Primary sex determination: genetics and biochemistry

Summary On the basis of widespread phylogenetic conservatism, it has been propose'd that serologically-defined H-Y antigen is the inducer of primary sex differentiation in mammals, causing the initially indifferent gonad to become a testis rather than an ovary. The proposal has withstood extensive testing in a variety of biological circumstances: XX males have testes and are H-Y⁺ and fertile XY females lack testicular tissue and are H-Y; soluble H-Y antigen induces testicular organogenesis in XX indifferent gonads of the fetal calf in culture; H-Y antibody blocks tubular reaggregation of dispersed XY testicular cells, causing them to organize follicular clusters.There is a gonadal receptor for H-Y antigen: fetal ovarian cells that have been exposed to soluble H-Y (released for example by testicular Sertoli cells) take up the molecule and acquire the H-Y⁺ phenotype; they absorb H-Y antibody in serological tests. Specific uptake of soluble H-Y does not occur in the extra-gonadal tissues.It may be inferred that H-Y antigen is disseminated during embryogenesis and bound by specific receptors in cells of the primordial gonad, and that reaction of H-Y and its receptor signals a program of testicular differentiation, regardless of karyotype. The several anomalies of primary sexual differentiation manifest in such conditions as the XX male, the XX true hermaphrodite, and the XY female can thus reasonably be viewed as specific errors of synthesis, dissemination, and binding of H-Y antigen.H-Y is secreted by Daudi cells, cultured from a human XY Burkitt lymphoma. The Daudi-secreted moiety is a single hydrophobic protein of 18,000 molecular weight. Early attempts to characterize H-Y secreted by testicular Sertoli cells have yielded two molecules, one of 16,500 MW (corresponding to the Daudi-secreted 18,000 MW protein), and one of 31,000 MW. It remains to be ascertained whether both are in fact H-Y antigens, and if so, whether one is a polymer of the other, or whether each represents the product of genes with discrete testis-determining functions.     

Evolutionary genetics: changed sex determination in honeybees

In several insects and fish, and probably some mammals, the gene controlling the male-female switch has changed during evolution. It now seems that this has also happened in honeybees, where the sex-determining gene has now been shown to be a duplicate of another Hymenopteran sex-determining gene.     

Recent developments in the molecular genetics and biology of self-incompatibility

A summary of recent work on molecular aspects of self-incompatibility in Nicotiana alata is presented. The amino acid sequences of style proteins corresponding to different S-alleles of N. alata have a high level of homology in some regions and are variable in other regions. The regions of homology include N-terminal sequences as well as most of the glycosylation sites and cysteine residues. The glycosyl substituents may consist of a number of glycoforms. The isolated style S-glycoproteins inhibit in vitro growth of pollen tubes. The S-glycoproteins tested inhibited the growth of pollen of several S-genotypes, and there was some specificity in the interaction. Heat treatment of the isolated S-glycoproteins dramatically increased their activity as inhibitors of pollen tube growth, although the specificity in the interaction was lost. The nature of the S-allele products in pollen is not yet established.     

Sry: the master switch in mammalian sex determination

SRY, the mammalian Y-chromosomal testis-determining gene, induces male sex determination. Recent studies in mice reveal that the major role of SRY is to achieve sufficient expression of the related gene Sox9, in order to induce Sertoli cell differentiation, which in turn drives testis formation. Here, we discuss the cascade of events triggered by SRY and the mechanisms that reinforce the differentiation of the testes in males while actively inhibiting ovarian development.     

Semi-synthetic minimal cells: origin and recent developments

Semi-synthetic minimal cells are constructed by encapsulating the minimal number of nucleic acids, enzymes and low molecular-weight compounds inside lipid vesicles (liposomes) in order to create a cell-like system.

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Highlights► Minimal synthetic cells are used in origin of life studies and synthetic biology. ► The semi-synthetic approach is based on cell-free and liposome technology. ► Solutes can be super-encapsulated inside vesicles against the expectations. ► There have been new attempts to construct self-reproducing synthetic cells. ► Vesicle fusion and vesicle colonies emphasize the importance of cooperation.     

Comparative genetics of sex determination: masculinizing mutations in Caenorhabditis briggsae

The nematodes Caenorhabditis elegans and C. briggsae independently evolved self-fertile hermaphroditism from gonochoristic ancestors. C. briggsae has variably divergent orthologs of nearly all genes in the C. elegans sex determination pathway. Their functional characterization has generally relied on reverse genetic approaches, such as RNA interference and cross-species transgene rescue and more recently on deletion mutations. We have taken an unbiased forward mutagenesis approach to isolating zygotic mutations that masculinize all tissues of C. briggsae hermaphrodites. The screens identified loss-of-function mutations in the C. briggsae orthologs of tra-1, tra-2, and tra-3. The somatic and germline phenotypes of these mutations are largely identical to those of their C. elegans homologs, including the poorly understood germline feminization of tra-1(lf) males. This overall conservation of Cb-tra phenotypes is in contrast to the fem genes, with which they directly interact and which are significantly divergent in germline function. In addition, we show that in both C. briggsae and C. elegans large C-terminal truncations of TRA-1 that retain the DNA-binding domain affect sex determination more strongly than somatic gonad development. Beyond these immediate results, this collection of mutations provides an essential foundation for further comparative genetic analysis of the Caenorhabditis sex determination pathway.     

Genetics of mammalian sex determination: some unloved exceptions

The genetics of sex determination is a child of the twentieth century, which overturned the previously held view that sex was determined by the environment. The last quarter of the century witnessed an active search for sex-determining genes in mammals. Although successful, the modus operandi of these genes remained unknown, and the relationship between the sex-determining systems of mammals and other vertebrates remained enigmatic. To overcome these problems, scientists in the 21st century should heed William Bateson's counsel to treasure exceptions, for they point the way to progress. One exception to conventional concepts of sex determination is the bilaterally asymmetrical distribution of ovaries and testes in true hermaphroditism. Ovaries favour the left side in humans and the right side in mice. Observations suggesting that a reversal of asymmetry may occur with increasing organ size may point to a possible explanation. A reevaluation is also required regarding the beginning of sex differentiation, in view of mounting evidence of a sex difference in growth rates of early embryos. Another question to be settled is whether the function of SRY is confined to the fetal gonad. The recent demonstration that Sry induces cell proliferation in the fetal mouse gonad (Schmahl et al., 2000) further emphasizes the importance of differential growth in sex determination and differentiation. It is suggested that SRY represents an additional growth-promoting gene sequestered by mammals to enable the XY embryo to undergo male sex differentiation in the female hormonal environment of the uterus. An increased awareness of the relationship between growth and gonadal differentiation should lead to a better understanding of sex determination in mammals and an ability to relate the function of sex-determining genes to the effects of environmental factors. J. Exp. Zool. 290:484-489, 2001.     

Some recent developments in the molecular epidemiology of Epstein-Barr virus infections

We have applied two different recombinant DNA techniques to the study of the epidemiology of Epstein-Barr virus infections. In the first application, cloned subfragments of viral DNA were used as probes to detect EBV DNA in a variety of lymphoproliferative disorders and in lymphoid cell lines. Patients who are epidemiologically unrelated harbor EBV genotypes which can readily be distinguished from each other. Patients who are epidemiologically related (such as mothers and infants) have similar EBV genotypes. Some patients, especially those who are immunocompromised, are infected with two distinct genotypes. In the second application, we have examined the immune response to specific EBV antigens expressed from small cloned viral DNA subfragments. We have identified a group of patients with presumed chronic EBV infection who selectively fail to recognize one subcomponent of the EB nuclear antigen complex.     

Role of mammalian Y chromosome in sex determination

It has long been assumed that the mammalian Y chromosome either encodes, or controls the production of, a diffusible testis-determining molecule, exposure of the embryonic gonad to this molecule being all that is required to divert it along the testicular pathway. My recent finding that Sertoli cells in XX----XY chimeric mouse testes are exclusively XY has led me to propose a new model in which the Y acts cell-autonomously to bring about Sertoli-cell differentiation. I have suggested that all other aspects of foetal testicular development are triggered by the Sertoli cells without further Y-chromosome involvement. This model thus equates mammalian sex determination with Sertoli-cell determination. Examples of natural and experimentally induced sex reversal are discussed in the context of this model.     

Autosomal genes involved in mammalian primary sex determination

Beginning with findings made during the late 1950s and early 1960s, evidence continues to accumulate in support of the hypothesis that the mammalian Y chromosome carries a gene that induces the undifferentiated foetal gonad in XY individuals to develop as a testis. Recently a DNA sequence has been isolated from the human Y chromosome that appears to be the hypothesized Y-linked testis-determining gene, and advances have also been made toward identifying genes that interact with the Y-linked testis-determining (Tdy) gene to initiate testis formation. These loci have been identified in specific stocks of mice carrying the mutant Thp or TOrl allele at the T locus located on chromosome 17, and in crosses involving the transfer of a Y chromosome from two populations of Mus domesticus into the genomes of specific inbred strains of mice. The data in both cases support the hypothesis that there are several loci involved in testis determination and that abnormal interaction of these loci disrupts initiation of testis determination, resulting in development of ovarian tissue in XY individuals.     

遗传学教学中性别决定关键基因的阐述

有性生殖的出现是生物进化中的重大事件。性别作为生物的一种重要而又复杂的表型, 由基因和环境因素共同控制, 其中遗传因素即基因起到非常关键的作用。 然而, 并不是每个相关基因对于生物的性别都具有相同的作用, 性别决定关键基因对生物性别的决定和性别的分化具有重要作用, 因而研究和理解性别决定的关键基因具有重要意义。随着现代遗传学的发展, 目前关于生物性别决定方式以及性别决定关键基因的研究已取得了很大的进展。文章就生物的基因性别决定机制以及基因性别决定机制的研究策略进行了综述, 以期在遗传学教学中能更好地理解和阐述。