SUPPRESSION OF SEX-RATIO MEIOTIC DRIVE AND THE MAINTENANCE OF Y-CHROMOSOME POLYMORPHISM IN DROSOPHILA

Like several other species of Drosophila, D. quinaria is polymorphic for X-chromosome meiotic drive; matings involving males that carry a “sex-ratio” X chromosome (X^SR) result in the production of strongly female-biased offspring sex ratios (Jaenike 1996). A survey of isofemale lines of D. quinaria from several populations reveals that there is genetic variation for partial suppression of this meiotic drive. Crossing experiments show that there is Y-linked, and probably autosomal, variation for suppression of drive. Y-linked suppressors of X-chromosome drive have now been described in several species of Diptera. I develop a simple model for the maintenance of Y-chromosome polymorphism in species polymorphic for X-linked meiotic drive. One interesting feature of this model is that, if there is a stable Y-chromosome polymorphism, then the equilibrium frequency of the standard and sex-ratio X chromosomes is determined solely by Y-chromosome parameters, not by the fitness effects of the different X chromosomes on their carriers. This model suggests that Y-chromosome polymorphism may be easier to maintain than previously thought, and I hypothesize that karyotypic variation in Y chromosomes will be found to be associated with suppression of sex-ratio meiotic drive in other species of Drosophila.     

Evidence of susceptibility and resistance to cryptic X-linked meiotic drive in natural populations of Drosophila melanogaster

There is mounting evidence consistent with a general role of positive selection acting on the Drosophila melanogaster X-chromosome. However, this positive selection need not necessarily arise from forces that are adaptive to the organism. Nonadaptive meiotic drive may exist on the X-chromosome and contribute to forces of selection. Females from a reference D. melanogaster line, containing the X-linked marker white, were crossed to males from 49 isofemale lines established from seven African and five non-African natural populations to detect naturally occurring meiotic drive. Several lines exhibited a departure from expected Mendelian transmission of X-chromosomes to the third generation (F2) offspring, particularly those from hybrid African male parents. F2 viability was not correlated with skewed chromosomal inheritance. However, a significant difference in viability between cosmopolitan and tropical African crosses was observed. Recombination analysis supports the presence of a male-acting meiotic drive element near the centromeric region of the X-chromosome and putative recessive autosomal drive suppression. There is also evidence of another female-acting drive element linked to white. The possible role meiotic drive may contribute in shaping levels of genetic variation in D. melanogaster, and additional ways to test this hypothesis are discussed.     

Partial hyperploidy of the X-chromosome inDrosophila hydei leading to duplication of male gonadal and genital structures

Summary Introduction of two doses of the X-chromosomalw ^mCo duplication next to a normal X-chromosome in males ofD. hydei leads to duplication of testis tissue and structures derived from the male genital disc. The effect of this partial hyperploidy of the X-chromosome seems restricted to the male. We tentatively conclude that this part of the X-chromosome contains some factor(s) which may specifically affect the reproductive system and analia of males.     

Relative DNA content of normal and sex-ratio distorting spermatozoa of the mosquito,Aedes aegypti (L.)

Scanning microdensitometry inAedes aegypti (L.) has revealed an extended range of DNA levels among the spermatozoa of sex-ratio distorting males compared with their normal counterparts. Fewer than 1% of spermatozoa contain less than the 1C level of DNA but more than 20% include greater quantities. Since this variation is identified with morphologically abnormal spermatozoa, it is considered to be a direct consequence of preferential X-chromosome breakage during male meiosis and hence of meiotic drive.     

Dosage compensation of sex-linked genes in Drosophila melanogaster. The activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase in flies with normal and disturbed genetic balance

Summary The phenomenon of dosage compensation in Drosophila melanogaster which consists in doubling of the activity of the X-chromosome genes in males as compared to those in females was studied.The specific activities of 6-phosphogluconate dehydrogenase (6PGD) and glucose-6-phosphate dehydrogenase (G6PD) determined by the sex-linked structural genes Pgd and Zw respectively were studied in flies carrying duplications for different regions of the X-chromosome. The increase in dose of Pgd and Zw in females resulting from the addition of an extra X-chromosome or X-fragments leads to a proportional rise in the specific activities of 6PGD and G6PD. On the other had the addition to females of the X-chromosome carrying no Pgd gene or X-fragments lacking Pgd and Zw has no effect on the enzyme activities. Thus we failed to reveal in the X-chromosome any compensatory genes envisaged by Muller, which would repress sex-linked structural genes proportional to their dose.The 6PGD and G6PD levels in phenotypically male-like intersexes carrying two X-chromosomes and three autosome sets (2X3A) is 30% higher than in diploid (2X2A) or triploid (3X3A) females. However the specific activities of the enzymes in female-like intersexes are the same as in regular females. The levels of 6PGD and G6PD per one X-chromosome are 1.5–2.0 times higher in the intersexes than in the normal females and metafemales (3X2A). The results indicate that the level of expression of the X-chromosome is determined by the X:A ratio. It is suggested that the decreased X:A ratio in males is responsible for the hyperactivation of their X-chromosomes.     

X-inactivation and X-reactivation: epigenetic hallmarks of mammalian reproduction and pluripotent stem cells

X-chromosome inactivation is an epigenetic hallmark of mammalian development. Chromosome-wide regulation of the X-chromosome is essential in embryonic and germ cell development. In the male germline, the X-chromosome goes through meiotic sex chromosome inactivation, and the chromosome-wide silencing is maintained from meiosis into spermatids before the transmission to female embryos. In early female mouse embryos, X-inactivation is imprinted to occur on the paternal X-chromosome, representing the epigenetic programs acquired in both parental germlines. Recent advances revealed that the inactive X-chromosome in both females and males can be dissected into two elements: repeat elements versus unique coding genes. The inactive paternal X in female preimplantation embryos is reactivated in the inner cell mass of blastocysts in order to subsequently allow the random form of X-inactivation in the female embryo, by which both Xs have an equal chance of being inactivated. X-chromosome reactivation is regulated by pluripotency factors and also occurs in early female germ cells and in pluripotent stem cells, where X-reactivation is a stringent marker of naive ground state pluripotency. Here we summarize recent progress in the study of X-inactivation and X-reactivation during mammalian reproduction and development as well as in pluripotent stem cells.     

Meiotic studies of translocations causing male sterility in the mouse. II. Double heterozygotes for Robertsonian translocations.

Unusual meiotic behavior of the XY chromosome pair was observed in sterile male mice doubly heterozygous for two Robertsonian translocations, Rb(16.17)7Bnr and Rb(8.17)1Iem. Nonrandom association between the X chromosome and the translocation configuration, ascertained from the frequencies of relevant C-band contacts, was found in 9 of 10 sterile males. Besides the nonrandom association, the XY chromosomes showed signs of impaired condensation, as judged by measurement of their lengths at diakinesis/MI of the first meiotic division. In contrast, neither nonrandom contact nor decondensation of the XY chromosomes pair was found in fertile males heterozygous for a single Robertsonian translocation, Rb1Iem or Rb7Bnr. The present observations lend indirect support to the working hypothesis advanced previously, the assumption that interference with X-chromosome inactivation is a possible cause of spermatogenic breakdown in carriers of various male-sterile chromosomal transloations. Alternative explanations of the available data, which cannot be ruled out, are briefly discussed.     

Radiation-Sensitive Mutants of CAENORHABDITIS ELEGANS

Nine rad (for abnormal radiation sensitivity) mutants hypersensitive to ultraviolet light were isolated in the small nematode Caenorhabditis elegans. The mutations are recessive to their wild-type alleles, map to four of the six linkage groups in C. elegans and define nine new games named rad-1 through rad-9. Two of the mutants—rad-1 and rad-2—are very hypersensitive to X rays, and three—rad-2, rad-3 and rad-4—are hypersensitive to methyl methanesulfonate under particular conditions of exposure. The hypersensitivity of these mutants to more than one DNA-damaging agent suggests that they may be abnormal in DNA repair. One mutant—rad-5, a temperature-sensitive sterile mutant—shows an elevated frequency of spontaneous mutation at more than one locus; rad-4, which shows a cold-sensitive embryogenesis, reduces meiotic X-chromosome nondisjunction tenfold and partially suppresses some but not all mutations that increase meiotic X-chromosome nondisjunction; the viability of rad-6 hermaphrodites is half that of rad-6 males at 25°; and newly mature (but not older) rad-8 hermaphrodites produce many inviable embryo progeny. Meiotic recombination frequencies were measured for seven rad mutants and found to be close to normal.     

Sex chromosome inactivation in the male

Mammalian females have two X chromosomes, while males have only one X plus a Y chromosome. In order to balance X-linked gene dosage between the sexes, one X chromosome undergoes inactivation during development of female embryos. This process has been termed X-chromosome inactivation (XCI). Inactivation of the single X chromosome also occurs in the male, but is transient and is confined to the late stages of first meiotic prophase during spermatogenesis. This phenomenon has been termed meiotic sex chromosome inactivation (MSCI). A substantial portion (~15-25%) of X-linked mRNA-encoding genes escapes XCI in female somatic cells. While no mRNA genes are known to escape MSCI in males, ~80% of X-linked miRNA genes have been shown to escape this process. Recent results have led to the proposal that the RNA interference mechanism may be involved in regulating XCI in female cells. We suggest that some MSCI-escaping miRNAs may play a similar role in regulating MSCI in male germ cells.     

Male-Sex-Ratio Trait in Drosophila Pseudoobscura: Frequency of Autosomal Aneuploid Sperm

Males with the SR X chromosome show the "sex-ratio" (sr) phenotype in which they produce almost entirely daughters. The few sons (about 1%) are invariably sterile X/O males and result entirely from nullo-XY sperm. The "male-sex-ratio" (msr) phenotype is a modified form of sr in which SR/Y males produce a higher frequency of sterile X/O sons. The msr trait is due to the presence of the SR X-chromosome in males which are also homozygous for one or more autosomes from the L116 strain. Here the frequency of nullo-3 and diplo-3 sperm from msr males was measured by crossing to a compound-3 strain and found to be 13.8% and 3.2%, respectively, of the total viable sperm. The sr males produced very low levels of nullo-3 sperm at a frequency not different from control X/Y males and a slightly elevated frequency of diplo-3 sperm over X/Y males. The msr males were found to have only 12% the fecundity of sr males and in matings to cause a high frequency of brown inviable eggs. These results indicate that high rates of autosomal aneuploidy are not restricted to chromosome 3 but also occur for chromosomes 2, 4 and 5. The overall frequency of autosomal aneuploid sperm is estimated to be approximately 50%. Microscopic studies of meiosis in testes from msr males indicates meiotic nondisjunction and meiotic chromosome loss are responsible for the msr phenotype. Last, microscopic studies of sperm cysts from msr males reveal high levels of spermiogenic failure.     

Meiotic disjunction,sex-determination and embryonic lethality in an X-linked “Simple” translocation of the onion fly,Hylemya antiqua (Meigen)

It was shown that the translocation in study is X-linked. After testcrossing translocation heterozygous males they generally only produce translocation heterozygous daughters and normal sons. The small acrocentric chromosomes involved in the translocation appeared to be the sex-chromosomes. The X-chromosome has a secondary constriction which is missing in the (male determining) Y-chromosome. Meiotic orientation was studied in translocation heterozygous males and females. The alternate and adjacent I orientations were found in about equal frequencies. Further, numerical meiotic non-disjunction (two types) occurred in translocation heterozygous males (about 2%), but is much higher in females (18.7%). In (achiasmate) males the homologous centromeres predominantly regulate meiotic pairing, coorientation and disjunction, apparently independently of the chromosomal rearrangement. Disturbed telomere pairing in particular leading to reduced chiasma frequency most probably explains the high numerical non-disjunction in chiasmate females. A rather good relationship exists between the percentage “semi”-sterility (28%), scored as late embryonic lethals (eggs, 72 hrs.) and the percentage karyotypes (20%) in young eggs (8–16 hrs.) with a large chromosomal deficiency. The remaining sterility (8%) can be explained by the somewhat decreased viability of tertiary trisomics and duplication karyotypes at the end of the egg stage. This translocation behaves like a “simple” one.     

The chromosomes of tufted deer (Elaphodus cephalophus)

Mitotic and meiotic chromosome preparations of the tufted deer (Elaphodus cephalophus) were studied to elucidate the sex-chromosomal polymorphism evidenced by this species. Females had 2n = 46 or 47 chromosomes, whereas males had 2n = 47 or 48 chromosomes. An X;autosome translocation was identified by synaptonemal complex analysis of spermatocytes at pachytene and confirmed by the presence of a trivalent at diakinesis/metaphase I. The present work, in combination with earlier observations by others, indicates that E. cephalophus possesses a varied X-chromosome morphology involving an X;autosome translocation and addition of varying amounts of heterochromatin. It is speculated that sex-chromosome polymorphism may be responsible for the observed differences in diploid chromosome number of tufted deer.     

XY<Subscript>1</Subscript>Y<Subscript>2</Subscript> chromosome system in <Emphasis Type="Italic">Salinomys delicatus</Emphasis> (Rodentia,Cricetidae)

Salinomys delicatus is considered a rare species due to its restricted and patchy distribution, poor records and low abundances. It is also the phyllotine with the lowest known diploid chromosome number (2n = 18), however its sex chromosome system has never been described. Here, we studied the chromosomes of six females and three males with bands G, C, DAPI/CMA₃ and meiosis. In males, the chromosome number was 2n = 19, with one large metacentric X-chromosome and two medium-sized acrocentrics absent in females. The karyotype of females was the same as previously described (2n = 18, FN = 32), with X-chromosomes being metacentric and the largest elements of the complement. In males, the two acrocentrics and the large metacentric form a trivalent in meiotic prophase. This indicates that S. delicatus has XY₁Y₂ sex chromosomes, which is confirmed by G and DAPI bands. Constitutive heterochromatin (CH) is restricted to small pericentromeric blocks in all chromosomes. The X-chromosome shows the largest block of centromeric CH, which could favor the establishment of this X-autosome translocation. This sex chromosome system is rare in mammals and, compared with other phyllotine rodents, S. delicatus seems to have undergone a major chromosome restructuring during its karyotypic evolution.     

Meiotic sex chromosome inactivation in the marsupial Monodelphis domestica

In eutherian mammals, the X and Y chromosomes undergo meiotic sex chromosome inactivation (MSCI) during spermatogenesis in males. However, following fertilization, both the paternally (Xp) and maternally (Xm) inherited X chromosomes are active in the inner cell mass of the female blastocyst, and then random inactivation of one X chromosome occurs in each cell, leading to a mosaic pattern of X-chromosome activity in adult female tissues. In contrast, marsupial females show a nonrandom pattern of X chromosome activity, with repression of the Xp in all somatic tissues. Here, we show that MSCI also occurs during spermatogenesis in marsupials in a manner similar to, but more stable than that in eutherians. These findings support the suggestion that MSCI may have provided the basis for an early dosage compensation mechanism in mammals based solely on gametogenic events, and that random X-chromosome inactivation during embryogenesis may have evolved subsequently in eutherian mammals.     

Anomalous development and differential DNA replication in the X-Chromosome of a Drosophila hybrid

Male hybrids of the cross D. azteca x D. athabasca are larger (hybrid giant males) than their parents, whereas hybrid females are of the same size as the parental species. Microspectrophotometric measurements have shown that the larval polytene salivary gland chromosomes of hybrid giant males undergo one more endoreplication than those of their sisters or parents. Replication patterns of the larval salivary gland chromosomes were compared after pulse labeling with ³H-thymidine and autoradiography. In females of either species as well as of hybrids X-chromosomes and autosomes are equally labeled, i.e. all chromosome arms replicate synchronously. In males, however, often fewer sites are labeled on the X-chromosome than on the autosomes. In addition, in a significant number of nuclei from D. athabasca males and also from hybrid giant males the converse can also be observed: i.e. more sites are labeled on the X-chromosome than on the autosomes. The modified labeling patterns are interpreted as an indication of a time-shift in the replication of hemizygous X-chromosomes in males, in relation to the autosomes.     

Heterochromatin variation and spermatogenesis in Nesokia

A probable role of heterochromatin variation in male meiosis has been evaluated using fertile and infertile Indian mole rat males (Nesokia) with polymorphic X and/or Y chromosomes. A comprehensive study of tubular histology, meiotic progression, and X-Y chromosome pairing was undertaken. Despite heterochromatin variation, spermatogenesis was found to be complete in all individuals. Patterns of X-Y synaptonemal complex pairing varied considerably from extensive synapsis in individuals with a normal heterochromatin complement, through end-to-end synapsis, to X and Y univalents in those with different degrees of loss of heterochromatin. Changes in the gonadal histology corresponding to heterochromatin variation were also observed. Loss of some coding DNA sequences in polymorphic X-chromosomes otherwise located at specific sites in the X-chromosome heterochromatin have been linked directly to modifications of the reproductive process. This is thought to be mediated by an altered X-chromosome activity during spermatogenesis or regulation of other locus/loci involved in fertility or reproduction.