter cells. Meiosis acts also asexuals requires special functional modifications and envir- as creator of variation in haploid stages, in which selection onmental opportunities. Costs for maintenance of meiotic sex can purge most efficiently deleterious mutations. A prolonged are consequently lower than a shift to asexual reproduction. diploid phase buffers the effects of deleterious recessive Heredity (2009) 103, 445–457; doi:10.1038/hdy.2009.85; alleles as well as epigenetic defects and is thus optimal for published online 22 July 2009 Keywords: sex; apomixis; evolution; polyploidy; meiosis The paradox of sex ubiquitous feature of eukaryotic sex. In hermaphroditic organisms, costs of males are reduced to that of a male Why do most eukaryotic organisms reproduce sexually? function, but have still been estimated as being around The evolution of sex has been considered the ‘Queen’ of 1.5-fold (Lloyd, 1988). A more comprehensive inventory evolutionary biology (Williams, 1975; Bell, 1982) and is over all groups of organisms showed five potential costs still under intensive debate. Sex is understood here in a of sex (Lewis, 1987): (1) cellular–mechanical costs of broad sense as ‘a process in which the genomes of two meiosis and syngamy (the time needed for meiosis, parents are brought together in a common cytoplasm to syngamy and karyogamy, which confers an inactive stage produce progeny, which may then contain re-assorted and a delay of synthetic processes); (2) recombination portions of the parental genome’ (Bernstein et al., 1984; (breakup of favourable combinations of alleles); (3) Birdsell and Wills, 2003). In a broad definition, sex occurs fertilization (risk exposure and density dependence); (4) in viruses, prokaryotes and eukaryotes. In prokaryotes, cost of males and ‘genome dilution’ sensu Lewis, 1987 (a sex is not directly linked to reproduction, which is sexual parent transmits only 50% of its genes to the understood here as a process of forming new indivi- offspring); and (5) costs of sexual selection. Whereas (1) duals. In eukaryotes, sex is predominantly directly and (2) are costs of meiosis, (3)–(5) are costs of out- linked to reproduction in the combined processes of crossing; a discussion of costs of sex in this sense restricts meiosis and outcrossing. the topic to sex of eukaryotic organisms. The paradox of maintenance of sex in eukaryotes arises Short-term advantages of asexuality are manifested in from the fact that it has a lot of immediate individual the taxonomically widespread phenomenon that asexual costs, whereas it is difficult to give evidence for any animals and plants often have much larger distribution advantages compared with asexual reproduction. The areas than their sexual relatives, and tend to higher basic assumption suggests two costs of sex: the cost of altitudes and latitudes and previously glaciated areas meiosis (which breaks up co-adapted gene combinations) (Kearney, 2005; Ho¨randl, 2006, 2009; Ho¨randl et al., 2008). and that of male individuals not producing offspring Such observations suggest a higher general fitness for (Maynard Smith, 1978; Bell, 1982). The latter point is asexual reproduction. Nevertheless, this phenomenon is strongly orientated towards sex in bisexual organisms, for restricted to a few genera and certain geographical areas, example most animals. Gender separation, however, is no where environmental changes may have provided opportunities for shifts to asexuality (Ho¨randl, 2009). The taxonomic distribution of meiotic sex, however, is Correspondence: Dr E Ho¨randl, Department of Systematic and Evolu- predominant among all groups of eukaryotes and not tionary Botany, Faculty of Life Sciences, University of Vienna, Rennweg restricted to certain environmental conditions. 14, 1030 Vienna, Austria. E-mail: [email protected] A large number of theories have been developed for Received 2 April 2009; accepted 3 May 2009; published online 22 the long-term success and maintenance of sexuality, but July 2009 none of them have provided unequivocal support for a Paradox of sex EHo¨randl 446 single hypothesis. In general, hypotheses for the main- meiosis need of a DNA repair mechanism tenance of sex can be grouped into three main categories in g (Birdsell and Wills, 2003): (1) sex as an effective way second chromosome template to create genetic variation in the offspring, which allows outcrossing (mixis) needed for recombination for a faster adaptation to environmental variability oxidative damage; problem of repair (for example, Burt, 2000); these models rely mostly on multicellularity of nuclear DNA for somatic cells the effects of recombination. (2) Sex as a restoration mechanism for damage of DNA strands, or mutational or restoration of nuclear selection for offspring with repaired nuclear DNA epimutational change of the genome; here the main DNA in the initial cell arguments are that meiosis would provide a tool for selection on mutations in haploid maintenance ori repair of double-strand breaks (for example, Bernstein diploid-haploid cycles phases; evolution of complex organisms (see Fig. 2) et al., 1988; Bernstein, 1998) or would restore DNA secondary features, methylation patterns (for example, Holliday, 1988). constraint of meiosis and mating crossing barriers compatibility; balance of costs of Recombination would also avoid a long-term accumula- outcrossing tion of disadvantageous mutations; an asexual lineage phylogenetic fixation inheritance of complex sexual cannot produce offspring with a lower mutational load systems from the ancestor than any previous generation (Muller’s ratchet). More- over, recombination can break up negative epistasis and predominance of sexual multiple costs of shifts to asexuality thus allows for a more efficient purging of deleterious reproduction in complex organisms; no constraint constraints of loss mutations (Kondrashov, 1988, 1993). (3) A third group of for sexual speciation hypotheses regards sex as a consequence of phylogenetic Figure 1 Hypothetical outline of evolutionary history of sexual fixation, that is, a feature inherited from ancestors that reproduction in eukaryotes. Steps towards obligate sexual repro- we cannot get rid of. This model does not seek an duction (left column). Functional constraints and selective forces advantage of sexual reproduction per se, but regards it as driving evolution from one step to the next (right column). a ‘imperative relic’ inherited from eukaryotic ancestry (Margulis and Sagan, 1986). It exceeds the topic of this paper to review all previous hypotheses. The compre- restoration phase haploid phase hensive review by Birdsell and Wills (2003) outlines pros purging selection against recessive deleterious mutations and cons of all contemporary models. In general, it is minimal cell differentation difficult to give evidence for ubiquitous advantages of meiosis zygote single factors that would compensate the costs of sex. recombination: Therefore, many modern authors argue for pluralistic physical DNA repair combines two “re-optimized” genomes approaches and combinations of mutation- and recom- epigenetic repair (passed to all daughter cells) bination-based models (West et al., 1999; Pound et al., 2004; Ben-Ami and Heller, 2005; Cooper et al., 2005). reproductive cells Empirical data from extant asexual organisms draw diploid phase attention to some hitherto overlooked factors, such as the somatic cells growth and cell differentiation importance of shifts of ploidy levels. In this study, I wish oxidative damage buffering of deleterious mutations duration phase to integrate these factors into new theory, which and epigenetic damage combines previous ideas in a framework of evolutionary death history and increasing complexity of organisms. Origin, Figure 2 Scheme of potential advantages of sex in complex maintenance and constraints of loss of sex have different multicellular organisms. A haploid restoration phase of the genome reasons and selective forces (Figure 1). Meiosis-out- alternates with