The Independent Distorting Ability of the Enhancer of Segregation Distortion, E(sd), in Drosophila Melanogaster

Segregation distortion is a meiotic drive system, discovered in wild populations, in which males heterozygous for an SD chromosome and a sensitive SD+ homolog transmit the SD chromosome almost exclusively. SD represents a complex of three closely linked loci in the centromeric region of chromosome 2: Sd, the Segregation distorter gene; E(SD), the Enhancer of Segregation Distortion, required for full expression of drive; and Rsp, the target for the action of Sd, existing in a continuum of states classifiable into sensitive (Rsps) and insensitive (Rspi). In an SD/SD+ male which is Sd E(SD) Rspi/Sd+ E(SD)+ Rsps, the Sd and E(SD) elements act jointly to induce the dysfunction of those spermatids receiving the Rsps chromosome. By manipulating the number of copies and the position of the Enhancer region, I demonstrated that: (1) E(SD), whether in its normal position or translocated to the Y chromosome, is able to enhance the degree of Sd-caused distortion in a dosage-dependent manner; (2) even in the absence of Sd, the E(SD) allele in two doses can cause significant distortion, in Sd+ or Df(Sd)-bearing genotypes; (3) quantitative differences among Enhancers of different sources suggest allelic variation at E(SD), which could account at least in part for differences among wild SD chromosomes in strength of distortion; (4) E(SD)/E(SD)-mediated distortion, like that of Sd, is directed at the Rsp target, whether Rsp is on the second or the Y chromosome; (5) E(SD), like Sd, is suppressed by an unlinked dominant suppressor of SD action. These results show that E(SD) is independently capable of acting on Rsp and is not a simple modifier of the action of Sd. E(SD) provides an example of a trans-acting gene embedded in heterochromatin that can interact with another heterochromatic gene, Rsp, as well as parallel the effect of a euchromatic gene, Sd.     

Negative Segregation Distortion in the Sd System of Drosophila Melanogaster: A Challenge to the Concept of Differential Sensitivity of Rsp Alleles

Current models of segregation distortion based on previous experimental results predict that, in the Sd heterozygous Rspi/Rsps male, the chromosome carrying the sensitive Rsps allele is distorted or transmitted in a frequency smaller than that of the expected Mendelian 0.5 relative to the chromosome carrying the insensitive Rspi allele. The present study presents a case where this does not occur, that is, when the genotype of the males is supp-X(SD)/Y; Sd E(SD)Rspi M(SD)+/Sd+ E(SD)+ Rsps M(SD)+ where supp-X(SD) is an X chromosome carrying a strong suppressor or suppressors of SD activity and SD+ E(SD)+ Rsps M(SD)+ is the standard cn bw chromosome. Following the "inseminated female transfer" procedure, young males of the above genotype carrying the standard-X instead of the supp-X(SD) chromosome show k values for the SD chromosome (frequencies of the SD chromosome recovered among progeny) of about 0.75, but with the supp-X(SD) chromosome, the k values are reduced to 0.36-0.41. Several possibilities other than the mechanism of segregation distortion to explain the reduced k values are ruled out. The occurrence of "negative segregation distortion" is clearly demonstrated, where the chromosome carrying the Rspi allele is distorted but the chromosome with the Rsps allele is not. This result requires a major modification of the current models or even a new model for the mechanism of segregation distortion to accommodate Rsp allele sensitivity or insensitivity. The present study also shows that males of the genotype, Sd Rspss M(SD)+/Sd+ Rspss M(SD), are almost completely sterile, but their fertility is considerably increased when SD activity is suppressed by the presence of the supp-X(SD) chromosome. This result suggests that the amount of the Sd product is not limited with respect to the interacting sites available, that is, the amount is large enough to interact with both of the Rspss alleles.     

Detection of Rsp and Modifier Variation in the Meiotic Drive System SEGREGATION DISTORTER (SD) of DROSOPHILA MELANOGASTER

Identification of allelic variability at the two major loci (Sd and Rsp) that interact to cause sperm dysfunction in Segregation distorter (SD) males of D. melanogaster has been hampered by the difficulty in separating the elements recombinationally. In addition, small differences in the strength of Sd alleles or sensitivities of Rsp alleles to Sd are difficult to measure against background genetic or environmental variation. Viability effects of the markers used to score progeny classes may also introduce a bias. Removal of Sd and E(SD) from their second chromosome location to create a Dp(2;Y)Sd E(SD) chromosome eliminates these problems, since any combination of Rsp alleles can be easily tested without resorting to recombinational techniques. Further, since these pairs of Rsp alleles are compared in their response to Dp Sd E(SD) in the same individual males, background variation and viability effects can be easily removed to allow fine-scale resolution of Rsp differences. Tests of all possible pairwise combination of six laboratory chromosomes in this way revealed at least three and possibly four different Rsp allelic classes. In addition, the hierarchical nature of the tests further allowed for determination of the presence of linked suppressors or enhancers of Sd activity. A sample of 11 second chromosomes selected from a group recently isolated from a natural population was also unambiguously ordered as to Rsp allelic status using this approach. The resultant pattern was similar to that obtained for the laboratory chromosomes, except for the not unexpected observation that the natural population apparently harbored more drive suppressors. The pattern of results obtained from these pairwise combinations of Rsp alleles supports the notion that there are no dominance interactions within the group, but that each responds more or less independently to Sd in giving sperm dysfunction.     

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.     

Biological parameters and the segregation distortion (SD) phenomenon in Drosophila melanogaster

The relationship between some biological parameters (mortality, longevity, fertility, fecundity and sex ratio) and segregation of second chromosomes in heterozygous and homozygous SD males has been analyzed. The results obtained in SD/SD+ heterozygous males show: (1) their reduced fertility with respect to that of control males, (2) an alteration in the sex ratio in the SD+ progeny only, and (3) inversely related sex-ratio and segregation distortion values. In SDi/SDj combinations: (1) surprisingly, fertility is intermediate between that of SD/SD+ heterozygous males and that of control males, (2) the segregation ratios of the second chromosomes are normal (0.50), and (3) the sex ratio = 0.50 in both classes of SD progeny. The relationship between mortality (and therefore longevity) and fertility of the different genotypes and fecundity per male indicates that the total productivity of heterozygous males is less than that so far claimed. Indeed, their productivity depends not only on the mechanism of nonformation of the SD+ sperm, but also on their reduced longevity. The k = 0.50 and the high fecundity of SDi/SDj combinations indicated that in these males the SD phenomenon is partially suppressed, the SD chromosomes being insensitive to each other, thus implying that particular Rsp alleles are sensitive to given Sd alleles. The complementation pattern for male fertility of SD homozygous males again supports previous evidence that Sd factors from natural populations are, in effect, different Sd genes.     

Cytogenetic Analysis of Segregation Distortion in Drosophila Melanogaster: The Cytological Organization of the Responder (Rsp) Locus

The segregation distortion phenomenon occurs in Drosophila melanogaster males carrying an SD second chromosome and an SD+ homolog. In such males the SD chromosome is transmitted to the progeny more frequently than the expected 50% because of an abnormal differentiation of the SD+-bearing sperms. Three major loci are involved in this phenomenon: SD and Rsp, associated with the SD and SD+ chromosome, respectively, and E(SD). In the present work we performed a cytogenetic analysis of the Rsp locus which was known to map to the centromeric heterochromatin of the second chromosome. Hoechst- and N-banding techniques were used to characterize chromosomes carrying Responder insensitive (Rspi), Responder sensitive (Rsps) and Responder supersensitive (Rspss) alleles. Our results locate the Rsp locus to the h39 region of 2R heterochromatin. This region is a Hoechst-bright, N-banding negative heterochromatic block adjacent to the centromere. Quantitative variations of the h39 region were observed. The degree of sensitivity to Sd was found to be directly correlated with the physical size of that region, demonstrating that the Rsp locus is composed of repeated DNA.     

Genealogical theory for random mating populations with two sexes

Consider a random mating population that has N(m) males and N(f) females in each generation. Let us assume that at time 0 a random sample of n copies of a gene is taken from this population. Then, for models introduced by Wright [Evolution in Mendelian populations, Genetics 16 (1931) 97; Inbreeding and homozygosis, Proc. Nat. Acad. Wash. 19 (1933) 420; Evolution and the Genetics of Populations, The Theory of Gene Frequencies, vol. II, The University of Chicago, Chicago and London, 1969.], it is possible to obtain generalizations of the haploid theory of genealogical processes developed by Felsenstein . It is conjectured that these hold generally, regardless of the effective population size, if n相似文献   

Studies of fs(1)1621, a mutation producing ovarian tumors in Drosophila melanogaster

The ethyl methane sulfonate-induced mutation, fs(1)1621, resides at 11.7 on the genetic map and within segment 4F1-5A1 of the cytological map of the X chromosome. When homozygous, fs(1)1621 renders females semisterile but has no effect on their viability; nor does it affect the viability or fertility of hemizygous males. Heterozygous females are fertile and have cytologically normal ovaries. The ovaries of homozygous females first produce normal oocytes, which, if fertilized, can develop into adult males or females. After this period, ovarian chambers containing only pseudonurse cells are formed, and finally mutant germaria produce only tumors. These contain hundreds to thousands of cells that appear to be derived from germarial cystocytes, because they occasionally form clones of interconnected cells and also can differentiate into endopolyploid pseudonurse cells. Raising the temperature speeds the rate at which tumors form; lowering it increases the probability of pseudonurse cell differentiation. Df(1)C159 includes fs(1)1621. The pattern of ovarian chamber production is more temperature sensitive in hemizygous females than in homozygous ones. The morphology of hemizygous tumors and the number of dividing cells within them also differ from homozygotes. These observations support the hypothesis that fs(1)1621 is producing a product, that less is produced by one gene than by two, and that the product plays a role in the mitosis and cytokinesis of ovarian cystocytes.     

Chromosome loss followed by duplication is the major mechanism of spontaneous mating-type locus homozygosis in Candida albicans

Candida albicans, which is diploid, possesses a single mating-type (MTL) locus on chromosome 5, which is normally heterozygous (a/alpha). To mate, C. albicans must undergo MTL homozygosis to a/a or alpha/alpha. Three possible mechanisms may be used in this process, mitotic recombination, gene conversion, or loss of one chromosome 5 homolog, followed by duplication of the retained homolog. To distinguish among these mechanisms, 16 spontaneous a/a and alpha/alpha derivatives were cloned from four natural a/alpha strains, P37037, P37039, P75063, and P34048, grown on nutrient agar. Eighteen polymorphic (heterozygous) markers were identified on chromosome 5, 6 to the left and 12 to the right of the MTL locus. These markers were then analyzed in MTL-homozygous derivatives of the four natural a/alpha strains to distinguish among the three mechanisms of homozygosis. An analysis of polymorphisms on chromosomes 1, 2, and R excluded meiosis as a mechanism of MTL homozygosis. The results demonstrate that while mitotic recombination was the mechanism for homozygosis in one offspring, loss of one chromosome 5 homolog followed by duplication of the retained homolog was the mechanism in the remaining 15 offspring, indicating that the latter mechanism is the most common in the spontaneous generation of MTL homozygotes in natural strains of C. albicans in culture.     

Computer simulation of genetic control. Comparison of sterile males and field-female killing systems

Summary A computer program, GENCON, designed to simulate genetic control using field-female killing systems, is described. These systems incorporate sex-linked translocations and conditional lethal mutations. Genetic death in field populations is caused by semisterility of the translocation and by homozygosis of the mutations in females and non-translocation males of field origin. Simulations using the program compare the effectiveness, in populations regulated by density, of genetic control using this type of system with control using sterile-male release. At high release rates, sterile males cause more rapid suppression and earlier eradication than sex-linked translocation strains. However, if releases are interrupted before eradication, the rate of recovery of density-dependent populations is more rapid following sterile-male release than following suppression with translocation strains. In such populations, the cumulative population suppression (number of individuals killed) is greater with translocation-strain release than with sterile-male release. At low release rates, sex-linked translocation strains can be much more effective at suppressing and eradicating density-dependent populations than sterile males. In continental Australia, eradication of the sheep blowfly Lucilia cuprina is probably not practicable. A suppression campaign using sex-linked translocation strains could yield a higher benefit to cost ratio than one using sterile males.     

Reduced X-linked rare polymorphism in males in comparison to females of Drosophila melanogaster

Natural selection is assumed to act more strongly on X-linked loci than on autosomal loci because the fitness effect of a recessive mutation on the X chromosome is fully expressed in hemizygous males. Therefore, selection is expected to fix or remove recessive mutations on the X chromosome more efficiently than those on autosomes. However, the assumption that hemizygosity of the X chromosome selectively accelerates changes in allele frequency has not been confirmed directly. To examine this assumption, we investigated current natural selection on X-linked chemoreceptor genes in a natural population of Drosophila melanogaster by comparing nucleotide diversity, linkage disequilibrium (LD), and departure from the neutrality in 4 chemoreceptor genes on 100 X chromosomes each from female and male flies. The general pattern of nucleotide diversity and LD for the genes investigated was similar in females and males. In contrast, males harbored significantly fewer rare polymorphisms defined as singletons and doubletons. When all the gene sequences were concatenated, Tajima's D showed a significant departure from the neutrality in both females and males, whereas Fu and Li's F* value revealed departure only in males. These results suggest that some rare polymorphisms on the X chromosome from females are recessively deleterious and are removed by stronger purifying selection when transferred to hemizygous males.     

Development of a genetic sexing strain of Anopheles arabiensis for KwaZulu‐Natal,South Africa

An efficient sexing system is important for the release of sterile males for any control programme using the sterile insect technique. This study describes the development and characterization of a new genetic sexing strain from South Africa (GMK), needed for the planned implementation of such a programme in northern KwaZulu‐Natal Province. The base colony used was a locally modified laboratory strain of Anopheles arabiensis containing a sex‐linked gene conferring dieldrin resistance to male mosquitoes. Female A. arabiensis mosquitoes from northern KwaZulu‐Natal were mated with these males and backcrossed to introduce the dieldrin resistance gene to the Y chromosome. The resulting strain therefore had an overall genotype representing the local population but with the Y chromosome containing the dieldrin resistance gene. Life‐history characteristics, stability of the sex‐linked resistance marker, and reduction in dieldrin waste were investigated. The strain showed semi‐sterility exhibited by low egg hatch rates, faster development in the immature stages and longer adult survivorship compared with the parental strains. While the GMK strain carrying the dieldrin‐resistant gene was successfully established, the stability of the gene is limited, requiring periodic purification. Dieldrin waste can be limited by treating many more eggs than currently recommended.     

Increased nondisjunction of chromosome 21 with age in human peripheral lymphocytes

Fluorescence in situ hybridization (FISH) on binucleated cells with chromosome-specific DNA probes provides a convenient way to visualize reciprocal segregation patterns in daughter nuclei, and overcomes most problems related to the artefactual loss or gain of chromosomes that flaw chromosome preparations. In this study, FISH was employed to evaluate age- and sex-effects on spontaneous malsegregation, nondisjunction and loss of chromosome 21 in human lymphocytes after the first division in culture. A total of 68 healthy nonsmokers and nondrinkers of alcohol (37 males and 31 females) were grouped by age as Group I (0-10 years), Group II (20-30 years), Group III (40-50 years) and Group IV (60-70 years), with at least seven subjects per group and sex. FISH with a pericentric chromosome 21 specific DNA probe was carried out on binucleated lymphocytes, cytokinesis-blocked by cytochalasin B (6 microg/ml for 26 h) at 44 h after initiation of cultures.Linear regression analyses demonstrated a significant age-related increase in the frequency of micronuclei without chromosome 21 (MN-21)(r=0.73, p<0.001 in females; r=0.69, p<0.001 in males) in all binucleated cells, with a steeper slope in females (0.1758) than in males (0. 1241). Analysis using the 2x2 chi-square (chi(2)) test on the frequencies of MN-21 showed significant age-related differences in both males and females, except males in Group III and Group IV (p>0. 05). A significant sex-related difference was found only in subjects over 60 years (p<0.05), with females having more MN-21 (12.57 per thousand vs. 8.43 per thousand) than males.Loss of chromosome 21, occurring at mean levels of 0.38 per thousand in all binucleated cells and 0.24 per thousand in binucleated cells containing four FISH signals, was shown not to be age- or sex-related. A positive age-related increase in nondisjunction of chromosome 21 was shown in males (r=0.50, p<0.01), females (r=0.61, p<0.001) and all subjects (r=0.55, p<0.001) by linear regression analysis. An age effect was found only between children and adults (p<0.01 for females, p<0.05     

Genetic sexing through the use of Y-linked transgenes

Sterile insect technique (SIT)-based pest control programs rely on the mass release of sterile insects to reduce the wild target population. In many cases, it is desirable to release only males. Sterile females may cause damage, e.g., disease transmission by mosquitoes or crop damage via oviposition by the Mediterranean fruit fly (Medfly). Also, sterile females may decrease the effectiveness of released males by distracting them from seeking out wild females. To eliminate females from the release population, a suitable sexual dimorphism is required. For several pest species, genetic sexing strains have been constructed in which such a dimorphism has been induced by genetics. Classical strains were based on the translocation to the Y chromosome of a selectable marker, which is therefore expressed only in males. Recently, several prototype strains have been constructed using sex-specific expression of markers or conditional lethal genes from autosomal insertions of transgenes. Here, we describe a novel genetic sexing strategy based on the use of Y-linked transgenes expressing fluorescent proteins. We demonstrate the feasibility of this strategy in a major pest species, Ceratitis capitata (Wiedemann), and discuss the advantages and disadvantages relative to other genetic sexing methods and potential applicability to other species.     

The spotted sterile male--a new mutation of dominant spotting on the mouse chromosome 5

Spotted sterile male - a new mutation in mice is described (tentative symbol Ssm). White spotting on the belly, legs and tail as well as sterility in heterozygous males Ssm/+ of the B10.M strain are caused by autosomal semidominant gene Ssm. The gene is localized on the 5 chromosome: the frequency of recombination between Ssm and go is 13.6 +/- 1.6%; Ssm is closely linked to Wv. The diheterozygotes Ssm+/+Wv are darkeyed white sterile mice. The deficiency of spermatogenic epithelium cells, emptyness of seminiferous tubules as well as interstitial tissue overgrowing occurred in the testis in sterile males Ssm/+ of B10.M. The fertile hybrid males Ssm/+ are obtained in outcrossing of females Ssm/+ of B10.M with males of YT/Y, CBA/CaY, DBA/2JY, A.CA/Y strains.     

The I-R system of hybrid dysgenesis in Drosophila melanogaster: influence on SF females sterility of their inducer and reactive paternal chromosomes.

A specific kind of sterile F1 female, denoted SF, arises when females from strains known as reactive are crossed with males from the complementary class of strains (inducer). It has been shown that this sterility results from the interaction between the maternal reactive cytoplasm and any one of the paternal inducer chromosomes. This interaction yields other dysgenic traits including non-disjunction and mutations. In this note, the abilities of paternal gametes containing various combinations of inducer and reactive chromosomes to give more or less sterile SF females when fertilising standard reactive oocytes were compared. Although they did not cause SF sterility, reactive chromosomes, when present in sperm containing at least one inducer chromosome, were found to influence the intensity of sterility: variations of SF sterility were observed between SF females which differed only by one paternally inherited reactive chromosome. Reactive chromosomes are known to control the cytoplasmic state of reactive females. The present results suggest that this chromosomal control also takes place in SF females.