Sex Chromosome Drive

Sex chromosome drivers are selfish elements that subvert Mendel''s first law of segregation and therefore are overrepresented among the products of meiosis. The sex-biased progeny produced then fuels an extended genetic conflict between the driver and the rest of the genome. Many examples of sex chromosome drive are known, but the occurrence of this phenomenon is probably largely underestimated because of the difficulty to detect it. Remarkably, nearly all sex chromosome drivers are found in two clades, Rodentia and Diptera. Although very little is known about the molecular and cellular mechanisms of drive, epigenetic processes such as chromatin regulation could be involved in many instances. Yet, its evolutionary consequences are far-reaching, from the evolution of mating systems and sex determination to the emergence of new species.Meiotic drivers are selfish genetic elements that subvert Mendelian segregation during gametogenesis for their own benefit. They are passed on to most, if not all, of the functional gametes produced by heterozygotes. Therefore, drivers can increase in frequency and invade populations even if they reduce individual fitness, which is usually the case. The drivers are typically expressed in one sex, of which fertility is impaired. This also has deleterious consequences for the opposite sex and is expected to promote adaptations to counteract drive through sexual selection and sexual conflict. Furthermore, sex-linked meiotic drivers expressed in the heterogametic sex typically lead to biased offspring sex ratios, which represents an additional cost and can exacerbate the sexual conflict.Morgan et al. (1925) were the first to observe sex-biased offspring, which turned out to be caused by a sex-linked meiotic driver. Unfortunately, the Drosophila affinis strain was lost before any conclusive study could be performed. Later, Gershenson (1928) found that the offspring of some Drosophila obscura males were female biased. He showed that these males carried an X-linked genetic element (hereafter “sex ratio” or SR) responsible for the sex-ratio distortion, and showed that the SR did not affect the viability of the male offspring but acted as a gametic killer of Y-bearing sperm. Gamete killing or disabling is observed in males; in females, meiotic drive is usually a result of centromere competition for access to the egg.In its original definition (from Gershenson''s work and others), the term meiotic drive applies to the consequences of the mechanics of the meiotic divisions (Sandler and Novitski 1957). Here, under the term “sex chromosome drive,” we will include more broadly any case of preferential transmission that results directly or indirectly from an event that took place before, during, or after meiosis. Sex chromosome drive is different from sex-ratio adjustment, in which the favored chromosome is not the actor of its drive (West and Sheldon 2002). As emphasized by Sandler and Novitski (1957), it is also different from selection in the haploid phase as a consequence of the gamete''s intrinsic fitness.Only a few dozen cases of sex chromosome drive have been described, mainly in Drosophila and other Diptera (reviewed in Jaenike 2001; Burt and Trivers 2006). One possible explanation for the rarity of reported cases is that a biased sex ratio is not evolutionarily stable. Fisher (1930) predicted that natural selection will favor a 1:1 sex ratio, and that any deviation will be counterselected. This means that variants with counteracting effects can be selected at unlinked loci. Consistent with this prediction, autosomal drive suppressors and resistant Y chromosomes have been found in several Drosophila species (De Carvalho and Klaczko, 1994; Carvalho et al. 1997; Cazemajor et al. 1997). Three different cryptic X-linked SR systems have been described in the same species (Drosophila simulans: Paris, Winters, and Durham systems), showing that they can evolve repeatedly and be completely neutralized in the wild, remaining undetectable unless appropriate genetic crosses are performed (Merçot et al. 1995; Tao et al. 2001, 2007a). D. simulans also teaches us that the time window leading up to neutralization can be very narrow (Bastide et al. 2013). However, variants that enhance distortion can be selected if they are linked to the distorter. Inversions should prevent recombination with nondriving X chromosomes and keep together the loci that interact to induce drive, as found in D. pseudoobscura (Wu and Beckenbach 1983). These examples illustrate the extended genetic conflict that can result from the evolution of sex chromosome drive.Among the known cases of sex chromosome drive, X chromosome drive is much more common than Y chromosome drive. This may be because Y-linked drivers are always expressed, at each generation, unlike X-linked drivers. All else being equal, Y chromosome drive spreads faster and leads to a higher risk of extinction owing to the lack of females (Hamilton 1967). Furthermore, when the sex chromosomes are well differentiated, the Y chromosome usually has many fewer genes, which may provide fewer opportunities for a driver to evolve. On the other hand, heteromorphic sex chromosomes are expected to facilitate the evolution of meiotic drive. Indeed, the more divergent the sex chromosomes are, the less they recombine, reducing the risk of producing a suicide chromosome that carries both the driver and a sensitive allele at the target locus (Charlesworth and Hartl 1978; Frank 1991; Hurst and Pomiankowski 1991).