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1.
In mammals, the Y chromosome induces testis formation and thus male sexual development; in the absence of a Y chromosome, gonads differentiate into ovaries and female development ensues. Molecular genetic studies have identified the Y-located testis determining gene SRY as well as autosomal and X-linked genes necessary for gonadal development. The phenotypes resulting from mutation of these genes, together with their patterns of expression, provide the basis for establishing a hierachy of genes and their interactions in the mammalian sex determination pathway.  相似文献   

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Mammals have an XX:XY system of chromosomal sex determination in which a small heterochromatic Y controls male development. The Y contains the testis determining factor SRY, as well as several genes important in spermatogenesis. Comparative studies show that the Y was once homologous with the X, but has been progressively degraded, and now consists largely of repeated sequences as well as degraded copies of X linked genes. The small original X and Y have been enlarged by cycles of autosomal addition to one partner, recombination onto the other and continuing attrition of the compound Y. This addition–attrition hypothesis predicts that the pseudoautosomal region of the human X is merely the last relic of the latest addition. Genes (including SRY) on the conserved or added region of the Y evolved functions in male sex determination and differentiation distinct from the general functions of their X-linked partners. Although the gonadogenesis pathway is highly conserved in vertebrates, its control has probably changed radically and rapidly in vertebrate – even mammalian – evolution.  相似文献   

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There are many obvious morphological and behavioural differences between male and female Drosophila, whose differing phenotypes are produced by a hierarchy of sex determination genes. These genes have been well characterised at the genetic and molecular level. Similarly, a number of sex-specific differentiation genes have been characterised, such as the chorion and vitelline membrane genes in females and the sex peptide and other accessory gland proteins in males. Despite the depth of these parallel studies, there is only one example of a direct link between the sex determination pathway and the downstream sex differentiation genes, namely the regulation of the female-specific yolk protein genes. The yolk proteins are synthesised in the fat body and ovarian follicle cells of the adult female and are subsequently transported to the oocyte where they are stored for utilization during embrygenesis. The expression of the yolk protein genes is not entirely controlled by the sex determination hierarchy, as several different regulatory pathways must interact to direct their correct sexual, temporal and spatial regulation during development.  相似文献   

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Genetic mechanisms underlying male sex determination in mammals   总被引:1,自引:0,他引:1  
Genetic control of gonadal development proceeds through either the male or female molecular pathways, driving bipotential gonadal anlage differentiation into a testis or ovary. Antagonistic interactions between the 2 pathways determine the gonadal sex. Essentially sex determination is the enhancement of one of the 2 pathways according to genetic sex. Initially, Sry with other factors upregulatesSox9 expression in XY individuals. Afterwards the expression ofSox9 is maintained by a positive feedback loop withFgf9 and prostaglandin D2 as well as by autoregulative ability of Sox9. If these factors reach high concentrations, then Sox9 and/or Fgf9 may inhibit the female pathway. Surprisingly, splicing, nuclear transport, and extramatrix proteins may be involved in sex determination. The male sex determination pathway switches on the expression of genes driving Sertoli cell differentiation. Sertoli cells orchestrate testicular differentiation. In the absence of Sry, the predomination of the female pathway results in the realization of a robust genetic program that drives ovarian differentiation.  相似文献   

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Background  

Hormones are critical for early gonadal development in nonmammalian vertebrates, and oestrogen is required for normal ovarian development. In contrast, mammals determine sex by the presence or absence of the SRY gene, and hormones are not thought to play a role in early gonadal development. Despite an XY sex-determining system in marsupial mammals, exposure to oestrogen can override SRY and induce ovarian development of XY gonads if administered early enough. Here we assess the effect of exogenous oestrogen on the molecular pathways of mammalian gonadal development.  相似文献   

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Investigations of genetic diversity and domestication in South American camelids (SAC) have relied on autosomal microsatellite and maternally‐inherited mitochondrial data. We present the first integrated analysis of domestic and wild SAC combining male and female sex‐specific markers (male specific Y‐chromosome and female‐specific mtDNA sequence variation) to assess: (i) hypotheses about the origin of domestic camelids, (ii) directionality of introgression among domestic and/or wild taxa as evidence of hybridization and (iii) currently recognized subspecies patterns. Three male‐specific Y‐chromosome markers and control region sequences of mitochondrial DNA are studied here. Although no sequence variation was found in SRY and ZFY, there were seven variable sites in DBY generating five haplotypes on the Y‐chromosome. The haplotype network showed clear separation between haplogroups of guanaco–llama and vicuña–alpaca, indicating two genetically distinct patrilineages with near absence of shared haplotypes between guanacos and vicuñas. Although we document some examples of directional hybridization, the patterns strongly support the hypothesis that llama (Lama glama) is derived from guanaco (Lama guanicoe) and the alpaca (Vicugna pacos) from vicuña (Vicugna vicugna). Within male guanacos we identified a haplogroup formed by three haplotypes with different geographical distributions, the northernmost of which (Peru and northern Chile) was also observed in llamas, supporting the commonly held hypothesis that llamas were domesticated from the northernmost populations of guanacos (L. g. cacilensis). Southern guanacos shared the other two haplotypes. A second haplogroup, consisting of two haplotypes, was mostly present in vicuñas and alpacas. However, Y‐chromosome variation did not distinguish the two subspecies of vicuñas.  相似文献   

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Background  

SRY is the pivotal gene initiating male sex determination in most mammals, but how its expression is regulated is still not understood. In this study we derived novel SRY 5' flanking genomic sequence data from bovine and caprine genomic BAC clones.  相似文献   

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Sex chromosomes have different evolutionary properties compared to autosomes due to their hemizygous nature. In particular, recessive mutations are more readily exposed to selection, which can lead to faster rates of molecular evolution. Here, we report patterns of gene expression and molecular evolution for a group of butterflies. First, we improve the completeness of the Heliconius melpomene reference annotation, a neotropical butterfly with a ZW sex determination system. Then, we analyse RNA from male and female whole abdomens and sequence female ovary and gut tissue to identify sex‐ and tissue‐specific gene expression profiles in H. melpomene. Using these expression profiles, we compare (a) sequence divergence and polymorphism; (b) the strength of positive and negative selection; and (c) rates of adaptive evolution, for Z and autosomal genes between two species of Heliconius butterflies, H. melpomene and H. erato. We show that the rate of adaptive substitutions is higher for Z than autosomal genes, but contrary to expectation, it is also higher for male‐biased than female‐biased genes. Additionally, we find no significant increase in the rate of adaptive evolution or purifying selection on genes expressed in ovary tissue, a heterogametic‐specific tissue. Our results contribute to a growing body of literature from other ZW systems that also provide mixed evidence for a fast‐Z effect where hemizygosity influences the rate of adaptive substitutions.  相似文献   

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Common DNA‐based sexing assays have been widely used for the conservation and management of mammals and birds. However, many fishes do not have genetic sex determination and in those that do, the plasticity of the genes involved means that species‐specific assays are normally required. Such DNA‐sexing markers would be especially valuable in lake sturgeon (Acipenser fulvescens) because of their sexual monomorphism, delayed sexual maturity, and conservation status. We tried to identify genetic differences between male and female lake sturgeon using several different molecular genetic methods, including randomly amplified polymorphic DNA, representational difference analyses, subtractive hybridization, and a candidate gene approach. Ultimately, a number of genes were identified but none was sex‐specific. Although the ultimate mechanism of sex determination is yet unknown, it is possible that sex determination is environmental in lake sturgeon, especially since recent studies have also failed to identify sex determination genes in other sturgeon species.  相似文献   

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Summary: R‐spondins are secreted ligands that bind cell surface receptors and activate Wnt/β‐catenin signaling. Human mutations and gene inactivation studies in mice have revealed a role for these four proteins (RSPO1‐4) in diverse developmental processes ranging from sex determination to limb development. Among the genes coding for R‐spondins, only inactivation of Rspo3 shows early embryonic lethality (E10.5 in mice). Therefore, a conditional allele of this gene is necessary to understand the function of R‐spondins throughout murine development. To address this need, we have produced an allele in which loxP sites flank exons 2–4 of Rspo3, allowing tissue‐specific deletion of these exons in the presence of Cre recombinase. We used these mice to investigate the role of Rspo3 during limb development and found that limbs ultimately developed normally in the absence of Rspo3 function. However, severe hindlimb truncations resulted when Rspo3 and Rspo2 mutations were combined, demonstrating redundant function of these genes. genesis 50:741–749, 2012. © 2012 Wiley Periodicals, Inc.  相似文献   

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Irregular menstrual cycles, reduced responses to exogenous hormonal treatments, and altered endocrine profiles (high FSH/high LH/low AMH) are observed in women with increasing age before menopause. In this study, because the granulosa cell‐specific Nrg1 knockout mice (gcNrg1KO) presented ovarian and endocrine phenotypes similar to older women, we sought to understand the mechanisms of ovarian aging and to develop a new strategy for improving fertility in older women prior to menopause. In the ovary of 6‐month‐old gcNrg1KO mice, follicular development was blocked in bilayer secondary follicles and heterogeneous cells accumulated in ovarian stroma. The heterogeneous cells in ovarian stroma were distinguished as two different types: (i) the LH receptor‐positive endocrine cells and (ii) actin‐rich fibrotic cells expressing collagen. Both the endocrine and fibrotic cells disappeared following long‐term treatment with a GnRH antagonist, indicating that the high levels of serum LH induced the survival of both cell types and the abnormal endocrine profile to reduce fertility. Moreover, follicular development to the antral stages was observed with reduced LH and the disappearance of the abnormal stromal cells. Mice treated with the GnRH antagonist regained normal, recurrent estrous cycles and continuously delivered pups for at least for 3 months. We conclude that endocrine and matrix alternations occur within the ovarian stroma with increasing age and that abolishing these alternations resets the cyclical release of LH. Thus, GnRH antagonist treatments might provide a new, noninvasive strategy for improving fertility in a subset of aging women before menopause.  相似文献   

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We report a Mexican family in which two sibs were identified as “classic” XX males without genital ambiguities. Molecular studies revealed that both patients were negative for several Y sequences, including SRY. A review of familial cases disclosed that this is the first family where a complete male phenotype was observed in Y-negative XX male non-twin brothers. These data suggest that an inherited loss-of-function mutation, in a gene participating in the sex-determining cascade, can induce normal male sexual differentiation in the absence of SRY. Received: 5 March 1997 / Accepted: 9 May 1997  相似文献   

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