A Two-Stage Model for the Control of rDNA Magnification

Males of the genotype bb/Ybb- have been shown to produce both magnified (bbm+) and, less frequently, reduced (bbrl) X chromosomes. An analysis of the progeny of single magnifying bb/Ybb- males reveals that bbm+ revertants may be recovered either as rare single events or, more frequently, in large clusters. To analyze the role of the bb phenotype in the induction of rDNA magnification we have constructed a series of bb and bb+ derivatives of Ybb-. Males carrying an X chromosomal bb allele and one of these derivatives (bb/bbYbb- or bb/bb+Ybb-) produce small numbers (one to two) of bbm+ progeny at a frequency similar to that observed for bb/Ybb- males but do not produce large clusters of bbm+ revertants. In addition, bb/bb+Ybb- males produce essentially equal numbers of magnified (bbm+) and reduced (bbrl) X chromosomes. These data, together with a consideration of the growth properties of the male germline in Drosophila, suggest that magnification/reduction may occur at two different times during development. Those events that give rise to large clusters, and, thus, necessarily arise early in germ cell development, appear to be dependent on the bb phenotype. However, those events that give rise to single bbm+ chromosomes arise late in spermatogenesis, probably at meiosis, and are independent of the bb phenotype.     

Magnification of the Ribosomal Genes in Female DROSOPHILA MELANOGASTER

The genetically induced increase in the number of 18S + 28S ribosomal genes known as magnification has been reported to occur in male Drosophila but has not previously been observed in females. We now report that bobbed magnified (bbm) is recovered in progeny of female Drosophila carrying three different X bobbed (Xbb) chromosomes and the helper XYbb chromosome, which is a derivative of the Ybb- chromosome. Using different combinations of bb or bb+ X and Y chromosomes, we show that magnification in females requires both a deficiency in ribosomal genes and the presence of a Y chromosome: X/X females that are rDNA-deficient but do not carry a Y chromosome do not produce bbm; similarly, X/X/Y females that carry a Y chromosome but are not rDNA-deficient do not produce bbm. Bobbed magnified is only recovered from rDNA-deficient X/XY, X/X/Y or XX/Y females. We have also found that females carrying a ring Xbb chromosome together with the XYbb- chromosome do not produce bbm, indicating that ring X chromosomes are inhibited to magnify in females as in males. We postulate that the requirement for a Y chromosome is due to sequences on the Y chromosome that regulate or encode factor(s) required for magnification, or alternatively, affect pairing of the ribosomal genes.--These studies demonstrate that magnification is not limited to males but also occurs in females. Magnification in females is induced by rDNA-deficient conditions and the presence of a Y chromosome, and probably occurs by a mechanism similar to that in males.     

The Effect of mei-41 on Rdna Redundancy in DROSOPHILA MELANOGASTER

The recombination and repair defective mutant, mei-41, exhibits three rather striking effects on the genetic properties and chromosomal stability of rDNA in Drosophila. First, mei-41 inhibits rDNA magnification. However, mei-9, another recombination and repair defective mutation has no similar effect. This indicates that magnification requires some, but not all, of the gene products necessary for meiotic exchange. Second, under magnifying conditions, mei-41 induces interchanges between the X rDNA and either arm of the Ybb- chromosome. These interchanges occur at high frequency and are independent of rDNA orientation. Third, in mei-41 bb+/Ybb+ males, bobbed mutants in the X, but not the Y, also arise at high frequency. Evidence suggests that these events involve the rDNA type I insertion. The recombination and repair defective properties of mei-41 together with our results regarding its unusual and specific effects involving rDNA are explained in a simple model that has general implications for chromosome structure.     

Molecular Characterization of Ribosomal Genes on the Ybb- Chromosome of DROSOPHILA MELANOGASTER

The question of whether the Ybb- chromosome contains ribosomal genes has been examined by using Southern blot analysis and comparing rDNA hybridization patterns for X/X and X/Ybb- DNA. The results demonstrate that the Ybb- chromosome contains sequences that hybridize to an rDNA probe under stringent conditions. Differential hybridization of some of these sequences with DNAs corresponding to different regions of a complete ribosomal gene repeat provides evidence that some of the genes on the Ybb- chromosome are type 2 repeats. Because data obtained by other workers suggest that type 2 repeats are transcribed only to low levels, these repeats may be classed as "nonfunctional". A further finding is that the ribosomal genes on the Ybb- chromosome do not undergo multiple rounds of DNA replication during polytenization of X/Ybb- cells.     

Genetic factors affecting normal growth of testes inDrosophila hydei

Summary A marked growth in the length of testes ofDrosophila hydei males occurred during pupal development. This growth continued over the first 8 days of adult life and in the young adults sperm were not produced until the testes increased approximately threefold in length to about 28 mm. The length of testes is correlated with genetic factors on the X and Y chromosomes. In males lacking a Y chromosome (X/O) or the short arm (Y^S) of the Y chromosome (X/Y^L) the testes were about half the length of testes of control males (X/Y) or double Y males (X/Y/Y). Males with deletions of the distal Y^L chromosome arm had testicular lengths equivalent to the controls. Males with short testes (X/O and X/Y^L) showed disruptions to spermatogenesis at meiosis and an absence of normal spermatid elongation. Reduction of active ribosomal RNA genes on the X chromosome in X/O caused an increased expression ofbobbed (bb) and a corresponding reduction in length of testes. Severelybobbed X/O males had very few cysts of spermatogonia and these cysts did not develop into primary spermatocytes.     

Inheritance of the snakeskin color pattern in the guppy, Poecilia reticulata

We made single-pair reciprocal crosses between the Green Snakeskin and Yellow Snakeskin domesticated strains of the guppy, Poecilia reticulata. The two snakeskin strains differ by a single autosomal gene, with the Green Snakeskin strain having the wild-type background coloration caused by the dominant gene (B), whereas the Yellow Snakeskin is homozygous for the recessive blond allele (bb). The snakeskin body and tail patterns characterizing males of these two strains are determined by two genes--Ssb and Sst--that are closely linked on the Y chromosome. The greenish-yellow tail color of the Green Snakeskin strain is mediated by an X-linked dominant gene, Grt. The recessive wild-type allele, Grt+, gives the hyaline tail color. In the Yellow Snakeskin strain, the Grt gene is expressed as a golden-yellow color as a result of the presence of the bb homozygous condition. The putative genotypes of the males and females of the Green Snakeskin strain are BB XGrt YSsb,Sst and BB XGrt XGrt, respectively. Males and females of the Yellow Snakeskin strain have the putative genotypes bb XGrt YSsb,Sst and bb XGrtXGrt, respectively. As a result of crossing over between the X and Y chromosomes, a few males and females of these two snakeskin strains may carry one or both snakeskin pattern genes (Ssb and Sst) on the X chromosome.     

Genetic Modulation of RNA Metabolism in Drosophila. IV. Measurement of Rates of RNA Synthesis by Density Labeling

Accumulation of RNA was measured in adult males of two genotypes: car bb/Ybb- and car bb/YbbSuVar-5. The two genotypes have similar amounts of rDNA, which is reduced in comparison to wild type (CLARK, STRAUSBAUGH and KIEFER 1977). Although genotypically bobbed, car bb/YbbSuVar-5 flies have a wild-type phenotype; car bb/Ybb- flies are both phenotypically and genotypically bobbed (CLARK, STRAUSBAUGH and KIEFER 1977). The wild-type phenotype observed in the car bb/YbbSuVar-5 flies is thought to be the result of an increased rate of rRNA synthesis due to the presence of the YbbSuVar-5 chromosome (SHERMOEN and KIFFER 1975; CLARK, STRAUSBAUGH and KIEFER 1977; CLARK and KIEFER 1977). To further define this phenomenon, the absolute accumulation of RNA was measured in the two genotypes, using density labeling methods. The accumulation of RNA is 1.4 to 1.8 times higher in car bb/YbbSuVar-5 flies than in car bb/Ybb- flies, demonstrating that there is genetic regulation of synthesis in this genotype. The use of density-labeled nucleosides has clearly shown that there is no difference in precusor pool sizes or use between the two genotypes studied.     

Y-chromosomal factor is involved in neonatal lethality in (♀ DDD × ♂DH-Dh/+) F1-Dh/+ male mice

The dominant hemimelia(Dh) mutation causes various developmental abnormalities in mice. Most -Dh/+ males, crosses between DDD females and DH-Dh/+ males, have lethal abnormalities during the neonatal period. This is a consequence of synergism among three independent gene loci; that is, theDh allele on chromosome (Chr) 1, the DDD allele on an X Chr-linked locus, and a Y Chr-linked locus in some strains. With regard to the Y Chr derived fromMus musculus musculus (M. m. musculus), the Y Chrs of C57BL/6J and BALB/cA caused lethality, but the Y Chr of C3H/HeJ did not, suggesting that not allM. m. musculus Y Chrs are the same. In the present study, whether Y Chrs derived fromM. m. domesticus andM. m. castaneus could cause lethality was investigated. Among seven inbred strains, including AKR/J, DDD, RF/J, SJL/J, SWR/J, TIRANO/Ei, and CAST/Ei, Y Chrs of AKR/ J, DDD, SJL/J, SWR/J, and TIRANO/Ei caused lethality, but Y Chrs of RF/J and CAST/Ei did not. It was unlikely that the mitochondrial genome of the DDD strain contributed to the lethality. The X Chr-linked locus could not compensate for the role of the Y Chr-linked locus. These results suggest that not allM. m. domesticus Y Chrs are the same.     

Autosomal Modifiers of the Bobbed Phenotype Are a Major Component of the Rdna Magnification Paradox in DROSOPHILA MELANOGASTER

rDNA magnification in Drosophila melanogaster is defined experimentally as the ability of bb/Ybb- males to produce exceptional progeny that are wild type with respect to rDNA associated phenotypes. Here, we show that some of these bobbed-plus progeny result not from genetic reversion at the bb locus but rather from variants at two or more autosomal loci that ameliorate the bobbed phenotype of rDNA deficient males in Drosophila. In doing so we resolve several aspects of a long-standing paradox concerning the phenomenon of rDNA magnification. This problem arose from the use of two genetic assays, which were presumed to be identical, but paradoxically, produced conflicting data on both the kinetics of reversion and the stability of magnified bb+ chromosomes. We resolve this problem by demonstrating that in one assay bobbed-plus progeny arise primarily by genetic reversion at the bobbed locus, whereas in the other assay bobbed-plus progeny arise both by reversion and by an epistatic effect of autosomal modifiers on the bobbed phenotype. We further show that such modifiers can facilitate the appearance of phenotypically bobbed-plus progeny even under conditions where genetic reversion is blocked by magnification defective mutants. Finally, we present a speculative model relating the action of these modifiers to the large increases in rDNA content observed in males undergoing magnification.     

One-Step and Stepwise Magnification of a BOBBED LETHAL Chromosome in DROSOPHILA MELANOGASTER

Bobbed lethal (bbl) chromosomes carry too few ribosomal genes for homozygous flies to be viable. Reversion of bbl chromosomes to bb or nearly bb+ occurs under magnifying conditions at a low frequency in a single generation. These reversions occur too rapidly to be accounted for by single unequal sister chromatid exchanges and seem unlikely to be due to multiple sister strand exchanges within a given cell lineage. Analysis of several one-step revertants indicates that they are X-Y recombinant chromosomes which probably arise from X-Y recombination at bb. The addition of ribosomal genes from the Y chromosome to the bbl chromosome explains the more rapid reversion of the bbl chromosome than is permitted by single events of unequal sister chromatid exchange. Analysis of stepwise bbl magnified chromosomes, which were selected over a period of 4-9 magnifying generations, shows ribosomal gene patterns that are closely similar to each other. Similarity in rDNA pattern among stepwise magnified products of the same parental chromosome is consistent with reversion by a mechanism of unequal sister strand exchange.     

Gene-Level,but Not Chromosome-Wide,Divergence between a Very Young House Fly Proto-Y Chromosome and Its Homologous Proto-X Chromosome

X and Y chromosomes are usually derived from a pair of homologous autosomes, which then diverge from each other over time. Although Y-specific features have been characterized in sex chromosomes of various ages, the earliest stages of Y chromosome evolution remain elusive. In particular, we do not know whether early stages of Y chromosome evolution consist of changes to individual genes or happen via chromosome-scale divergence from the X. To address this question, we quantified divergence between young proto-X and proto-Y chromosomes in the house fly, Musca domestica. We compared proto-sex chromosome sequence and gene expression between genotypic (XY) and sex-reversed (XX) males. We find evidence for sequence divergence between genes on the proto-X and proto-Y, including five genes with mitochondrial functions. There is also an excess of genes with divergent expression between the proto-X and proto-Y, but the number of genes is small. This suggests that individual proto-Y genes, but not the entire proto-Y chromosome, have diverged from the proto-X. We identified one gene, encoding an axonemal dynein assembly factor (which functions in sperm motility), that has higher expression in XY males than XX males because of a disproportionate contribution of the proto-Y allele to gene expression. The upregulation of the proto-Y allele may be favored in males because of this gene’s function in spermatogenesis. The evolutionary divergence between proto-X and proto-Y copies of this gene, as well as the mitochondrial genes, is consistent with selection in males affecting the evolution of individual genes during early Y chromosome evolution.     

The Evolution of the Y Chromosome with X-Y Recombination

A theoretical population genetic model is developed to explore the consequences of X-Y recombination in the evolution of sex chromosome polymorphism. The model incorporates one sex-determining locus and one locus subject to natural selection. Both loci have two alleles, and the rate of classical meiotic recombination between the loci is r. The alleles at the sex-determining locus specify whether the chromosome is X or Y, and the alleles at the selected locus are arbitrarily labeled A and a. Natural selection is modeled as a process of differential viabilities. The system can be expressed in terms of three recurrence equations, one for the frequency of A on the X-bearing gametes produced by females, one for each of the frequency of A on the X- and Y-bearing gametes produced by males. Several special cases are examined, including X chromosome dominance and symmetric selection. Unusual equilibria are found with the two sexes having very different allele frequencies at the selected locus. A significant finding is that the allowance of recombination results in a much greater opportunity for polymorphism of the Y chromosome. Tighter linkage results in a greater likelihood for equilibria with a large difference between the sex chromosomes in allele frequency.     

No evidence that Y‐chromosome differentiation affects male fitness in a Swiss population of common frogs

The canonical model of sex‐chromosome evolution assigns a key role to sexually antagonistic (SA) genes on the arrest of recombination and ensuing degeneration of Y chromosomes. This assumption cannot be tested in organisms with highly differentiated sex chromosomes, such as mammals or birds, owing to the lack of polymorphism. Fixation of SA alleles, furthermore, might be the consequence rather than the cause of recombination arrest. Here we focus on a population of common frogs (Rana temporaria) where XY males with genetically differentiated Y chromosomes (nonrecombinant Y haplotypes) coexist with both XY° males with proto‐Y chromosomes (only differentiated from X chromosomes in the immediate vicinity of the candidate sex‐determining locus Dmrt1) and XX males with undifferentiated sex chromosomes (genetically identical to XX females). Our study finds no effect of sex‐chromosome differentiation on male phenotype, mating success or fathering success. Our conclusions rejoin genomic studies that found no differences in gene expression between XY, XY° and XX males. Sexual dimorphism in common frogs might result more from the differential expression of autosomal genes than from sex‐linked SA genes. Among‐male variance in sex‐chromosome differentiation seems better explained by a polymorphism in the penetrance of alleles at the sex locus, resulting in variable levels of sex reversal (and thus of X‐Y recombination in XY females), independent of sex‐linked SA genes.     

Dosage Compensation in Mammals

Many organisms show major chromosomal differences between sexes. In mammals, females have two copies of a large, gene-rich chromosome, the X, whereas males have one X and a small, gene-poor Y. The imbalance in expression of several hundred genes is lethal if not dealt with by dosage compensation. The male–female difference is addressed by silencing of genes on one female X early in development. However, both males and females now have only one active X chromosome. This is compensated by twofold up-regulation of genes on the active X. This complex system continues to provide important insights into mechanisms of epigenetic regulation.     

Sexually dimorphic expression of the sex chromosome-linked genes cntfa and pdlim3a in the medaka brain

In vertebrates, sex differences in the brain have been attributed to differences in gonadal hormone secretion; however, recent evidence in mammals and birds shows that sex chromosome-linked genes, independent of gonadal hormones, also mediate sex differences in the brain. In this study, we searched for genes that were differentially expressed between the sexes in the brain of a teleost fish, medaka (Oryzias latipes), and identified two sex chromosome genes with male-biased expression, cntfa (encoding ciliary neurotrophic factor a) and pdlim3a (encoding PDZ and LIM domain 3 a). These genes were found to be located 3–4 Mb from and on opposite sides of the Y chromosome-specific region containing the sex-determining gene (the medaka X and Y chromosomes are genetically identical, differing only in this region). The male-biased expression of both genes was evident prior to the onset of sexual maturity. Sex-reversed XY females, as well as wild-type XY males, had more pronounced expression of these genes than XX males and XX females, indicating that the Y allele confers higher expression than the X allele for both genes. In addition, their expression was affected to some extent by sex steroid hormones, thereby possibly serving as focal points of the crosstalk between the genetic and hormonal pathways underlying brain sex differences. Given that sex chromosomes of lower vertebrates, including teleost fish, have evolved independently in different genera or species, sex chromosome genes with sexually dimorphic expression in the brain may contribute to genus- or species-specific sex differences in a variety of traits.     

Organization and Mapping of a Sequence on the DROSOPHILA MELANOGASTER X and Y Chromosomes That Is Transcribed during Spermatogenesis

The D. melanogaster DNA segment in the recombinant phage lambda Dm2L1 contains at least eight copies of a tandemly repeated 1250-base pair (bp) sequence (henceforth called the 2L1 sequence). Testes from XO D. melanogaster males contain an abundant 800-base RNA species that is homologous to a 520-bp region of the 2L1 sequence. Blotting experiments show that the 2L1 sequence is repeated in the D. melanogaster genome and is present on both the X and Y chromosomes. With the use of X-Y translocations, the 2L1 sequence has been mapped to a region between kl-1 and kl-2 on the long arm of the Y chromosome. In Oregon-R wild type there are an estimated 200 copies of the 2L1 sequence on the X chromosome and probably at least 80 copies of the Y chromosome. In some other strains the repetition frequency on the Y chromosome is about the same, but the copy number on the X chromosome is much reduced. On the basis of the five strains investigated, there is a correlation between copy number of the 2L1 sequence on the X chromosome and the presence of a particular allele of the Stellate locus (Ste; 1-45.7). It seems that low copy number corresponds to Ste+ and high copy number corresponds to Ste. The Ste locus determines whether single or star-shaped crystals are observed in the spermatocytes of XO males. Studies using D. simulans and D. mauritiana DNA show that the 2L1 sequence is homologous to restriction fragments in male DNA but not female DNA, indicating that this sequence is present only on the Y chromosome in these two species. In DNA derived from D. erecta, D. teissieri and D. yakuba, there is very little, if any, hybridization with the 2L1 sequence probe.