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In many taxa, males and females have unequal ratios of sex chromosomes to autosomes, which has resulted in the invention of diverse mechanisms to equilibrate gene expression between the sexes (dosage compensation). Failure to compensate for sex chromosome dosage results in male lethality in Drosophila. In Drosophila, a male-specific lethal (MSL) complex of proteins and noncoding RNAs binds to hundreds of sites on the single male X chromosome and up-regulates gene expression. Here we use population genetics of two closely related Drosophila species to show that adaptive evolution has occurred in all five protein-coding genes of the MSL complex. This positive selection is asymmetric between closely related species, with a very strong signature apparent in Drosophila melanogaster but not in Drosophila simulans. In particular, the MSL1 and MSL2 proteins have undergone dramatic positive selection in D. melanogaster, in domains previously shown to be responsible for their specific targeting to the X chromosome. This signature of positive selection at an essential protein-DNA interface of the complex is unexpected and suggests that X chromosomal MSL-binding DNA segments may themselves be changing rapidly. This highly asymmetric, rapid evolution of the MSL genes further suggests that misregulated dosage compensation may represent one of the underlying causes of male hybrid inviability in Drosophila, wherein the fate of hybrid males depends on which species' X chromosome is inherited. genetic conflict | McDonald-Kreitman test | X chromosome | spiroplasmal | retrotransposons

A large-effect QTL for divergence in sex-comb tooth number between Drosophila simulans and D. mauritiana was previously mapped to 73A-84AB. Here we identify genes that are likely contributors to this divergence. We first improved the mapping resolution in the 73A-84AB region using 12 introgression lines and 62 recombinant nearly isogenic lines. To further narrow the list of candidate genes, we assayed leg-specific expression and identified genes with transcript-level evolution consistent with a potential role in sex-comb divergence. Sex combs are formed on the prothoracic (front) legs, but not on the mesothoracic (middle) legs of Drosophila males. We extracted RNA from the prothoracic and mesothoracic pupal legs of two species to determine which of the genes expressed differently between leg types were also divergent for gene expression. Two good functional candidate genes, Scr and dsx, are located in one of our fine-scale QTL regions. In addition, three previously uncharacterized genes (CG15186, CG2016, and CG2791) emerged as new candidates. These genes are located in regions strongly associated with sex-comb tooth number differences and are expressed differently between leg tissues and between species. Further supporting the potential involvement of these genes in sex-comb divergence, we found a significant difference in sex-comb tooth number between co-isogenic D. melanogaster lines with and without P-element insertions at CG2791.

Genomic imprinting is a phenomenon by which the expression of an allele at a locus depends on the parent of origin. Two different two-locus evolutionary models are presented in which a second locus modifies the imprinting status of the primary locus, which is under differential selection in males and females. In the first model, a modifier allele that imprints the primary locus invades the population when the average dominance coefficient among females and males is > 1/2 and selection is weak. The condition for invasion is always heavily contingent upon the extent of dominance. Imprinting is more likely in the sex experiencing weaker selection only under some parameter regimes, whereas imprinting by either sex is equally likely under other regimes. The second model shows that a modifier allele that induces imprinting will increase when imprinting has a direct selective advantage. The results are not qualitatively dependent on whether the modifier locus is autosomal or X linked.

Sex chromosomes originate from pairs of autosomes that acquire controlling genes in the sex-determining cascade. Universal mechanisms apparently influence the evolution of sex chromosomes, because this chromosomal pair is characteristically heteromorphic in a broad range of organisms. To examine the pattern of initial differentiation between sex chromosomes, sequence analyses were performed on a pair of newly formed sex chromosomes in Drosophila americana. This species has neo-sex chromosomes as a result of a centromeric fusion between the X chromosome and an autosome. Sequences were analyzed from the Alcohol dehydrogenase (Adh), big brain (bib), and timeless (tim) gene regions, which represent separate positions along this pair of neo-sex chromosomes. In the northwestern range of the species, the bib and Adh regions exhibit significant sequence differentiation for neo-X chromosomes relative to neo-Y chromosomes from the same geographic region and other chromosomal populations of D. americana. Furthermore, a nucleotide site defining a common haplotype in bib is shown to be associated with a paracentric inversion [In(4)ab] on the neo-X chromosome, and this inversion suppresses recombination between neo-X and neo-Y chromosomes. These observations are consistent with the inversion acting as a recombination modifier that suppresses exchange between these neo-sex chromosomes, as predicted by models of sex chromosome evolution.

In mammals, male sex determination starts when the Y chromosome Sry gene is expressed within the undetermined male gonad. One of the earliest effect of Sry expression is to induce upregulation of Sox9 gene expression in the developing gonad. SOX9, like SRY, contains a high mobility group domain and is sufficient to induce testis differentiation in transgenic XX mice. Before sexual differentiation, SOX9 protein is initially found in the cytoplasm of undifferentiated gonads from both sexes. At the time of testis differentiation and anti-Mullerian hormone expression, it becomes localized to the nuclear compartment in males whereas it is down-regulated in females. In this report, we used NIH 3T3 cells as a model to examine the regulation of SOX9 nucleo-cytoplasmic shuttling. SOX9-transfected cells expressed nuclear and cytoplasmic SOX9 whereas transfected cells treated with the nuclear export inhibitor leptomycin B, displayed an exclusive nuclear localization of SOX9. By using SOX9 deletion constructs in green fluorescent protein fusion proteins, we identified a functional nuclear export signal sequence between amino acids 134 and 147 of SOX9 high mobility group box. More strikingly, we show that inhibiting nuclear export with leptomycin B in mouse XX gonads cultured in vitro induced a sex reversal phenotype characterized by nuclear SOX9 and anti-Mullerian hormone expression. These results indicate that SOX9 nuclear export signal is essential for SOX9 sex-specific subcellular localization and could be part of a regulatory switch repressing (in females) or triggering (in males) male-specific sexual differentiation.

To isolate the genes involved in mouse primordial germ cell (PGC) development, we carried out subtraction cDNA cloning between PGC-derived embryonic germ (EG) cells and inner cell mass-derived embryonic stem cells. Among the genes preferentially expressed in EG cells, we found a gene encoding a receptor tyrosine kinase ErbB3. By in situ hybridization and immunohistochemical staining, the expression of ErbB3 as well as that of ErbB2, a coreceptor for ErbB3, was detected in PGCs in genital ridges at 12.5 dpc (days postcoitum). The expression was, however, downregulated at 14.5 dpc when the PGCs underwent growth cessation. Neuregulin-(beta), a ligand for ErbB2 and ErbB3, was also expressed in genital ridges. In addition, a recombinant Neuregulin-(beta) enhanced the number of PGCs in 12.5-dpc embryos in culture. Taken together, these observations suggest that ErbB signaling controls the growth or survival of PGCs in genital ridges. Key Words: EG cell; ES cell; subtraction cDNA cloning; primordial germ cell; ErbB3; neuregulin.

Sex-determining mechanisms are highly variable between phyla. Only one example has been found in which structurally and functionally related genes control sex determination in different phyla: the sexual regulators mab-3 of Caenorhabditis elegans and doublesex of Drosophila both encode proteins containing the DM domain, a novel DNA-binding motif. These two genes control similar aspects of sexual development, and the male isoform of DSX can substitute for MAB-3 in vivo, suggesting that the two proteins are functionally related. DM domain proteins may also play a role in sexual development of vertebrates. A human gene encoding a DM domain protein, DMRT1, is expressed only in the testis in adults and maps to distal 9p24.3, a short interval that is required for testis development. Earlier in development we find that murine Dmrt1 mRNA is expressed exclusively in the genital ridge of early XX and XY embryos. Thus Dmrtl and Sry are the only regulatory genes known to be expressed exclusively in the mammalian genital ridge prior to sexual differentiation. Expression becomes XY-specific and restricted to the seminiferous tubules of the testis as gonadogenesis proceeds, and both Sertoli cells and germ cells express Dmrt1. Dmrt1 may also play a role in avian sexual development. In birds the heterogametic sex is female (ZW), and the homogametic sex is male (ZZ). Dmrt1 is Z-linked in the chicken. We find that chicken Dmrt1 is expressed in the genital ridge and Wolffian duct prior to sexual differentiation and is expressed at higher levels in ZZ than in ZW embryos. Based on sequence, map position, and expression patterns, we suggest that Dmrt1 is likely to play a role in vertebrate sexual development and therefore that DM domain genes may play a role in sexual development in a wide range of phyla. Key Words: sex determination; DM domain; Dmrt1; mab-3; doublesex.

By binding specific RNA transcripts, the Sex-lethal protein (SXL) governs sexual differentiation and dosage compensation in Drosophila melanogaster. To investigate the basis for RNA binding specificity, we determined the crystal structure of the tandem RNA recognition motifs (RRMs) of SXL. Both RRMs adopt the canonical RRM fold, and the 10-residue, interdomain linker shows significant disorder. In contrast to the previously determined structure of the two-RRM fragment of heterogeneous nuclear ribonucleoprotein Al, SXL displays no interdomain contacts between RRMs. These results suggest that the SXL RRMs are flexibly tethered in solution, and RNA binding restricts the orientation of RRMs. Therefore, the observed specificity for single-stranded, U-rich sequences does not arise from a predefined, rigid architecture of the isolated SXL RRMs.

The infinite island model has been studied with sex-differentiated gene flow. Identity measures have been derived. The expected difference in genetic differentiation of autosomal vs X-linked loci shows that sex-differentiated migration is possible and may help resolve questions. A difference between effective gene flow and the number of migrants adds to a possible disagreement between direct and indirect dispersal estimates.

The repressed state of homeotic genes in Drosophila is maintained by Polycomb genes, which mediate changes in higher-order chromatin structure. The fifth exon of the mouse homologue of Polycomb, M33, contains a homologic region shared by Drosophila and Xenopus. The deletion of the exon causes a loss of Polycomb function in Drosophila. A new study shows that disruption of M33 in mice results in some individuals showing male-to-female sex reversal and suggests that M33 deficiency may interfere with gonadal development.

Vegetative incompatibility in fungi results from the control of heterokaryon formation by the genes present at het loci. Coexpression of antagonistic het genes in the same hyphae leads to a lethal process. In Podospora anserina, self-incompatible strains containing nonallelic incompatible genes in the same nucleus are inviable as the result of a growth arrest and a lytic process. Mutations in suppressor genes (mod genes) can restore the viability. These mod mutations also interfere with developmental processes, which suggests common steps between the incompatibility reaction and cellular differentiation. The mod-A locus, responsible for growth arrest in the self-incompatible strains, is also involved in the control of the development of female organs. The mod-A gene was isolated. An open reading frame 687 amino acids long was identified. The MOD-A-encoded polypeptide is rich in proline residues, which are clustered in a domain containing a motif that displays similarity to SH3-binding motifs, which are known to be involved in protein-protein interactions. Construction of a strain deleted for mod-A confirmed that the product of this gene involved in differentiation is a key regulator of growth arrest associated with vegetative incompatibility.

A large-scale transposon tagging screen was conducted to identify pheromone-regulated Saccharomyces cerevisiae genes. Mating defects were observed in the novel genes FIG1, FIG2, KAR5/FIG3 and FIG4. Results suggest that several novel genes are specifically expressed during mating differentiation to regulate mating processes such as proper cell morphogenesis and cell fusion.

I. INTRODUCTION Fetal sexual differentiation relies on translation of chromosomal sex established at fertilization into gonadal sex and somatic sex as development proceeds. In cases where chromosomal, gonadal, and somatic [...]

DNA fingerprint analysis is being developed as an alternative to surgical methods and karyotyping for gender identification. Microsatellite DNA probes consisting of dinucleotide and trinucleotide repeats were tested for use in detecting sex-specific sequences in nine different species of birds. Results show that sex-specific patterns are dependent on the species type and the kind of probes used.

The transformer (tra) genes of Drosophila simulans, D. erecta, D. hydei and D. virilis were cloned and sequenced in order to identify evolutionary conserved regions within the gene. The tra gene is involved in somatic sexual differentiation. Sequence analysis showed an unusual level of tra divergence among the different Drosophila species. These rapidly evolving regions constitute most of the coding region. However, one continuous stretch of nine amino acids is conserved in the tra gene of Drosophila. This sequence may code for a cis-acting regulator of the sex-specific alternative splicing event.

The sex determination mechanisms of the fruit fly Drosophila melanogaster, the nematode Caenorhabditis elegans and the mouse, which are superficially similar but have different molecular and cellular bases, give an evolutionary perspective of sex determination in animals. Cybernetic convergence, or the arrival at similar solutions to the problems brought about by sexual differentiation using diverse molecular mechanisms, is a term used to describe the phenomenon. Further studies of other animals may reveal other cases of cybernetic convergence in regulatory mechanisms.

Hymenoptera are characterized by a haplo-diploid mechanism of sex determination. Females are diploid and males are haploid. However, in many species diploid males may occur if individuals are homozygous at a sex determining locus. Diploid males were found in three out of four populations (nest aggregations) of the primitively eusocial, halictine bee Lasioglossum zephyrum for which samples of males were examined electrophoretically. The frequency of diploid males was greater in a small, geographically isolated population (the 'Robinson' nest aggregation) than in a large population that had nearby neighboring populations (the 'Salmon Creek A' nest aggregation). In addition, the proportion of polymorphic loci was lower in the Robinson nest aggregation suggesting that a bottleneck event or loss of alleles due to small population size occurred in the Robinson population that involved a loss in the number of alleles at the sex determining locus.

IFN-[Tau] is a secretory product of trophectoderm of cattle, sheep, and their relatives and is expressed for a few days in early pregnancy after the blastocyst first forms. It serves to alert the mother that she is pregnant. A delayed or less than robust IFN-[Tau] signal is a likely cause of embryonic loss. Here we have determined whether blastocyst production of IFN-[Tau], which is encoded by a cluster of genes on chromosome 9, differs between the sexes in cattle, as assessed by culture of in vitro-derived embryos on two different media, one complex (tissue culture medium 199 supplemented with serum) with coculture support, the other relatively simple (synthetic oviductal fluid plus albumin). With both media, female blastocysts produced approximately double the amount of IFN-[Tau] as males, regardless of such variables as oocyte batch, blastocyst quality, hatching, and length of time in culture. However, in either tissue culture medium 199, which contains 5.5 mM D-glucose, or in synthetic oviductal fluid, in the presence but not in the absence of added glucose, significantly fewer female than male embryos were able to progress from the morula/early blastocyst stage to more advanced stages of development. It is possible that the differences between male and female embryos both in their production of IFN-[Tau] and in their ability to progress in development in glucose-rich media are manifestations of phenomena that occur in vivo and provide plasticity in embryo selection during early pregnancy.

C57BL/6J-T-associated sex reversal (B6-TAS) in XY mice results in ovarian development and involves (1) hemizygosity for Tas, a gene located in the region of Chromosome 17 deleted in [T.sup.hp] and [T.sup.Orl], (2) homozygosity for one or more B6-derived autosomal genes, and (3) the presence of the AKRY chromosome. Here we report results from experiments designed to investigate the Y chromosome component of this sex reversal. Testis development was restored in B6 [T.sup.Orl]/+ [XY.sup.AKR] mice carrying a Mus musculus Sry transgene. In addition, two functionally different classes of M. domesticus Sry alleles were identified among eight standard and two wild-derived inbred strains. One class, which includes AKR, did not initiate normal testis development in B6 [T.sup.Orl]/+ XY mice, whereas the other did. DNA sequence analysis of the Sty ORF and a 5' 800-bp segment divided these inbred strains into the same groups. Finally, we found that Sry is transcribed in B6 [T.sup.Orl]/+ [XY.sup.AKR] fetal gonads but at a reduced level. These results pinpoint Sry as the Y-linked component of B6-TAS. We hypothesize that the inability of specific M. domesticus Sty alleles to initiate normal testis development in B6 [T.sup.Orl]/+ [XY.sup.AKR] mice results from a biologically insufficient level of Sty expression, allowing the ovarian development pathway to proceed.

Transcriptional inactivation of one X chromosome in mammalian female somatic cells leads to condensation of the inactive X chromosome into the heterochromatic sex chromatin, or Barr body. Little is known about the molecular composition and structure of the Barr body or the mechanisms leading to its formation in female nuclei. Because human sera from patients with autoimmune diseases often contain antibodies against a variety of cellular components, we reasoned that some autoimmune sera may contain antibodies against proteins associated with the Barr body. Therefore, we screened autoimmune sera by immunofluorescence of human fibroblasts and identified one serum that immunostained a distinct nuclear structure with a size and nuclear localization consistent with the Barr body. The number of these structures was consistent with the number of Barr bodies expected in diploid female fibroblasts containing two to five X chromosomes. Immunostaining with the serum followed by fluorescence in situ hybridization with a probe against XIST RNA demonstrated that the major fluorescent signal from the autoantibody colocalized with XIST RNA. Further analysis of the serum showed that it stains human metaphase chromosomes and a nuclear structure consistent with the inactive X in female mouse fibroblasts. However, it does not exhibit localization to a Barr body-like structure in female mouse embryonic stem cells or in cells from female mouse E7.5 embryos. The lack of staining of the inactive X in cells from female E7.5 embryos suggests the antigen(s) may be involved in X inactivation at a stage subsequent to initiation of X inactivation. This demonstration of an autoantibody recognizing an antigen(s) associated with the Barr body presents a strategy for identifying molecular components of the Barr body and examining the molecular basis of X inactivation.

It has been shown previously that abnormal placental growth, i.e., hyper- and hypoplasia, occurs in crosses and backcrosses between different mouse (Mus) species. A locus that contributes to this abnormal development has been mapped to the X chromosome. Unexpectedly, an influence of fetal sex on placental development has been observed, in that placentas attached to male fetuses tended to exhibit a more pronounced phenotype than placentas attached to females. Here, we have analyzed this sex dependence in more detail. Our results show that differences between male and female placental weights are characteristic of interspecific matings and are not observed in intraspecific Mus musculus matings. The effect is retained in congenic lines that contain differing lengths of M. spretus-derived X chromosome. Expression of the X-linked gene Pgk1 from the maternal allele only and lack of overall activity of two paternally inherited X-linked transgenes indicate that reactivation or lack of inactivation of the paternal X chromosome in trophoblasts of interspecific hybrids is not a frequent occurrence. Thus, the difference between male and female placentas seems not to be caused by faulty preferential X-inactivation. Therefore, these data suggest that the sex difference of placental weights in interspecific hybrids is caused by interactions with the Y chromosome.

Sexual reproduction allows deleterious transposable elements to proliferate in populations, whereas the loss of sex, by preventing their spread, has been predicted eventually to result in a population free of such elements [Hickey, D. A. (1982) Genetics 101, 519-531]. We tested this expectation by screening representatives of a majority of animal phyla for LINE-like and gypsy-like reverse transcriptases and mariner/Tc1-like transposases. All species tested positive for reverse transcriptases except rotifers of the class Bdelloidea, the largest eukaryotic taxon in which males, hermaphrodites, and meiosis are unknown and for which ancient asexuality is supported by molecular genetic evidence. Mariner-like transposases are distributed sporadically among species and are present in bdelloid rotifers. The remarkable lack of LINE-like and gypsy-like retrotransposons in bdelloids and their ubiquitous presence in other taxa support the view that eukaryotic retrotransposons are sexually transmitted nuclear parasites and that bdelloid rotifers evolved asexually.

The Caenorhabditis elegans vulva develops from the progeny of three vulval precursor cells (VPCs) induced to divide and differentiate by a signal from the somatic gonad. Evolutionarily conserved Ras and Notch extracellular signaling pathways are known to function during this process. To identify novel loci acting in vulval development, we carried out a genetic screen for mutants having a protruding-vulva (Pvl) mutant phenotype. Here we report the initial genetic characterization of several novel loci: bar-1, pvl-4, pvl-5, and pvl-6. In addition, on the basis of their Pvl phenotypes, we show that the previously identified genes lin-26, mom-3/mig-14, egl-18, and sem-4 also function during vulval development. Our characterization indicates that (1) pvl-4 and pvl-5 are required for generation/survival of the VPCs; (2) bar-1, mom-3/mig-14, egl-18, and sem-4 play a role in VPC fate specification; (3) lin-26 is required for proper VPC fate execution; and (4) pvl-6 acts during vulval morphogenesis. In addition, two of these genes, bar-1 and mom-3/mig-14, are known to function in processes regulated by Wnt signaling, suggesting that a Wnt signaling pathway is acting during vulval development.

It has been suggested that sexual identity in the germline depends upon the combination of a nonautonomous somatic signaling pathway and an autonomous X chromosome counting system. In the studies reported here, we have examined the role of the sexual differentiation genes transformer (tra) and doublesex (dsx) in regulating the activity of the somatic signaling pathway. We asked whether ectopic somatic expression of the female products of the tra and dsx genes could feminize the germline of XY animals. We find that [Tra.sup.F] is sufficient to feminize XY germ cells, shutting off the expression of male-specific markers and activating the expression of female-specific markers. Feminization of the germline depends upon the constitutively expressed transformer-2 (tra-2) gene, but does not seem to require a functional dsx gene. However, feminization of XY germ cells by [Tra.sup.F] can be blocked by the male form of the Dsx protein ([Dsx.sup.M]). Expression of the female form of dsx, [Dsx.sup.F], in XY animals also induced germline expression of female markers. Taken together with a previous analysis of the effects of mutations in tra, tra-2, and dsx on the feminization of XX germ cells in XX animals, our findings indicate that the somatic signaling pathway is redundant at the level tra and dsx. Finally, our studies call into question the idea that a cell-autonomous X chromosome counting system plays a central role in germline sex determination.

In Drosophila melanogaster, the rDNA loci function in ribosome biogenesis and nucleolar formation and also as sex chromosome pairing sites in male meiosis. These activities are not dependent on the heterochromatic location of the rDNA, because euchromatic transgenes are competent to form nucleoli and restore pairing to rDNA-deficient X chromosomes. These transgene studies, however, do not address requirements for the function of the endogenous rDNA loci within the heterochromatin. Here we describe two chromosome rearrangements that disrupt rDNA functions. Both rearrangements are translocations that cause an extreme bobbed visible phenotype and XY nondisjunction and meiotic drive in males. However, neither rearrangement interacts with a specific Y chromosome, [Ymal.sup.+], that induces male sterility in combination with rDNA deletions. Molecular studies show that the translocations are not associated with gross rearrangements of the rDNA repeat arrays. Rather, suppression of the bobbed phenotypes by Y heterochromatin suggests that decreased rDNA function is caused by a chromosomal position effect. While both translocations affect rDNA transcription, only one disrupts meiotic XY pairing, indicating that there are different cis-acting requirements for rDNA transcription and rDNA-mediated meiotic pairing.

The SynMuv genes appear to be involved in providing a signal that inhibits vulval precursor cells from adopting vulval fates in Caenorhabditis elegans. One group of SynMuv genes, termed class B, includes genes encoding proteins related to the tumor suppressor Rb and RbAp48, a protein that binds Rb. Here, we provide genetic evidence that lin-13 behaves as a class B SynMuv gene. We show that null alleles of lin-13 are temperature sensitive and maternally rescued, resulting in phenotypes ranging in severity from L2 arrest (when both maternal and zygotic activities are removed at 25 [degrees]), to sterile Multivulva (when only zygotic activity is removed at 25 [degrees]), to sterile non-Multivulva (when both maternal and zygotic activities are removed at 15 [degrees]), to wild-type/class B SynMuv (when only zygotic activity is removed at 15 [degrees]). We also show that LIN-13 is a nuclear protein that contains multiple zinc fingers and a motif, LXCXE, that has been implicated in Rb binding. These results together suggest a role for LIN-13 in Rb-mediated repression of vulval fates.

Many single-locus, two-allele selection models of genomic imprinting have been shown to reduce formally to one-locus Mendelian models with a modified parameter for genetic dominance. One exception is the model where selection at the imprinted locus affects the sexes differently. We present two models of maternal inactivation with differential viability in the sexes, one with complete inactivation, and the other with a partial penetrance for inactivation. We show that, provided dominance relations at the imprintable locus are the same in both sexes, a globally stable polymorphism exists for a range of viabilities that is independent of the penetrance of imprinting. The conditions for a polymorphism are the same as in previous models with differential viability in the sexes but without imprinting and in a model of the paternal X-inactivation system in marsupials. The model with incomplete inactivation is used to illustrate the analogy between imprinting and dominance by comparing equilibrium bifurcation plots for fixed values of dominance and penetrance. We also derive a single expression for the dominance parameter that leaves the frequency and stability of equilibria unchanged for all levels of inactivation. Although an imprinting model with sex differences does not formally reduce to a nonimprinting scheme, close theoretical parallels clearly exist.

Sex determination in Hymenoptera is controlled by haplo-diploidy in which unfertilized eggs develop into fertile haploid males. A single sex determination locus with several complementary alleles was proposed for Hymenoptera [so-called complementary sex determination (CSD)]. Heterozygotes at the sex determination locus are normal, fertile females, whereas diploid zygotes that are homozygous develop into sterile males. This results in a strong heterozygote advantage, and the sex locus exhibits extreme polymorphism maintained by overdominant selection. We characterized the sex-determining region by genetic linkage and physical mapping analyses. Detailed linkage and physical mapping studies showed that the recombination rate is [is less than] 44 kb/cM in the sex-determining region. Comparing genetic map distance along the linkage group III in three crosses revealed a large marker gap in the sex-determining region, suggesting that the recombination rate is high. We suggest that a 'hotspot' for recombination has resulted here because of selection for combining favorable genotypes, and perhaps as a result of selection against deleterious mutations. The mapping data, based on long-range restriction mapping, suggest that the Q DNA-marker is within 20,000 bp of the sex locus, which should accelerate molecular analyses.

Spatial and mathematical abilities may be 'sex-limited' traits. A sex-limited trait has the same determinants of variation within the sexes, but the genetic or environmental effects would be differentially expressed in males and females. New advances in structural equation modeling allow means and variation to be estimated simultaneously. When these statistical methods are combined with a genetically informative research design, it should be possible to demonstrate that the genes influencing spatial and mathematical abilities are sex-limited in their expression. This approach would give an empirical confirmation of Geary's evolutionary speculations.