Aberrant chromosomal sex-determining mechanisms in mammals, with special reference to species with XY females

Both mouse and man have the common XX/XY sex chromosome mechanism. The X chromosome is of original size (5-6% of female haploid set) and the Y is one of the smallest chromosomes of the complement. But there are species, belonging to a variety of orders, with composite sex chromosomes and multiple sex chromosome systems: XX/XY1Y2 and X1X1X2X2/X1X2Y. The original X or the Y, respectively, have been translocated on to an autosome. The sex chromosomes of these species segregate regularly at meiosis; two kinds of sperm and one kind of egg are produced and the sex ratio is the normal 1:1. Individuals with deviating sex chromosome constitutions (XXY, XYY, XO or XXX) have been found in at least 16 mammalian species other than man. The phenotypic manifestations of these deviating constitutions are briefly discussed. In the dog, pig, goat and mouse exceptional XX males and in the horse XY females attract attention. Certain rodents have complicated mechanisms for sex determination: Ellobius lutescens and Tokudaia osimensis have XO males and females. Both sexes of Microtus oregoni are gonosomic mosaics (male OY/XY, female XX/XO). The wood lemming, Myopus schisticolor, the collared lemming, Dirostonyx torquatus, and perhaps also one or two species of the genus Akodon have XX and XY females and XY males. The XX, X*X and X*Y females of Myopus and Dicrostonyx are discussed in some detail. The wood lemming has proved to be a favourable natural model for studies in sex determination, because a large variety of sex chromosome aneuploids are born relatively frequently. The dosage model for sex determination is not supported by the wood lemming data. For male development, genes on both the X and the Y chromosomes are necessary.     

The origin of multiple sex chromosomes in the gerbil Gerbillus gerbillus (Rodentia: Gerbillinae)

The sex chromosomes of the partly sympatric species of gerbils Gerbillus pyramidum and G. gerbillus (Mammalia: Gerbillinae) were investigated by a variety of light- and electron-microscope methods, including DNA replication banding and synaptonemal complex (SC) techniques. The sex-chromosome mechanism of G. pyramidum is of the maleXY:femaleXX type, whereas that of G. gerbillus is of the less common maleXY1Y2:femaleXX system. The results include the demonstration that the X chromosomes of both species are compound. One segment is added to the X chromosome of G. pyramidum, leading to an increase in length from the standard 5% to approximately 7.3%, whereas two different extra segments increase the length of the X chromosome of G. gerbillus to approximately 11% of the length of the haploid genome. In both cases the extra material is autosomal and is also represented in the respective Y chromosomes. Classifying heterochromatin by the variation in staining quality was helpful in elucidating the possible origin of the different chromosome segments, including the pericentromeric regions. Observations on meiotic chromosome pairing and chiasma formation have confirmed the homologies established by band comparisons. The occurrence of chiasmata between the sex chromosomes supports the autosomal origin of the pairing segments. These and other findings have been interpreted in the framework of a multistep evolutionary model. This sequence starts from a hypothetical pair of sex chromosomes, the X element of which amounts to 5% of the haploid genome, and leads through three translocations involving two pairs of autosomes and one pericentric inversion to the most complex situation of this series, manifested in G. gerbillus. The adaptive value, if any, of autosome incorporation into the sex chromosomes repeatedly occurring here is unknown. It is, however, a remarkable fact that in one species, G. gerbillus, the complex sex-chromosome constitution is conserved over vast geographic distances, and in the other, G. pyramidum, the compound X and Y chromosomes withstand change in the face of extreme autosome restructuring.     

Genetics of sex determination in flowering plants

Most flowering plant species are hermaphroditic, but a small number of species in most plant families are unisexual (i.e., an individ-ual will produce only male or female gametes). Because species with unisexual flowers have evolved repeatedly from hermaphroditic progenitors, the mechanisms controlling sex determination in flowering plants are extremely diverse. Sex is most strongly determined by genotype in all species but the mechanisms range from a single controlling locus to sex chromosomes bearing several linked locirequired for sex determination. Plant hormones also influence sex expression with variable effects from species to species. Here, we review the genetic control of sex determination from a number of plant species to illustrate the variety of extant mechanisms. We emphasize species that are now used as models to investigate the molecular biology of sex determination. We also present our own investigations of the structure of plant sex chromosomes of white campion (Silene latifolia - Melan-drium album). The cytogenetic basis of sex determination in white campion is similar to mammals in that it has a male-specific Y-chromosome that carries dominant male determining genes. If one copy of this chromosome is in the genome, the plant is male. Otherwise it is female. Like mammalian Y-chromosomes, the white campion Y-chromosome is rich in repetitive DNA. We isolated repetitive sequences from microdissected Y-chromosomes of white campion to study the distribution of homologous repeated sequences on the Y-chromosome and the other chromosomes. We found the Y to be especially rich in repetitive sequences that were generally dispersed over all the white campion chromosomes. Despite its repetitive character, the Y-chromosome is mainly euchromatic. This may be due to the relatively recent evolution of the white campion sex chromosomes compared to the sex chromosomes of animals. © 1994 Wiley-Liss, Inc.     

THE CONTRIBUTION OF FEMALE MEIOTIC DRIVE TO THE EVOLUTION OF NEO‐SEX CHROMOSOMES

Sex chromosomes undergo rapid turnover in certain taxonomic groups. One of the mechanisms of sex chromosome turnover involves fusions between sex chromosomes and autosomes. Sexual antagonism, heterozygote advantage, and genetic drift have been proposed as the drivers for the fixation of this evolutionary event. However, all empirical patterns of the prevalence of multiple sex chromosome systems across different taxa cannot be simply explained by these three mechanisms. In this study, we propose that female meiotic drive may contribute to the evolution of neo‐sex chromosomes. The results of this study showed that in mammals, the XY₁Y₂ sex chromosome system is more prevalent in species with karyotypes of more biarmed chromosomes, whereas the X₁X₂Y sex chromosome system is more prevalent in species with predominantly acrocentric chromosomes. In species where biarmed chromosomes are favored by female meiotic drive, X‐autosome fusions (XY₁Y₂ sex chromosome system) will be also favored by female meiotic drive. In contrast, in species with more acrocentric chromosomes, Y‐autosome fusions (X₁X₂Y sex chromosome system) will be favored just because of the biased mutation rate toward chromosomal fusions. Further consideration should be given to female meiotic drive as a mechanism in the fixation of neo‐sex chromosomes.     

Synapsis and obligate recombination between the sex chromosomes of male laboratory mice carrying the Y* rearrangement.

The synaptic and recombinational behavior of the sex chromosomes in male laboratory mice carrying the Y* rearrangement was analyzed by light and electron microscopy. Examination of zygotene and pachytene X-Y* configurations revealed a surprising paucity of the staggered pairing configuration predicted from the distal position of the X pseudoautosomal region and the subcentromeric position of the Y* pseudoautosomal region. When paired at pachynema, the X and Y* chromosomes usually assumed configurations similar to those of typical sex bivalents from normal male laboratory mice. The X and Y* chromosomes were present as univalents in more than half of the early- and mid-pachytene nuclei, presumably as a result of steric difficulties associated with homologous alignment of the pseudoautosomal regions. When paired at diakinesis and metaphase I, the X and Y* chromosomes exhibited an asymmetrical chiasmatic association indicative of recombination within the staggered synaptic configuration. Both pairing disruption and recombinational failure apparently contribute to diakinesis/metaphase I sex-chromosome univalency, as most cells at these stages possessed X and Y* univalents lacking evidence of prior recombination. Recombinant X or Y* chromosomes were detected in all metaphase II complements examined, thus substantiating the hypothesis that X-Y recombination is a prerequisite for the normal progression of male meiosis.     

Chromosome banding in Amphibia. XXVI. Coexistence of homomorphic XY sex chromosomes and a derived Y-autosome translocation in Eleutherodactylus maussi (Anura,Leptodactylidae)

A 15-year cytogenetic survey on one population of the leaf litter frog Eleutherodactylus maussi in northern Venezuela confirmed the existence of multiple XXAA male symbol /XAA(Y) female symbol sex chromosomes which originated by a centric (Robertsonian) fusion between the original Y chromosome and an autosome. 95% of the male individuals in this population are carriers of this Y-autosome fusion. In male meiosis the XAA(Y) sex chromosomes pair in the expected trivalent configuration. In the same population, 5% of the male animals still possess the original, free XY sex chromosomes. In a second population of E. maussi analyzed, all male specimens are characterized by these ancestral XY chromosomes which form normal bivalents in meiosis. E. maussi apparently represents the first vertebrate species discovered in which a derived Y-autosome fusion still coexists with the ancestral free XY sex chromosomes. The free XY sex chromosomes, as well as the multiple XA(Y) sex chromosomes are still in a very primitive (homomorphic) stage of differentiation. With no banding technique applied it is possible to distinguish the Y from the X. DNA flow cytometric measurements show that the genome of E. maussi is among the largest in the anuran family Leptodactylidae. The present study also supplies further data on differential chromosome banding and fluorescence in situ hybridization experiments in this amphibian species.     

Did sex chromosome turnover promote divergence of the major mammal groups?

Comparative mapping and sequencing show that turnover of sex determining genes and chromosomes, and sex chromosome rearrangements, accompany speciation in many vertebrates. Here I review the evidence and propose that the evolution of therian mammals was precipitated by evolution of the male‐determining SRY gene, defining a novel XY sex chromosome pair, and interposing a reproductive barrier with the ancestral population of synapsid reptiles 190 million years ago (MYA). Divergence was reinforced by multiple translocations in monotreme sex chromosomes, the first of which supplied a novel sex determining gene. A sex chromosome‐autosome fusion may have separated eutherians (placental mammals) from marsupials 160 MYA. Another burst of sex chromosome change and speciation is occurring in rodents, precipitated by the degradation of the Y. And although primates have a more stable Y chromosome, it may be just a matter of time before the same fate overtakes our own lineage. Also watch the video abstract .     

XX/XY System of Sex Determination in the Geophilomorph Centipede Strigamia maritima

We show that the geophilomorph centipede Strigamia maritima possesses an XX/XY system of sex chromosomes, with males being the heterogametic sex. This is, to our knowledge, the first report of sex chromosomes in any geophilomorph centipede. Using the recently assembled Strigamia genome sequence, we identified a set of scaffolds differentially represented in male and female DNA sequence. Using quantitative real-time PCR, we confirmed that three candidate X chromosome-derived scaffolds are present at approximately twice the copy number in females as in males. Furthermore, we confirmed that six candidate Y chromosome-derived scaffolds contain male-specific sequences. Finally, using this molecular information, we designed an X chromosome-specific DNA probe and performed fluorescent in situ hybridization against mitotic and meiotic chromosome spreads to identify the Strigamia XY sex-chromosome pair cytologically. We found that the X and Y chromosomes are recognizably different in size during the early pachytene stage of meiosis, and exhibit incomplete and delayed pairing.     

The origin of mitotic sex-chromosome association in the brush-tailed possum, Trichosurus vulpecula (marsupalia:phalangeridae)

Nonrandom associations between the sex chromosomes of the brush-tailed possum, Trichosurus vulpecula, were found to be due to association of nucleolar organizer regions (NOR's) on the X and Y chromosomes. NOR association was also observed between an autosome and the X chromosome. These findings, based on silver staining, are in contrast to the report of MURRAY (1977), who observed sex-chromosome association in this animal and indicated that these nonrandom associations may reflect an association between heterochromatic regions during interphase. We observed only two pairs of NOR's per cell in this animal, one autosomal and one on the sex chromosomes, rather than the several such regions observed by MURRAY, who used an N-banding technique. We discuss the problem of nonhomologous chromosome association in mammalian cells as influenced by heterochromatin and NOR's and find little support for nonhomologous chromosome associations at mitotic metaphase due to heterochromatin association.     

Extensive sequence homologies between Y and other human chromosomes

Twenty-six human Y-chromosome-derived DNA sequences, free of repetitive material, were used to probe male and female genomic blots. We present data from a detailed analysis and chromosomal location of the bands detected by such probes, which demonstrate extensive DNA sequence homology between the mammalian sex chromosomes and autosomes. Under stringent conditions, nine Y-derived probes reacted exclusively with the Y chromosome, 12 probes detected homologous sequences present on both the Y and the X, four probes detected homologies between Y and autosome(s) without any X counterpart and, finally, one probe hybridized to homologous sequences on Y, X and autosome(s). These data are consistent with the hypothesis of a common evolutionary origin for the mammalian sex chromosomes and reveal structural similarities between Y-located and autosomal non-repetitive sequences.     

Sex difference in neural tube defects in p53-null mice is caused by differences in the complement of X not Y genes

To shed light on the biological origins of sex differences in neural tube defects (NTDs), we examined Trp53-null C57BL/6 mouse embryos and neonates at 10.5 and 18.5 days post coitus (dpc) and at birth. We confirmed that female embryos show more NTDs than males. We also examined mice in which the testis-determining gene Sry is deleted from the Y chromosome but inserted onto an autosome as a transgene, producing XX and XY gonadal females and XX and XY gonadal males. At birth, Trp53 nullizygous mice were predominantly XY rather than XX, irrespective of gonadal type, showing that the sex difference in the lethal effect of Trp53 nullizygosity by postnatal day 1 is caused by differences in sex chromosome complement. At 10.5 dpc, the incidence of NTDs in Trp53-null progeny of XY* mice, among which the number of the X chromosomes varies independently of the presence or absence of a Y chromosome, was higher in mice with two copies of the X chromosome than in mice with a single copy. The presence of a Y chromosome had no protective effect, suggesting that sex differences in NTDs are caused by sex differences in the number of X chromosomes.     

Chromosome studies in the red howler monkey, Alouatta seniculus stramineus (Platyrrhini, Primates): description of an X1X2Y1Y2/X1X1X2X2 sex-chromosome system and karyological comparisons with other subspecies

In the red howler monkey, Alouatta seniculus stramineus (2n = 47, 48, or 49), variations in diploid chromosome number are due to different numbers of microchromosomes. Males exhibit a Y;autosome translocation involving the short arm of an individual biarmed autosome. Consequently, the sex-chromosome constitution in the male is X1X2Y1Y2, with X1 representing the original X chromosome, X2 the biarmed autosome (No. 7), Y1 the Y;7p translocation product, and Y2 the acrocentric homolog of 7q. In the first meiotic division, a quadrivalent with a chain configuration can be observed in spermatocytes. Females have an X1X1X2X2 sex-chromosome constitution. Chromosome heteromorphisms were observed in pair 13, due to a pericentric inversion, and pair 19, due to the presence of constitutive heterochromatin. Microchromosomes, which varied in number between individuals, were also heterochromatic. NOR-staining was observed at two separate sites on a single chromosome pair (No. 10). A comparison of A.s. stramineus with A.s. macconnelli shows that these two subspecies have identical diploid chromosome numbers (47, 48, or 49), again due to a varying number of microchromosomes, and that they share a similar sex-chromosome constitution. Their karyotypes, however, are not identical, but can be derived from each other by a reciprocal translocation. Further comparisons with other A. seniculus subspecies reported in the literature indicate that this taxon is not karyologically uniform and that substantial chromosome shuffling has occurred between populations that have been considered to be subspecies by taxonomic criteria based on their morphometric attributes.     

The influence of the Robertsonian translocation Rb(X.2)2Ad on anaphase I non-disjunction in male laboratory mice

A Robertsonian translocation in the mouse between the X chromosome and chromosome 2 is described. The male and female carriers of the Rb(X.2)2Ad were fertile. A homozygous/hemizygous line was maintained. The influence of the X-autosomal Robertsonian translocation on anaphase I non-disjunction in male mice was studied by chromosome counts in cells at metaphase II of meiosis and by assessment of aneuploid progeny. The results conclusively show that the inclusion of Rb2Ad in the male genome induces non-disjunction at the first meoitic division. In second metaphase cells the frequency of sex-chromosomal aneuploidy was 10.8%, and secondary spermatocytes containing two or no sex chromosome were equally frequent. The Rb2Ad males sired 3.9% sex-chromosome aneuploid progeny. The difference in aneuploidy frequencies in the germ cells and among the progeny suggests that the viability of XO and XXY individuals is reduced. The pairing configurations of chromosomes 2, Rb2Ad and Y were studied during meiotic prophase by light and electron microscopy. Trivalent pairing was seen in all well spread nuclei. Complete pairing of the acrocentric autosome 2 with the corresponding segment of the Rb2Ad chromosome was only seen in 3.2% of the cells analysed in the electron microscope. The pairing between the X and Y chromosome in the Rb2Ad males corresponded to that in males with normal karyotype. Reasons for sex-chromosomal non-disjunction despite the normal pairing pattern between the sex chromosomes may be seen in the terminal chiasma location coupled with the asynchronous separation of the sex chromosomes and the autosomes.(ABSTRACT TRUNCATED AT 250 WORDS)     

The unique sex chromosome system in platypus and echidna

A striking example of the power of chromosome painting has been the resolution of the male platypus karyotype and the pairing relationships of the chain of ten sex chromosomes. We have extended our analysis to the nine sex chromosomes of the male echidna. Cross-species painting with platypus shows that the first five chromosomes in the chain are identical in both, but the order of the remainder are different and, in each species, a different autosome replaces one of the five X chromosomes. As the therian X is homologous mainly to platypus autosome 6 and echidna 16, and as SRY is absent in both, the sex determination mechanism in monotremes is currently unknown. Several of the X and Y chromosomes contain genes orthologous to those in the avian Z but the significance of this is also unknown. It seems likely that a novel testis determinant is carried by a Y chromosome common to platypus and echidna. We have searched for candidates for this determinant among the many genes known to be involved in vertebrate sex differentiation. So far fourteen such genes have been mapped, eleven are autosomal in platypus, two map to the differential regions of X chromosomes, and one maps to a pairing segment and is likewise excluded. Search for the platypus testis-determining gene continues, and the extension of comparative mapping between platypus and birds and reptiles may shed light on the ancestral origin of monotreme sex chromosomes.     

C-Banding/DAPI and in situ hybridization reflect karyotype structure and sex chromosome differentiation in Humulus japonicus Siebold & Zucc

Japanese hop (Humulus japonicus Siebold & Zucc.) was karyotyped by chromosome measurements, fluorescence in situ hybridization with rDNA and telomeric probes, and C-banding/DAPI. The karyotype of this species consists of sex chromosomes (XX in female and XY1Y2 in male plants) and 14 autosomes difficult to distinguish by morphology. The chromosome complement also shows a rather monotonous terminal distribution of telomeric repeats, with the exception of a pair of autosomes possessing an additional cluster of telomeric sequences located within the shorter arm. Using C-banding/DAPI staining and 5S and 45S rDNA probes we constructed a fluorescent karyotype that can be used to distinguish all autosome pairs of this species except for the 2 largest autosome pairs, lacking rDNA signals and having similar size and DAPI-banding patterns. Sex chromosomes of H. japonicus display a unique banding pattern and different DAPI fluorescence intensity. The X chromosome possesses only one brightly stained AT-rich terminal segment, the Y1 has 2 such segments, and the Y2 is completely devoid of DAPI signal. After C-banding/DAPI, both Y chromosomes can be easily distinguished from the rest of the chromosome complement by the increased fluorescence of their arms. We discuss the utility of these methods for studying karyotype and sex chromosome evolution in hops.     

Multiple sex-chromosome system in a loach fish

This study shows an X1X1X2X2/X1X2Y type of multiple sex-chromosome system in the genus Cobitis (Pisces, Ostariophysi). Observation of C-banded male meioses revealed that one arm of the neo-Y always associates end-to-end with one of the X chromosomes. This finding implies that a mechanism might be present that has prevented crossing-over between the ancestral X and Y chromosomes without morphological differentiation. This is the first reported case of multiple sex chromosomes among cyprinoid fish.     

EVOLUTIONARILY STABLE SEX RATIOS AND MUTATION LOAD

Frequency‐dependent selection should drive dioecious populations toward a 1:1 sex ratio, but biased sex ratios are widespread, especially among plants with sex chromosomes. Here, we develop population genetic models to investigate the relationships between evolutionarily stable sex ratios, haploid selection, and deleterious mutation load. We confirm that when haploid selection acts only on the relative fitness of X‐ and Y‐bearing pollen and the sex ratio is controlled by the maternal genotype, seed sex ratios evolve toward 1:1. When we also consider haploid selection acting on deleterious mutations, however, we find that biased sex ratios can be stably maintained, reflecting a balance between the advantages of purging deleterious mutations via haploid selection, and the disadvantages of haploid selection on the sex ratio. Our results provide a plausible evolutionary explanation for biased sex ratios in dioecious plants, given the extensive gene expression that occurs across plant genomes at the haploid stage.     

Verification of the structure of the complex sex chromosome system in Lagorchestes conspicillatus Gould (Marsupialia: Mammalia)

The complex sex chromosome system of Lagorchestes conspicillatus has been reinvestigated using G-banding, Hoechst 33258 sensitivity, and Ag staining. These investigations demonstrate that, as proposed, three exchanges have been involved in the evolution of this system. An autosome was translocated to the original X and the homologue of that autosome was translocated to the original Y. An additional autosome has been translocated to the Y. There is no sex vesicle at meiosis in the male, and no association between the original X and Y elements of the compound chromosomes. The inadequacies of the present terminology for complex sex chromosomes are considered and an alternative system suggested.     

Gender in plants: sex chromosomes are emerging from the fog

Although most plants have flowers with both male and female sex organs, there are several thousands of plant species where male or female flowers form on different individuals. Surprisingly, the presence of well-established sex chromosomes in these dioecious plants is rare. The best-described example is white campion, for which large sex chromosomes have been identified and mapped partially. A recent study presented a comprehensive genetic and physical mapping of the genome of dioecious papaya. It revealed a short male specific region on the Y chromosome (MSY) that does not recombine with the X chromosome, providing strong evidence that the sex chromosomes originated from a regular pair of autosomes. The primitive papaya Y chromosome thus represents an early event in sex chromosome evolution. In this article, we review the current status of plant sex-chromosome research and discuss the advantages of different dioecious models.     

X-ray induction of autosomal translocations in spermatozoa of Drosophila melanogaster and maternal effects of X.Y-chromosomes.

Wild-type ORK Drosophila melanogaster males were given an exposure of 3000 R X-radiation. Mature sperm were then sampled by mating to X.Y/X.Y, X.Y/X, or X/X females that carried markers on the second and third chromosomes for the detection of induced autosomal translocations. Two pairs of maternal stocks were used and heterozygous X.Y/X females were obtained by making both reciprocal crosses. The highest frequencies of induced translocations were obtained with X/X females. In one series these frequencies are higher than those obtained with either X.Y/X or X.Y/X.Y females. In the other series a uniform frequency of translocations was obtained with all types of female, except for one of the two types of heterozygous female, which gave lower frequencies. The experiments have provided data which show that the addition of Y-chromosomes to the maternal genome does not have a specific effect on the recovery of induced paternal autosomal translocations. Maternal Y-chromosomes increased the proportions of fertile F1 males, this effect being consistent in direction but varying in degree.