Two Tests of Y Chromosomal Variation in Male Fertility of Drosophila Melanogaster

Deficiency mapping with Y autosome translocations has shown that the Y chromosome of Drosophila melanogaster carries genes that are essential to male fertility. While the qualitative behavior of these lesions provides important insight into the physiological importance of the Y chromosome, quantitative variation in effects on male fertility among extant Y chromosomes in natural populations may have a significant effect on the evolution of the Y chromosome. Here a series of 36 Y chromosome replacement lines were tested in two ways designed to detect subtle variation in effects on male fertility and total male fitness. The first test involved crossing males from the 36 lines to an excess of females in an attempt to measure differences in male mating success (virility) and male fecundity. The second test challenged males bearing each of the 36 Y chromosomes to competition in populations with males bearing a standard, phenotypically marked (BsY) chromosome. These tests indicated that the Y chromosome lines did not differ significantly in either male fertility or total fitness, but that interactions with autosomes approached significance. A deterministic population genetic model was developed allowing Y autosome interaction in fertility, and it is shown that, consistent with the experimental observations, this model cannot protect Y-linked polymorphism.     

The Y chromosome as a target for acquired and amplified genetic material in evolution

The special properties of the Y chromosome stem form the fact that it is a non-recombining degenerate derivative of the X chromosome. The absence of homologous recombination between the X and the Y chromosome leads to gradual degeneration of various Y chromosome genes on an evolutionary timescale. The absence of recombination, however, also favors the accumulation of transposable elements on the Y chromosome during its evolution, as seen with both Drosophila and mammalian Y chromosomes. Alongside these processes, the acquisition and amplification of autosomal male benefit genes occur. This review will focus on recent studies that reveal the autosome-acquired genes on the Y chromosome of both Drosophila and humans. The evolution of the acquired and amplified genes on the Y chromosome is also discussed. Molecular and comparative analyses of Y-linked repeats in the Drosophila melanogaster genome demonstrate that there was a period of their degeneration followed by a period of their integration into RNAi silencing, which was beneficial for male fertility. Finally, the function of non-coding RNA produced by amplified Y chromosome genetic elements will be discussed.     

Two new Y-linked genes in Drosophila melanogaster

The Y chromosome and other heterochromatic regions present special challenges for genome sequencing and for the annotation of genes. Here we describe two new genes (ARY and WDY) on the Drosophila melanogaster Y, bringing its number of known single-copy genes to 12. WDY may correspond to the fertility factor kl-1.     

Lack of nucleotide polymorphism in the Y-linked sperm flagellar dynein gene Dhc-Yh3 of Drosophila melanogaster and D. simulans

We studied levels of intra- and interspecific nucleotide variation associated with a Y-linked gene in five members of the Drosophila melanogaster subgroup. Using published sequence for 348 bp of the Dhc-Yh3 gene, and degenerate PCR primers designed from comparisons of the sea urchin and Chlamydomonas flagellar dynein genes, we recovered a 1738-bp region in D. melanogaster. Analyses of sequence variation in a worldwide collection of 11 lines of D. melanogaster and 10 lines of D. simulans found only a single silent polymorphism in the latter species. The synonymous site divergence per site for Dhc-Yh3 is comparable to values for X and autosomal genes. Assuming a Wright-Fisher population model, the lack of variation is statistically less than expected using appropriately reduced estimates of theta from the X and autosomes. Because the Y chromosome encodes only six known genes, genetic hitchhiking associated with background selection is unlikely to explain this low variation. Conversely, adaptive hitchhiking, as associated with sex-ratio chromosomes, or a large variance in male fertility may reduce the polymorphism on the Y chromosome. Codon bias is very low, as seen for other genes in regions of low recombination.     

Y-Linked male sterile mutations induced by P element in Drosophila melanogaster.

The Y chromosome in Drosophila melanogaster is composed of highly repetitive sequences and is essential only in the male germ line. We employed P-element insertional mutagenesis to induce male sterile mutations in the Y chromosome. By using a combination of two modifiers of position effect variegation, adding an extra Y chromosome and increasing temperature, we isolated 61 P(ry+) elements in the Y chromosome. Six of these Y-linked insertions (approximately 10%) induced male sterile mutations that are mapped to two genes on the long and one on the short arms of the Y chromosome. These mutations are revertible to the wild type in a cell-autonomous and germ-line-dependent manner, consistent with previously defined Y-linked gene functions. Phenotypes associated with these P-induced mutations are similar to those resulting from deletions of the Y chromosome regions corresponding to the male fertility genes. Three alleles of the kl-3 gene on the Y long arm result in loss of the axonemal outer dynein arms in the spermatid tail, while three ks-2 alleles on the Y short arm induce defects at early postmeiotic stages. The recovery of the ms(Y) mutations induced by single P-element insertions will facilitate our effort to understand the structural and functional properties of the Y chromosome.     

The Drosophila simulans Y chromosome interacts with the autosomes to influence male fitness

The Y chromosome should degenerate because it cannot recombine. However, male‐limited transmission increases selection efficiency for male‐benefit alleles on the Y, and therefore, Y chromosomes should contribute significantly to variation in male fitness. This means that although the Drosophila Y chromosome is small and gene‐poor, Y‐linked genes are vital for male fertility in Drosophila melanogaster and the Y chromosome has large male fitness effects. It is unclear whether the same pattern is seen in the closely related Drosophila simulans. We backcrossed Y chromosomes from three geographic locations into five genetic backgrounds and found strong Y and genetic background effects on male fertility. There was a significant Y‐background interaction, indicating substantial epistasis between the Y and autosomal genes affecting male fertility. This supports accumulating evidence that interactions between the Y chromosome and the autosomes are key determinants of male fitness.     

Fine Mapping of Satellite DNA Sequences along the Y Chromosome of Drosophila Melanogaster: Relationships between Satellite Sequences and Fertility Factors

The entirely heterochromatic Y chromosome of Drosophila melanogaster contains a series of simple sequence satellite DNAs which together account for about 80% of its length. Molecular cloning of the three simple sequence satellite DNAs of D. melanogaster (1.672, 1.686 and 1.705 g/ml) revealed that each satellite comprises several distinct repeat sequences. Together 11 related sequences were identified and 9 of them were shown to be located on the Y chromosome. In the present study we have finely mapped 8 of these sequences along the Y by in situ hybridization on mitotic chromosome preparations. The hybridization experiments were performed on a series of cytologically determined rearrangements involving the Y chromosome. The breakpoints of these rearrangements provided an array of landmarks along the Y which have been used to localize each sequence on the various heterochromatic blocks defined by Hoechst and N-banding techniques. The results of this analysis indicate a good correlation between the N-banded regions and 1.705 repeats and between the Hoechst-bright regions and the 1.672 repeats. However, the molecular basis for banding does not appear to depend exclusively on DNA content, since heterochromatic blocks showing identical banding patterns often contain different combinations of satellite repeats. The distribution of satellite repeats has also been analyzed with respect to the male fertility factors of the Y chromosome. Both loop-forming (kl-5, kl-3 and ks-1) and non-loop-forming (kl-2 and ks-2) fertility genes contain substantial amounts of satellite DNAs. Moreover, each fertility region is characterized by a specific combination of satellite sequences rather than by an homogeneous array of a single type of repeat.(ABSTRACT TRUNCATED AT 250 WORDS)     

Identification in chromosome 8q11 of a region of homology with the g1 amplicon of the Y chromosome and functional analysis of the BEYLA gene

The male-specific region (MSY) of the Y chromosome contains genes involved mainly in male sex determination and in spermatogenesis. The majority of genes involved in male fertility are localized in multiple copies in the long arm of the Y chromosome, within specific regions defined as "ampliconic regions." It has been suggested that these genes derived from X-linked or autosomal ancestors during evolution, providing a benefit for male fertility when transposed onto the Y chromosome. So far, the autosomal origin has been demonstrated only for two MSY genes, DAZ and CDY. In the present study we report on the identification within chromosome 8q11.2 of a region homologous to the g amplicon, containing the VCY2 (approved gene symbol BPY2), TTTY4, and TTTY17 genes. A search for ancestor genes within the 8q11.2 region allowed us to identify a gene named BEYLA and to characterize the genomic organization and the expression patterns of this gene.     

Adaptive co‐evolution of mitochondria and the Y‐chromosome: A resolution to conflict between evolutionary opponents

In most species with motile sperm, male fertility depends upon genes located on the Y‐chromosome and in the mitochondrial genome. Coordinated adaptive evolution for the function of male fertility between genes on the Y and the mitochondrion is hampered by their uniparental inheritance in opposing sexes: The Y‐chromosome is inherited uniparentally, father to son, and the mitochondrion is inherited maternally, mother to offspring. Preserving male fertility is problematic, because maternal inheritance permits mitochondrial mutations advantageous to females, but deleterious to male fertility, to accumulate in a population. Although uniparental inheritance with sex‐restricted adaptation also affects genes on the Y‐chromosome, females lack a Y‐chromosome and escape the potential maladaptive consequences of male‐limited selection. Evolutionary models have shown that mitochondrial mutations deleterious to male fertility can be countered by compensatory evolution of Y‐linked mutations that restore it. However, direct adaptive coevolution of Y‐ and mitochondrial gene combinations has not yet been mathematically characterized. We use population genetic models to show that adaptive coevolution of Y and mitochondrial genes are possible when Y‐mt gene combinations have positive effects on male fertility and populations are inbred.     

Hybrid dysgenesis-induced Y chromosomal sterility in Drosophila melanogaster

Summary Dysgenic hybrids of Drosophila melanogaster were screened for the induction of mutations in the Y chromosomal fertility genes. Out of 2,417 Y chromosomes analysed 13 male steriles (ms (Y)) were isolated. This high rate of mutation is most probably due to the unusually large physical size of the fertility genes.     

Male sterility and meiotic drive associated with sex chromosome rearrangements in Drosophila. Role of X-Y pairing.

In Drosophila melanogaster, deletions of the pericentromeric X heterochromatin cause X-Y nondisjunction, reduced male fertility and distorted sperm recovery ratios (meiotic drive) in combination with a normal Y chromosome and interact with Y-autosome translocations (T(Y;A)) to cause complete male sterility. The pericentromeric heterochromatin has been shown to contain the male-specific X-Y meiotic pairing sites, which consist mostly of a 240-bp repeated sequence in the intergenic spacers (IGS) of the rDNA repeats. The experiments in this paper address the relationship between X-Y pairing failure and the meiotic drive and sterility effects of Xh deletions. X-linked insertions either of complete rDNA repeats or of rDNA fragments that contain the IGS were found to suppress X-Y nondisjunction and meiotic drive in Xh-/Y males, and to restore fertility to Xh-/T(Y;A) males for eight of nine tested Y-autosome translocations. rDNA fragments devoid of IGS repeats proved incapable of suppressing either meiotic drive or chromosomal sterility. These results indicate that the various spermatogenic disruptions associated with X heterochromatic deletions are all consequences of X-Y pairing failure. We interpret these findings in terms of a novel model in which misalignment of chromosomes triggers a checkpoint that acts by disabling the spermatids that derive from affected spermatocytes.     

Selection of DNA sequences from interval 6 of the human Y chromosome with homology to a Y chromosomal fertility gene sequence of Drosophila hydei

Summary An experimental approach towards the molecular analysis of the male fertility function, located in interval 6 of the human Y chromosome, is presented. This approach is not based on the knowledge of any gene product but on the assumption that the functional DNA structure of male fertility genes, evolutionary conserved with their position on the Y chromosome, may contain an evolutionary conserved frame structure or at least conserved sequence elements. We tested this hypothesis by using dhMiF1, a fertility gene sequence of the Y chromosome of Drosophila hydei, as a screening probe on a pool of cloned human Y-DNA sequences. We were able to select 10 human Y-DNA sequences of which 7 could be mapped to Y interval 6 (the pY6H sequence family). Since the only fertility gene of the human Y chromosome is mapped to the same Y interval, our working hypothesis seems to be strongly supported. Most interesting in this respect is the isolation of the Y-specific repetitive pY6H65 sequence. The pY6H65 locus extends to a length of at least 300 kb in Y interval 6 and has a locus-specific repetitive sequence organization, reminiscent of the functional DNA structure of Y chromosomal fertility genes of Drosophila. We identified the simple sequence family (CA)_n as one sequence element conserved between the Drosophila dhMiFi fertility gene sequence and the homologous human Y-DNA sequences.     

The sex chromosome that refused to die

Chromosomes that harbor dominant sex determination loci are predicted to erode over time--losing genes, accumulating transposable elements, degenerating into a functional wasteland and ultimately becoming extinct. The Drosophila melanogaster Y chromosome is fairly far along this path to oblivion. The few genes on largely heterochromatic Y chromosome are required for spermatocyte-specific functions, but have no role in other tissues. Surprisingly, a recent paper shows that divergent Y chromosomes can substantially influence gene expression throughout the D. melanogaster genome.1 These results show that variation on Y has an important influence on the deployment of the genome.     

Genetic basis of hybrid male sterility among three closely related species of Drosophila

The genetic basis of hybrid male sterility among three closely related species, Drosophila bipectinata, D. parabipectinata and D. malerkotliana has been investigated by using backcross analysis methods. The role of Y chromosome, major hybrid sterility (MHS) genes (genetic factors) and cytoplasm (non-genetic factor) have been studied in the hybrids of these three species. In the species pair, bipectinata--parabipectinata, Y chromosome introgression of parabipectinata in the genomic background of bipectinata and the reciprocal Y chromosome introgression were unsuccessful as all males in second backcross generation were sterile. Neither MHS genes nor cytoplasm was found important for sterility. This suggests the involvement of X-Y, X-autosomes or polygenic interactions in hybrid male sterility. In bipectinata--malerkotliana and parabipectinata--malerkotliana species pairs, Y chromosome substitution in reciprocal crosses did not affect male fertility. Backcross analyses also show no involvement of MHS genes or cytoplasm in hybrid male sterility in these two species pairs. Therefore, X- autosome interaction or polygenic interaction is supposed to be involved in hybrid male sterility in these two species pairs. These findings also provide evidence that even in closely related species, genetic interactions underlying hybrid male sterility may vary.     

Mitochondrial mutations may drive Y chromosome evolution

The human Y chromosome contains very low levels of nucleotide variation. It has been variously hypothesized that this invariance reflects historic reductions in the human male population, a very recent common ancestry, a slow rate of molecular evolution, an inability to evolve adaptively, or frequent selective sweeps acting on genes borne on the Y chromosome. We propose an alternative theory in which human Y chromosome evolution is driven by mutations in the maternally inherited mitochondrial genome, which impair male fertility and ultimately lead to a reduction in the effective population size (N(e)) and consequently the variability of the Y chromosome.