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Meiotic drivers are genetic variants that selfishly manipulate the production of gametes to increase their own rate of transmission, often to the detriment of the rest of the genome and the individual that carries them. This genomic conflict potentially occurs whenever a diploid organism produces a haploid stage, and can have profound evolutionary impacts on gametogenesis, fertility, individual behaviour, mating system, population survival, and reproductive isolation. Multiple research teams are developing artificial drive systems for pest control, utilising the transmission advantage of drive to alter or exterminate target species. Here, we review current knowledge of how natural drive systems function, how drivers spread through natural populations, and the factors that limit their invasion. Trends Box  Both naturally occurring and synthetic "meiotic drivers" violate Mendel's law of equal segregation and can rapidly spread through populations even when they reduce the fitness of individuals carrying them. Synthetic drivers are being developed to spread desirable genes in natural populations of target species. How ecology influences the population dynamics of meiotic drivers is important for predicting the success of synthetic drive elements. An enduring puzzle concerns why some meiotic drivers persist at stable, intermediate frequencies rather than sweeping to fixation. Drivers can have a wide range of consequences from extinction to changes in mating system. preferentially associating with and moving toward the egg pole at Meiosis I) will be 75 transmitted to more than half of the maturing eggs. Although this bias does not necessarily 76 reduce the production of eggs (as only one egg matures per meiosis), the fitness of other 77 alleles at the same locus, that do not bias transmission, and alleles linked to them, is 78 reduced. Such meiotic drivers could reduce the fitness of individuals that carry them, if the 79 driving variant is genetically linked to deleterious mutations or has deleterious pleiotropic 80 effects. 81Male meiotic drive takes multiple forms -some at least partially meiotic, some entirely 82 post-meiotic -but all involve a driving element that prevents maturation or function of 83 sperm that do not contain it. Because haploid sperm within a single ejaculate compete to 84 fertilize the same pool of eggs, disabling non-carrier sperm results in transmission of the 85 driving element to more than half of the functional gametes and resulting offspring ([5], Box 86 1). However, disabling non-carrier sperm often reduces fertility [6]. 87Spore drive in fungi, in which the products of meiosis are packaged together in an ascus, 88 operates via similar mechanisms. Spores with one haploid genotype will kill or disable 89 spores of the alternative haplotype ([7], Box 1). If spores disperse long distances sibling 90 spores are unlikely to compete and killing them will not increase the killer's fitness. 91However, spore killing can be beneficial if there is local resource competition. 92Excit...

Segregation Distorter (SD) is an autosomal meiotic drive gene complex found worldwide in natural populations of Drosophila melanogaster. During spermatogenesis, SD induces dysfunction of SD + spermatids so that SD/SD + males sire almost exclusively SD-bearing progeny rather than the expected 1:1 Mendelian ratio. SD is thus evolutionarily "selfish," enhancing its own transmission at the expense of its bearers. Here we review the molecular and evolutionary genetics of SD. Genetic analyses show that the SD is a multilocus gene complex involving two key loci-the driver, Segregation distorter (Sd), and the target of drive, Responder (Rsp)-and at least three upward modifiers of distortion. Molecular analyses show that Sd encodes a truncated duplication of the gene RanGAP, whereas Rsp is a large pericentromeric block of satellite DNA. The Sd-RanGAP protein is enzymatically wild type but mislocalized within cells and, for reasons that remain unclear, appears to disrupt the histone-to-protamine transition in drive-sensitive spermatids bearing many Rsp satellite repeats but not drive-insensitive spermatids bearing few or no Rsp satellite repeats. Evolutionary analyses show that the Sd-RanGAP duplication arose recently within the D. melanogaster lineage, exploiting the preexisting and considerably older Rsp satellite locus. Once established, the SD haplotype collected enhancers of distortion and suppressors of recombination. Further dissection of the molecular genetic and cellular basis of SD-mediated distortion seems likely to provide insights into several important areas currently understudied, including the genetic control of spermatogenesis, the maintenance and evolution of satellite DNAs, the possible roles of small interfering RNAs in the germline, and the molecular population genetics of the interaction of genetic linkage and natural selection.Mendelian inheritance is a marvelous device for making evolution by natural selection an efficient process.... The Mendelian system works with maximum efficiency only if it is scrupulously fair to all genes. It is in constant danger, however, of being upset by genes that subvert the meiotic process to their own advantage. James F. Crow (1979) S EGREGATION Distorter (SD) is a selfish, coadapted gene complex on chromosome 2 (an autosome) found at low frequency in nearly all natural populations of the fruit fly, Drosophila melanogaster. In heterozygous males carrying SD and a typical wild-type second chromosome (SD/SD + ), most SD + -bearing spermatid nuclei fail to complete the histoneto-protamine transition during spermiogenesis, so that primarily SD-bearing spermatids develop properly and go on to fertilize eggs. SD/SD + males thus sire almost exclusively SD-inheriting progeny. This distortion of classic Mendelian ratios has intrigued geneticists and evolutionary biologists for more than 50 years-and for good reason. As we describe below, SD is a newly evolved system that subverts one of the fundamental laws of inheritance by exploiting an ancient molecular pathway. I...

Fruit flies of the genus Drosophila have been an attractive and effective genetic model organism since Thomas Hunt Morgan and colleagues made seminal discoveries with them a century ago. Work with Drosophila has enabled dramatic advances in cell and developmental biology, neurobiology and behavior, molecular biology, evolutionary and population genetics, and other fields. With more tissue types and observable behaviors than in other short-generation model organisms, and with vast genome data available for many species within the genus, the fly's tractable complexity will continue to enable exciting opportunities to explore mechanisms of complex developmental programs, behaviors, and broader evolutionary questions. This primer describes the organism's natural history, the features of sequenced genomes within the genus, the wide range of available genetic tools and online resources, the types of biological questions Drosophila can help address, and historical milestones.

Centromeres are essential chromosomal regions that mediate kinetochore assembly and spindle attachments during cell division. Despite their functional conservation, centromeres are among the most rapidly evolving genomic regions and can shape karyotype evolution and speciation across taxa. Although significant progress has been made in identifying centromere-associated proteins, the highly repetitive centromeres of metazoans have been refractory to DNA sequencing and assembly, leaving large gaps in our understanding of their functional organization and evolution. Here, we identify the sequence composition and organization of the centromeres of Drosophila melanogaster by combining long-read sequencing, chromatin immunoprecipitation for the centromeric histone CENP-A, and high-resolution chromatin fiber imaging. Contrary to previous models that heralded satellite repeats as the major functional components, we demonstrate that functional centromeres form on islands of complex DNA sequences enriched in retroelements that are flanked by large arrays of satellite repeats. Each centromere displays distinct size and arrangement of its DNA elements but is similar in composition overall. We discover that a specific retroelement, G2/Jockey-3 , is the most highly enriched sequence in CENP-A chromatin and is the only element shared among all centromeres. G2/Jockey-3 is also associated with CENP-A in the sister species D . simulans , revealing an unexpected conservation despite the reported turnover of centromeric satellite DNA. Our work reveals the DNA sequence identity of the active centromeres of a premier model organism and implicates retroelements as conserved features of centromeric DNA.