The genetic basis of Haldane's rule

'Haldane's rule', formulated by J. B. S. Haldane in 1922, states that: "When in the F1 offspring of two different animal races one sex is absent, rare, or sterile, that sex is the heterozygous [heterogametic] sex". His rule is now known to apply in mammals, lepidopterans, birds, orthopterans and dipterans. In Drosophila, for example, Bock cites 142 cases of interspecific hybridizations that produce one sterile and one fertile sex in the offspring, all but one of these crosses yielding sterile XY males and fertile XX females. Despite much speculation, however, the genetic basis of Haldane's rule remains unknown. Haldane himself rejected the simple explanation that males are innately more sensitive than females to the effects of hybridization because groups with heterogametic females (such as birds and butterflies) usually show female sterility in hybrids, so that heterogamety itself is the critical feature. He and others suggested that heterogametic infertility or inviability in hybrids arises by a genetic imbalance between X chromosomes and autosomes. An alternative explanation is that this syndrome is caused by a mismatch of X and Y chromosomes. Here I show that in the Drosophila melanogaster subgroup, Haldane's rule for fertility apparently arises from a genetic interaction between X and Y chromosomes and not from an imbalance between sex chromosomes and autosomes. This finding has important implications for understanding the evolution of interspecific reproductive isolation.     

A test of reciprocal X-Y interactions as a cause of hybrid sterility in Drosophila.

Elucidation of the nature of the gene interactions that underly the sterility of interspecific hybrids is important in evolutionary biology. The interactions between the heterospecific X and Y (or Z and W) chromosomes are often used as an explanation for two reasons. First, the fertility of the hybrids of the heterogametic sex is much more often affected than that of the homogametic sex (Haldane's rule) and X-Y interactions are specific to the heterogametic sex. Second, sex chromosomes, especially the X chromosome, are often considered to be of special importance in determining the fertility of hybrids. X-Y interactions have been addressed in studies of males with a heterospecific Y chromosome in a mixed genetic background. A more stringent test of the X-Y interaction model requires each X chromosome sterility factor to be tested separately for its interaction with the Y chromosome in a homogeneous background of the pure species. Here we report such a test of the X-Y interaction model and conclude that X-Y interactions should not be assumed to be the only or even the most common cause of hybrid sterility.     

Evidence from mosaic analysis of the masculinizing gene her-1 for cell interactions in C. elegans sex determination.

Sex in Caenorhabditis elegans is determined by a regulatory cascade of seven interacting autosomal genes controlled by three X-linked genes in response to the X chromosome-to-autosome (X/A) ratio. XX animals (high X/A) develop as self-fertile hermaphrodites, and XO animals (low X/A) develop as males. The activity of the first gene in the sex-determining cascade, her-1, is required for male sexual development. XO her-1 loss-of-function mutants develop as self-fertile hermaphrodites, whereas XX her-1 gain-of-function mutants develop as masculinized intersexes. By genetic mosaic analysis using a fused free duplication linking her-1 to a cell-autonomous marker gene, we show here that her-1 expression in a sexually dimorphic cell is neither necessary nor sufficient for that cell to adopt a male fate. Our results suggest that her-1 is expressed in many, possibly all, cells and that its gene product can function non-autonomously through cell interactions to determine male sexual development.     

太行山猕猴〔Macaca mulatta(Rhesus monkey)〕染色体组型分析

本文报道了太行山猕猴染色体组型的观察,并根据测试数据经统计分析,绘出染色体组型图及其相对长度、臂比指数和置信限。结果证明太行山猕猴和其它地区的猕猴,在染色体组型上无明显差异。     

方蝙蝠的染色体组型分析

<正> 国外对蝙蝠科、属中的各类蝙蝠的染色体组型进行了研究,其中尤以1967年和1968年的Baker,R·J,和Patton,J·L,工作较多。例如,按照Baker和Patton的工作,他们对不同属的十余种染色体组型易于区分的蝙蝠,进行了细致的研究并作了分析报导,染色体数目从2n=22至2n=50不等。如Myotis grisescens(Gray mytois);Mytois macrodactylus和Myotis Velifer(Cave bat)均为2n=44,Eptesicus fuscus(Big brown bat)     

有瓣类二蝇种(Diptera:Sarco-phagidae and Calliphoridae)的细胞遗传学特征

研究了两个有瓣蝇种的细胞遗传学特征。结果表明:棕尾别麻蝇核型为2n=12,8M+2SM+2m,XX/XY,性染色体为微小的点状;C带主要分布于常染色体的着丝粒和次缢痕,性染色体Y普遍深染而X淡染;G带数(2n)为88条。铜绿蝇核型为2n=12,12M,XX/XY;常染色体以中央型C带为主,性染色体呈不同程度的深染;G带数(2n)为107条(雄)或110条(雌)。两蝇种染色体均存在多个随体,C带带型呈分散、杂合、多态或不稳定性。结合有关资料,探讨了有瓣蝇类演化的细胞遗传学机制。     

Localization of the human GM-CSF receptor gene to the X-Y pseudoautosomal region

Mammalian sex chromosomes share a small terminal region of homologous DNA sequences, which pair and recombine during male meiosis. Alleles in this region can be exchanged between X and Y chromosomes and are therefore inherited as if autosomal. Genes from this so-called pseudoautosomal region (PAR) are present in two doses in both males and females, and escape inactivation of the X chromosome in females. Indirect evidence suggests that there must be several pseudoautosomal genes, and several candidates have been proposed. Until now, the only gene that has been unequivocally located in the PAR is MIC2, which encodes a cell-surface antigen of unknown function. We now report the localization of a gene of known function to this region--the gene for the receptor of the haemopoietic regulator, granulocyte-macrophage colony stimulating factor. The chromosomal localization of this gene may be important in understanding the generation of M2 acute myeloid leukaemia.     

Rsx is a metatherian RNA with Xist-like properties in X-chromosome inactivation

In female (XX) mammals, one of the two X chromosomes is inactivated to ensure an equal dose of X-linked genes with males (XY). X-chromosome inactivation in eutherian mammals is mediated by the non-coding RNA Xist. Xist is not found in metatherians (marsupials), and how X-chromosome inactivation is initiated in these mammals has been the subject of speculation for decades. Using the marsupial Monodelphis domestica, here we identify Rsx (RNA-on-the-silent X), an RNA that has properties consistent with a role in X-chromosome inactivation. Rsx is a large, repeat-rich RNA that is expressed only in females and is transcribed from, and coats, the inactive X chromosome. In female germ cells, in which both X chromosomes are active, Rsx is silenced, linking Rsx expression to X-chromosome inactivation and reactivation. Integration of an Rsx transgene on an autosome in mouse embryonic stem cells leads to gene silencing in cis. Our findings permit comparative studies of X-chromosome inactivation in mammals and pose questions about the mechanisms by which X-chromosome inactivation is achieved in eutherians.     

An extrachromosomal factor causing loss of paternal chromosomes

Extrachromosomal inheritance is ubiquitous among plants and animals; however, most extrachromosomal factors are uniparentally inherited through females, but not through males. Examples include chloroplasts, mitochondria and a variety of intracellular symbionts. The only known exception to maternal extrachromosomal inheritance in an animal is a paternally transmitted sex ratio factor (psr) which causes all-male families in the parasitic wasp, Nasonia vitripennis. Normally in this wasp, male offspring are haploid and develop from unfertilized eggs whereas females are diploid and develop from fertilized eggs. The psr factor is either a venereally transmitted infection which prevents egg fertilization (and therefore causes all-male families), or a factor transmitted to eggs by the sperm of males carrying psr, which somehow prevents incorporation of the paternal chromosomes. Here we report that sperm from psr males fertilizes eggs, but that the paternal chromosomes are subsequently condensed into a chromatin mass before the first mitotic division of the egg and do not participate in further divisions. Resulting haploid offspring are male, but have inherited the paternal factor. This extrachromosomal factor promotes its own transmission at the expense of the paternal chromosomes, and therefore can be considered a 'selfish' genetic element.     

In the platypus a meiotic chain of ten sex chromosomes shares genes with the bird Z and mammal X chromosomes

Two centuries after the duck-billed platypus was discovered, monotreme chromosome systems remain deeply puzzling. Karyotypes of males, or of both sexes, were claimed to contain several unpaired chromosomes (including the X chromosome) that form a multi-chromosomal chain at meiosis. Such meiotic chains exist in plants and insects but are rare in vertebrates. How the platypus chromosome system works to determine sex and produce balanced gametes has been controversial for decades. Here we demonstrate that platypus have five male-specific chromosomes (Y chromosomes) and five chromosomes present in one copy in males and two copies in females (X chromosomes). These ten chromosomes form a multivalent chain at male meiosis, adopting an alternating pattern to segregate into XXXXX-bearing and YYYYY-bearing sperm. Which, if any, of these sex chromosomes bears one or more sex-determining genes remains unknown. The largest X chromosome, with homology to the human X chromosome, lies at one end of the chain, and a chromosome with homology to the bird Z chromosome lies near the other end. This suggests an evolutionary link between mammal and bird sex chromosome systems, which were previously thought to have evolved independently.     

Separation of the genetic loci for the H-Y antigen and for testis determination on human Y chromosome

The mammalian Y chromosome encodes a testis-determining factor (termed TDF in the human), a master regulator of sex differentiation. Embryos with a Y chromosome develop testes and become males whereas embryos lacking a Y chromosome develop ovaries and become females. Expression of H-Y, a minor histocompatibility antigen, may also be controlled by a gene on the Y chromosome, and it has been proposed that this antigen is the testis-determining factor. We have tested the postulated identity of H-Y and TDF in the human. H-Y typing with T cells was carried out on a series of sex-reversed humans (XX males and XY females), each shown by DNA hybridization to carry part but not all of the Y chromosome. This deletion analysis maps the gene for H-Y to the long arm or centromeric region of the human Y chromosome, far from the TDF locus, which maps to the distal short arm.     

A primitive Y chromosome in papaya marks incipient sex chromosome evolution

Many diverse systems for sex determination have evolved in plants and animals. One involves physically distinct (heteromorphic) sex chromosomes (X and Y, or Z and W) that are homozygous in one sex (usually female) and heterozygous in the other (usually male). Sex chromosome evolution is thought to involve suppression of recombination around the sex determination genes, rendering permanently heterozygous a chromosomal region that may then accumulate deleterious recessive mutations by Muller's ratchet, and fix deleterious mutations by hitchhiking as nearby favourable mutations are selected on the Y chromosome. Over time, these processes may cause the Y chromosome to degenerate and to diverge from the X chromosome over much of its length; for example, only 5% of the human Y chromosome still shows X-Y recombination. Here we show that papaya contains a primitive Y chromosome, with a male-specific region that accounts for only about 10% of the chromosome but has undergone severe recombination suppression and DNA sequence degeneration. This finding provides direct evidence for the origin of sex chromosomes from autosomes.     

Variation in regulation of steroid sulphatase locus in mammals

Inactivation (lyonization) of one of the two copies of X-linked genes occurs in female mammals, thereby reducing the number of active copies to that of the male. It has been suggested that genes subject to lyonization would be expected to be preserved as a linkage group during mammalian evolution. A short region of the human X chromosome containing several genes, including that necessary for the expression of steroid sulphatase (STS), is exceptional in that it apparently escapes X-inactivation. As it is not apparent why the linkage of genes not subject to X-inactivation should be conserved, we have examined the expression of the STS gene in mice (it has been shown recently that this gene is X-linked). Enzyme levels were determined in normal males and females and in the progeny of crosses in which the sex reversing factor, Sxr, was segregating to produce XX males. We report here that in contrast to the situation in humans, the STS gene in mice is subject to the normal pattern of X-inactivation.     

刺猬的染色体组型分析

<正> 国外对猬科猬属的两几地理亚种西欧刺猬(Erinaceus europaeus europaeus)和东欧刺猬(Erinaceus europaeus roumanicus)早在1968年由Geilser和Gropp就进行了染色体组型分析,两者在组型上有区别。本文对我国华北地区的刺猬(Erinaceus europaeuslinnaeus)的染色体组型进行了分析,就其结果来看,和欧洲刺猬在组型上是有差别的。华北地区的刺猬其染色体组型尚未见报导。     

Genetic evidence equating SRY and the testis-determining factor

The testis-determining factor gene (TDF) lies on the Y chromosome and is responsible for initiating male sex determination. SRY is a gene located in the sex-determining region of the human and mouse Y chromosomes and has many of the properties expected for TDF. Sex reversal in XY females results from the failure of the testis determination or differentiation pathways. Some XY females, with gonadal dysgenesis, have lost the sex-determining region from the Y chromosome by terminal exchange between the sex chromosomes or by other deletions. If SRY is TDF, it would be predicted that some sex-reversed XY females, without Y chromosome deletions, will have suffered mutations in SRY. We have tested human XY females and normal XY males for alterations in SRY using the single-strand conformation polymorphism assay and subsequent DNA sequencing. A de novo mutation was found in the SRY gene of one XY female: this mutation was not present in the patient's normal father and brother. A second variant was found in the SRY gene of another XY female, but in this case the normal father shared the same alteration. The variant in the second case may be fortuitously associated with, or predisposing towards sex reversal; the de novo mutation associated with sex reversal provides compelling evidence that SRY is required for male sex determination.     

Closely related sequences on human X and Y chromosomes outside the pairing region

During meiosis the human X and Y chromosomes form a synaptonemal complex which covers most of Yp and the terminal 30% of Xp (ref. 1). By analogy with the autosomes, this is presumed to reflect DNA sequence homology. It has been suggested that these regions of the X and Y chromosomes contain either related or identical loci which are distal to a site of cross-over, and support for these ideas has come from the finding that an X-linked cell-surface antigen controlling gene MIC2 is related to a gene on the Y chromosome. A number of DNA sequences have been shown to occur either on the X and Y chromosomes or on the X, Y and autosomes. We have now isolated a sequence from the Y chromosome which is present on Xq and Yq. This region lies well outside the pairing segments, and sequence analysis reveals no base change in 1 kilobase pair (kb). This high degree of similarity between the X and Y chromosomes near the tips of the long arms is a strong indication that interchange can occur in this region.