Segregation ratios within Segregation Distorter lines of Drosophila melanogaster conform to a beta-binomial distribution

Segregation Distorter (SD) chromosomes are preferentially recovered from SD/SD+ males due to the dysfunction of sperm bearing the SD+ chromosome. The proportion of offspring bearing the SD chromosome is given the symbol k. The nature of the frequency distribution of k was examined by comparing observed k distributions produced by six different SD chromosomes, each with a different mean, with k distributions predicted by two different statistical models. The first model was one where the k of all males with a given SD chromosome were considered to be equal prior to the determination of those gametes which produce viable zygotes. In this model the only source of variation of k would be binomial sampling. The results rigorously demonstrated for the first time that the observed k distributions did not fit the prediction that the only source of variation was binomial sampling. The next model tested was that the prior distribution of segregation ratios conformed to a beta distribution, such that the distribution of k would be a beta-binomial distribution. The predicted distributions of this model did not differ significantly from the observed distributions of k in five of the six cases examined. The sixth case probably failed to fit a beta-binomial distribution due to a major segregating modifier. The demonstration that the prior distribution of segregation ratios of SD lines can generally be approximated with a beta distribution is crucial for the biometrical analysis of segregation distortion.     

The Selfish Segregation Distorter Gene Complex of Drosophila melanogaster

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.     

Large-Scale Selective Sweep among Segregation Distorter Chromosomes in African Populations of Drosophila melanogaster

Segregation Distorter (SD) is a selfish, coadapted gene complex on chromosome 2 of Drosophila melanogaster that strongly distorts Mendelian transmission; heterozygous SD/SD⁺ males sire almost exclusively SD-bearing progeny. Fifty years of genetic, molecular, and theory work have made SD one of the best-characterized meiotic drive systems, but surprisingly the details of its evolutionary origins and population dynamics remain unclear. Earlier analyses suggested that the SD system arose recently in the Mediterranean basin and then spread to a low, stable equilibrium frequency (1–5%) in most natural populations worldwide. In this report, we show, first, that SD chromosomes occur in populations in sub-Saharan Africa, the ancestral range of D. melanogaster, at a similarly low frequency (~2%), providing evidence for the robustness of its equilibrium frequency but raising doubts about the Mediterranean-origins hypothesis. Second, our genetic analyses reveal two kinds of SD chromosomes in Africa: inversion-free SD chromosomes with little or no transmission advantage; and an African-endemic inversion-bearing SD chromosome, SD-Mal, with a perfect transmission advantage. Third, our population genetic analyses show that SD-Mal chromosomes swept across the African continent very recently, causing linkage disequilibrium and an absence of variability over 39% of the length of the second chromosome. Thus, despite a seemingly stable equilibrium frequency, SD chromosomes continue to evolve, to compete with one another, or evade suppressors in the genome.     

Satellite Ic: a possible link between the satellite DNAs of D. virilis and D. melanogaster.

In this study, we isolated and characterized a previously undetected cryptic satellite DNA comprising 0.1% of the total nuclear genome of D. virilis. This satellite is hidden from detection in neutral CsCl by satellite I and is therefore designated cryptic satellite I or Ic. Sequence analysis reveals that Ic is the repeating heptanucleotide [poly d(AATATAG): d(CTATATT)]. It is more closely related to the three simple sequence satellite DNAs of D. melanogaster, a distantly related species, than it is to any of the major D. virilis satellite DNA sequences. Ic may therefore be a link between the simple sequence satellites of D. virilis and D. melanogaster. As an extension of this theory, we have constructed a "family tree" linking the satellites of D. virilis and D. melanogaster by a series of "simple" operations. Only one intermediate required by this evolutionary scheme has not yet been identified.     

DNA Distribution in Spermatid Nuclei of Normal and Segregation Distorter Males of DROSOPHILA MELANOGASTER

Using the DNA-specific dye BAO [2,5-bis-(4'-aminophenyl-(1')]-1,3,4-oxadiazol), we have examined spermiogenesis in wild-type males of Drosophila melanogaster and in males carrying various combinations of the Sd and Rsp mutations involved in segregation distortion. Wild-type strains, even those newly collected from nature, are heterogeneous with respect to the incidence of spermiogenic abnormalities, principally in having a variable number of spermatid nuclei per cyst that fail to undergo complete elongation. Among segregation distorter males, Rsp/Rsp homozygotes have the greatest incidence of nuclear nonelongation or incomplete elongation, Rsp/Rsp ⁺ heterozygotes are intermediate, while Rsp⁺/ Rsp⁺ homozygotes have the least amount of abnormality. Indeed, Sd Rsp⁺/Sd⁺Rsp⁺ males have significantly fewer spermiogenic aberrations than do wild-type strains.     

Mutations to the piRNA Pathway Component Aubergine Enhance Meiotic Drive of Segregation Distorter in Drosophila melanogaster

Diploid sexual reproduction involves segregation of allelic pairs, ensuring equal representation of genotypes in the gamete pool. Some genes, however, are able to “cheat” the system by promoting their own transmission. The Segregation distorter (Sd) locus in Drosophila melanogaster males is one of the best-studied examples of this type of phenomenon. In this system the presence of Sd on one copy of chromosome 2 results in dysfunction of the non–Sd-bearing (Sd⁺) sperm and almost exclusive transmission of Sd to the next generation. The mechanism by which Sd wreaks such selective havoc has remained elusive. However, its effect requires a target locus on chromosome 2 known as Responder (Rsp). The Rsp locus comprises repeated copies of a satellite DNA sequence and Rsp copy number correlates with sensitivity to Sd. Under distorting conditions during spermatogenesis, nuclei with chromosomes containing greater than several hundred Rsp repeats fail to condense chromatin and are eliminated. Recently, Rsp sequences were found as small RNAs in association with Argonaute family proteins Aubergine (Aub) and Argonaute3 (AGO3). These proteins are involved in a germline-specific RNAi mechanism known as the Piwi-interacting RNA (piRNA) pathway, which specifically suppresses transposon activation in the germline. Here, we evaluate the role of piRNAs in segregation distortion by testing the effects of mutations to piRNA pathway components on distortion. Further, we specifically targeted mutations to the aub locus of a Segregation Distorter (SD) chromosome, using ends-out homologous recombination. The data herein demonstrate that mutations to piRNA pathway components act as enhancers of SD.     

中国黑腹果蝇中分离变相因子[Segregation Distorter(SD)]的初步研究

黑腹果蝇（Ｄｒｏｓｏｐｈｉｌａ ｍｅｌａｎｏｇａｓｔｅｒ）中的分离变相因子「Ｓｅｇｒｅｇａｔｉｏｎ Ｄｉｓｔｏｒｔｅｒ（ＳＤ）」是一种非常典型的具有减数分裂驱动性质的特殊遗传因子,ＳＤ在世界不同地区的黑腹果蝇群体中广泛存在,通过杂交的方法测得其频率在１％－５％范围之内。首次在中国北京,青岛采集大量野生黑腹果蝇样本,对ＳＤ进行频率测定,发现ＳＤ在中国野生黑腹果蝇群体中也广泛存在,且频率与世界其他地区     

Transposition of the Responder Element (Rsp) of the Segregation Distorter System (Sd) to the X Chromosome in Drosophila Melanogaster

In order to test whether the meiotic drive system Segregation distorter (SD) can operate on the X chromosome to exclude it from functional sperm, we have transposed the Responder locus (Rsp) to this element. This was accomplished by inducing detachments of a compound-X chromosome in females carrying a Y chromosome bearing a Rsps allele. Six Responder-sensitive-bearing X chromosomes, with kappa values ranging from 0.90 to 1.00, were established as permanent lines. Two of these have been characterized more extensively with respect to various parameters affecting meiotic drive. SD males with a Responder-sensitive X chromosome produce almost exclusively male embryos, while those with a Rsp-Y chromosome produce almost exclusively female embryos. This provides a genetic system of great potential utility for the study of early sex-specific differentiation events as it allows the collection of large numbers of embryos of a given sex.     

The Segregation Distorter (SD) complex and the accumulation of deleterious genes in laboratory strains of Drosophila melanogaster

Segregation Distorter (SD) associated with the second chromosome of D. melanogaster is found in nature at equilibrium frequencies lower than 5%. We report extremely high frequencies of SD (30–50%) in two selected strains, established in 1976, and show it to be responsible for the accumulation of deleterious genes in chromosome II. Samples of chromosomes extracted over a 4-year period were characterized with respect to distortion, sensitivity, lethality, sterility, and inversions. SD chromosomes were inversion-free as they have been shown to be in the Mediterranean area. The cosmopolitan inversion In(2L)t was found associated with SD ⁺ chromosomes. Lines polymorphic for SD have accumulated linked lethal and female-sterile genes approaching a near balanced system. It is proposed that deleterious genes linked in coupling to SD were accumulated by the balancing effect of distortion, while drift and restricted recombination account for the accumulation of deleterious genes linked in repulsion by a mechanism similar to Muller's ratchet. Our results should not be viewed as a particular case as SD chromosomes associated with detrimental genes and inversions are present in almost all populations around the world. The system could evolve in the way we describe whenever equilibrium conditions are broken down in small populations and lead to an increase in SD frequency.     

Sequence and sequence variation within the 1.688 g/cm3 satellite DNA of Drosophila melanogaster.

We have determined the complete nucleotide sequence of the monomer repeating unit of the 1.688 g/cm³ satellite DNA from Drosophila melanogaster. This satellite DNA, which makes up 4% of the Drosophila genome and is located primarily on the sex chromosomes, has a repeat unit 359 base-pairs in length. This complex sequence is unrelated to the other three major satellite DNAs present in this species, each of which contains a very short repeated sequence only 5 to 10 base-pairs long. The repeated sequence is more similar to the complex repeating units found in satellites of mammalian origin in that it contains runs of adenylate and thymidylate residues. We have determined the nature of the sequence variations in this DNA by restriction nuclease cleavage and by direct sequence determination of (1) individual monomer units cloned in hybrid plasmids, (2) mixtures of adjacent monomers from a cloned segment of this satellite DNA, (3) mixtures of monomer units isolated by restriction nuclease cleavage of total 1.688 g/cm³ satellite DNA. Both direct sequence determination and restriction nuclease cleavage indicate that certain positions in the repeat can be highly variable with up to 50% of certain restriction sites having altered recognition sequences. Despite the high degree of variation at certain sites, most positions in the sequence are highly conserved. Sequence analysis of a mixture of 15 adjacent monomer units detected only nine variable positions out of 359 base-pairs. Total satellite DNA showed only four additional positions. While some variability would have been missed due to the sequencing methods used, we conclude that the variation from one repeat to the next is not random and that most of the satellite repeat is conserved. This conservation may reflect functional aspects of the repeated DNA, since we have shown earlier that part of this sequence serves as a binding site for a sequence-specific DNA binding protein isolated from Drosophila embryos (Hsieh &; Brutlag, 1979).     

Nucleotide sequence of mouse satellite DNA.

The nucleotide sequence of uncloned mouse satellite DNA has been determined by analyzing Sau96I restriction fragments that correspond to the repeat unit of the satellite DNA. An unambiguous sequence of 234 bp has been obtained. The sequence of the first 250 bases from dimeric satellite fragments present in Sau96I limit digests corresponds almost exactly to two tandemly arranged monomer sequences including a complete Sau96I site in the center. This is in agreement with the hypothesis that a low level of divergence which cannot be detected in sequence analyses of uncloned DNA is responsible for the appearance of dimeric fragments. Most of the sequence of the 5% fraction of Sau96 monomers that are susceptible to TaqI has also been determined and has been found to agree completely with the prototype sequence. The monomer sequence is internally repetitious being composed of eight diverged subrepeats. The divergence pattern has interesting implications for theories on the evolution of mouse satellite DNA.     

Rates of DNA sequence evolution are not sex-biased in Drosophila melanogaster and D. simulans

To determine whether male- or female-biased mutation rates have affected the molecular evolution of Drosophila melanogaster and D. simulans, we calculated the male-to-female ratio of germline cell divisions ([symbol: see text]) from germline generation data and the male-to-female ratio of mutation rate ([symbol: see text]) by comparing chromosomal levels of nucleotide divergence. We found that the ratio of germline cell divisions changes from indicating a weak female bias to indicating a weak male bias as the age of reproduction increases. The range of [symbol: see text] values that we observed, however, does not lead us to expect much, if any, difference in mutation rate between the sexes. Silent and intron nucleotide divergence were compared between nine loci on the X chromosome and nine loci on the second and third chromosomes. The average levels of nucleotide divergence were not significantly different across the chromosomes, although both silent and intron sites show a trend toward slightly more divergence on the X. These results indicate a lack of sex- or chromosome-biased molecular evolution in D. melanogaster and D. simulans.      

Population Dynamics of the Segregation Distorter Polymorphism of DROSOPHILA MELANOGASTER

Two two-locus models of the population dynamics of the segregation distortion (SD) polymorphism of Drosophila melanogaster are described. One model is appropriate for understanding the population genetics of SD in nature, whereas the other is a special case appropriate for understanding an artificial population that has been extensively analysed. The models incorporate the general features of the Sd and Rsp loci which form the core of the SD system. It is shown that the SD polymorphism can be established only when there is sufficiently tight linkage between Sd and Rsp. An approximate treatment, valid for tight linkage, is given of all the equilibria of the system and their stabilities. It is shown that the observed composition of natural and artificial populations with respect to the Sd and Rsp loci is predicted well by the model, provided that restrictions are imposed on the fertilities of certain genotypes. Highly oscillatory paths towards equilibrium are usually to be expected on the basis of this model. The selection pressures on inversions introduced into this system are also investigated.