Adaptation by natural selection proceeds most efficiently when alleles compete solely on the basis of their effects on the survival and reproduction of their carriers. A major condition for this is equal Mendelian segregation, but meiotic drive can short-circuit this process. The evolution of drive often involves multiple, interacting genetic components, together with enhancers and suppressors of drive. Chromosomal inversions that suppress crossing over are also frequently associated with drive systems. This study investigates the effects of these processes on patterns of molecular evolution in the fly Drosophila recens, which is polymorphic for a driving X chromosome (X D ). Whereas standard wild-type chromosomes exhibit high levels of polymorphism at multiple loci, all of the X D chromosomes effectively carry a single multilocus haplotype that spans at least 130 cM. The X D is associated with a complex set of inversions that completely suppresses recombination between the standard wild-type chromosome and X D in heterozygous females, which maintain nonrandom associations among loci that presumably interact epistatically for the expression of drive. The long-term costs of foregoing recombination may be substantial; in combination with its low equilibrium frequency, this makes the X D chromosome susceptible to the accumulation of deleterious mutations. Consistent with this, X D chromosomes are apparently fixed for a recessive mutation that causes female sterility. Thus, the X D in D. recens appears to be in chromosome-wide linkage disequilibrium and in the early stages of mutational degradation.Drosophila recens ͉ genetic conflict ͉ inversion ͉ population genetics ͉ segregation distortion M endelian segregation ensures that alleles compete on a level playing field, thus maximizing the efficiency of natural selection (1). Although the deterministic spread of an allele under selection is generally thought to occur because of a fitness benefit to its carriers, this can also come about as a result of biased transmission through mechanisms such as meiotic drive (2). By being transmitted to more than half of the gametes, driving alleles can spread even if they adversely affect the fitness of their carriers. Furthermore, when such alleles occur on the X or Y chromosome, this can result in an unequal population sex ratio, further penalizing individuals that produce an excess of the more abundant sex (3). This can even lead to population extinction if the driver reaches a sufficiently high frequency (4).Drive systems involve multiple, interacting components, usually with both enhancers and suppressors of drive (2). Epistatic interactions among these components favor suppression of crossing over among them (5). Close linkage among the core components of drive systems may be required for their initial evolution, because otherwise low-fitness genotypes are produced by recombination (6). It is therefore not surprising that drive loci are often found in low recombination regions, such as heterochromatin, and/or are associated...