斑马鱼Dmrt1和Dmrt5基因克隆和表达分析
|
摘要
许多生物的基本发育过程在进化地位不同物种间是相似的,而性别发育途径则不然,在物种间不具有保守性。虽然雌雄两性分化现象存在于整个动物界,但在不同物种间,其性别决定机制完全不同:包括哺乳动物的XY型性染色体类型,鸟类的ZW型性染色体类型,爬行类的温度依赖型性别决定机制等等。因此可知,相对其它重要的发育过程而言,性别决定机制的进化速度较快。Marin and Baker提出了另外一种假设,认为性别决定机制并不比其它发育过程变化更快,而是它们的变化更容易被鉴别。无论如何,这些多样性为研究发育调控网络的变化提供了极好的材料,当然,也增加了发现其起源的难度。
在目前研究基础上,产生一种新的假设:虽然性别发育相关基因进化较快,而控制系列的最下游的基因却可以是保守的。双性相关基因的发现,进一步肯定了这一推测。双性相关基因在不同物种中都参与了性别发育,例如,果蝇的doublesex,线虫的Mab-3,脊椎动物的Dmrt1/DMY基因等等。从线虫、果蝇直至哺乳类动物的性别发育过程中,这些双性相关基因是唯一相似的分子。它们编码一个潜在的转录因子,都含有一个共同的DNA结合区域,即DM域,因而又称为DM基因。果蝇DSX和线虫MAB-3控制其性别特异结构的分化,且在果蝇和线虫中功能上相关。Dmrt1基因在进化中保留了在性别发育中起作用的特点。人类DM基因,DMRT1,位于9号染色体短臂,而9p24的缺失与XY个体的性反转相关。该基因在性腺发育早期的雄性特异表达,与其在睾丸发育中的作用一致。小鼠Dmrt1基因的表达增高对睾丸分化是必须的,同时,低水平的表达与卵巢发育相关。Dmrt1敲除小鼠实验表明,该基因对性别决定后的睾丸分化是必须的,而对卵巢的发育没有影响。在其它几种脊椎动物中,也发现了Dmrt1基因的存在。鸡的Dmrt1基因是性别连锁的、位
Unlike many basic cellular processes shared across vast phylogenetic distances, sex-development pathways are highly variable between phyla. Despite morphologically distinct males and females are observed throughout the animal kingdom, Sex-determining mechanisms differ completely between phyla, including X- and Y-chromosome heterogametes in male mammals, Z- and W-chromosome heterogametes in female birds, and a temperature dependent sex determination in reptiles, etc. It is inferred that sex-determining mechanisms evolve rapidly, possibly more than other important developmental processes. But another hypothesis is proposed by Marin and Baker, sex determination mechanisms do not change more rapidly than other developmental processes, but rather that diversity in sex determination has been easier to identify. In any case, these varieties provide an excellent opportunity to study how the regulatory networks change, it also complicates the search for their origins.A hypothesis was put forward proposing that the genes involved in sex development process evolved rapidly and the most downstream genes in the cascade could be conserved, this predication has been supported by finding of doublesex-related genes which are widely conserved and involved in sexual development among phyla, e.g. doublesex (dsx) of Drosophila, mab-3 of Caenorhabditis elegans and DmrtllDMY of vertebrates. These DM domain genes, doublesex (dsx) (Drosophila), mab-3 (C. elegans) and Dmrtl (vertebrates), are the only similar molecule found in sexual development of metazoans from nematode, fly through to mammals. All these related genes have a common DNA-binding domain, termed the DM domain, which encode putative transcription factors. Both DSX and MAB-3 control the differentiation of sex specific structures and are
functionally related in both Drosophila and C. elegans. The Dmrtl retains still its characteristic in roles of sexual development in evolution. Human DM gene, DMRT1, is located on the short arm of chromosome 9. Deletions of this region of 9p24 are associated with XY sex reversal. Male-specific expression for the gene in early gonadogenesis is consistent with its role in testis development. In mouse, higher Dmrtl expression is necessary for testicular differentiation, whereas lower expression is compatible with ovarian differentiation. A Dmrtl knockout mouse demonstrated that the gene is required for testis differentiation after determination, but dispensable for ovary development. In several other vertebrates, Dmrtl genes have also been identified. In chicken, the Dmrtl is sex-linked, on the Z chromosome, and there is a higher dosage of the gene in the male as compared with the female. The homologs of the Dmrtl have also been cloned in turtle and alligator. The expression of Dmrtl was found to be sexually dimorphic in reptile species, and was stronger in embryos developing under male-specific temperature than in female ones. And the autosomal Dmrtl gene may have transposed to the Y chromosome and become a master regulator gene (Dmrtly/DMY) in male determination in some fish (medaka). These data show that the DM genes from invertebrates to vertebrates are sex-specific, often associated with male-specific development.The DM domain gene family has multiple members in both invertebrates and vertebrates. For example, Up to date, there are at least seven DM domain genes found in mouse, eight in human, four in Drosophila, eleven in C. elegans, and six in fish (Dmrt 1-5 and Dmrt2b), all of them encode putative transcription factors related to the sexual regulator Dsx of Drosophila and Mab-3 of C. elegans. Multiple DM domain genes have been suggested to be involved in mouse sexual development. At least three murine DM domain genes in addition to Dmrtl are expressed in the embryonic gonad, including Dmrt3, Dmrt4, and Dmrtl. However, Dmrt2 is expressed in presomitic mesoderm and developing somites, while DmrtS and Dmrt6 are expressed primarily in the brain, suggesting a role in other developing processes.Although some of the DM genes are involved in sexual development, function of most of these genes remains unclear, and we know remarkably little about the evolution of
the DM genes. It is still the question that the male-specific role of the DM genes is primordial during their evolution, or independently evolved by convergence. Furthermore, it is essential to understand the roles of the DM genes in regulatory pathway of sex determination, or if any, the roles in other developmental processes. There is also few structural and functional analysis concerning DM domain genes of the model fish, zebrafish, except terra/Dmrt2a, which was shown involving in process of somite development other than the sexual development. We report here cloning, characterization and expression of Dmrtl and Dmrt5 of zebrafish.In zebrafish, we identified five new Dmrt members by degenerate PCR amplification of DM domains, including Dmrtl, Dmrt2b, Dmrt3, Dmrt4 and Dmrt5. Zebrafish Dmrtl, Dmrt2, and Dmrt3 genes were shown to form a gene cluster, which was located on chromosome linkage group5 (LG5) of zebrafish. The synteny of these Dmrt genes was conserved in human, mouse, rat, fugu and medaka. The other DM domain genes in zebrafish are still waiting for identification.Based on the DNA sequence information, we designed primers for cloning full length Dmrtl. The cDNAs synthesized from SMART primer were used as template for both 5' RACE and 3' RACE by combined use of the primer pairs of DM domain and SMART primer. After both 5' and 3' half regions of Dmrtl sequence, which overlap in DM domain region, were obtained, full length Dmrtl sequence was amplified by PCR based on the 5' and 3' sequence information. Interestingly, there are at least three kinds of alternative splicing events in zebrafish gonads, which all occurred in the 3' region after the DM domain. Dmrtl al were a 138Obp full length cDNA encoding a predicted protein with 267 amino acids. In Dmrtl b, a deletion of the nucleotides CACACACA at nt 710 results in a frame shift with a different ORF of 242 or 254 amino acids (Dmrtl bl and Dmrtl b2). Dmrtl cl codes a potential protein with 132 amino acids. To get more information about the genomic structure of the Dmrtl, we searched the zebrafish (Danio rerio) Assembly database (Sanger Institute), and found the contig encoding the Dmrtl cDNAs. After compared the genomic sequence with mRNA sequences, we found that there were seven exons, which were alternatively spliced to generate the Dmrtl isoforms.
The Drosophila Dsx gene controls somatic sexual differentiation by producing alternatively-spliced mRNAs with different 3' region encoding related sex-specific protein DSXm in males and DSXf in females. Recently, we first observed the similar Dmrtl 3' splicing pattern with that of Drosophila Dsx, which generated three isoforms in gonads of the rice field eel, a fresh-water fish with sex transformation characteristic from female to male during its life. The alternative splicing was also observed in the Dmrtl of coral (Acropora millepora) and lizard {calotos versicolar). It appears likely that the alternatively splicing pattern of DM genes is evolutionarily conserved.All these zebrafish Dmrtl protein sequences were aligned with Drosophila DSX, C. elegans MAB-3, Dmrtl and DMY of the other fishes, turtle, frog, birds and mammals, which show conserved DM domain and diverse 3' and 5' regions. Another two conserved domains (domain I and II) in the 3' region were observed in both Dmrtl a and b, but not in Dmrtl c of zebrafish. We further constructed a phylogenetic tree based on amino acid sequences from all these DM proteins. These results show that the DM gene of zebrafish is clustered into the Dmrtl gene group of the other animals, and the DM proteins are evolutionarily conserved. An alignment of intron-exon junctions of Dmrtl of different species shows that intron-exon junctions of Dmrtl were conserved among phyla.To analyze the expression patterns of these spliced Dmrtls, we assayed their expression by RT-PCR using RNA isolated from adult gonads. All isoforms of the Dmrtls expression are detectable by RT-PCR in both male and female gonads of zebrafish. Quantitative RT-PCR analysis and Northern blotting further indicated that Dmrtl relative expression level in testis is higher than ovary. To determine expression region in gonads of zebrafish, we performed Dmrtl mRNA in situ hybridization to gonad sections. In zebrafish, expression pattern of the Dmrtl is quite different. Expression signals were observed in developing germ cells.Using same methods, we cloned the zebrafish DmrtS with full length of 1419bp, which consists of two exons, and encodes a 440-amino acid protein with conserved DMA and DMB domains in addition to DM domain. Phylogenetic analysis shows that zebrafish
DmrtS fits within the Dmrt5 clade of fish and mammals. Genome data do not show the exact information of location of DmrtS gene now, but data from pre-emsembl indicated that DmrtS gene maybe localized in LG8.Reverse transcription polymerase chain reaction (RT-PCR) analysis of total RNAs of different stages of embryos showed that DmrtS transcript appeared in early gastrula period, subsequently increased to a high level in late stage of gastrula period (bud stage) and lower until the hatch period. Quantitative RT-PCR analysis further indicated that relative expression level reached peak at stage 26-somites. Whole mount in situ hybridization was further used to analyze expression sites in embryos, which revealed that expression of zebrafish Dmrt5 was showed in central nervous system, specially in mid brain and mid-hind brain boundary.Reverse transcription polymerase chain reaction analysis of adult tissues showed that zebrafish DmrtS was specially expressed in brain, testis and ovary, but not in other tissues such as muscles, liver and intestine. Real time fluorescent quantitative RT-PCR was further used to determine expression level, which showed that expression is higher in testis than ovary. Clearly, this pattern of zebrafish DmrtS was quite distinct from that of human DMRTS. Expression of human DMRTS was only detected in adult testis. Although mouse DmrtS expression profiles of adult is not available, in 14.5 dpc embryos, it was expressed mainly in brain, testis and ovary, and expression were also detected in several other tissues. To examine expression sites in gonads of zebrafish Dmrt5, we further performed in situ hybridization to gonadal sections. Antisense probe for DmrtS showed expression in developing germ cells, especially in spermatogonia, spermatocytes, spermatids and sperm cells, and in ovary, its expression signals appeared in developing oocytes.
在目前研究基础上,产生一种新的假设:虽然性别发育相关基因进化较快,而控制系列的最下游的基因却可以是保守的。双性相关基因的发现,进一步肯定了这一推测。双性相关基因在不同物种中都参与了性别发育,例如,果蝇的doublesex,线虫的Mab-3,脊椎动物的Dmrt1/DMY基因等等。从线虫、果蝇直至哺乳类动物的性别发育过程中,这些双性相关基因是唯一相似的分子。它们编码一个潜在的转录因子,都含有一个共同的DNA结合区域,即DM域,因而又称为DM基因。果蝇DSX和线虫MAB-3控制其性别特异结构的分化,且在果蝇和线虫中功能上相关。Dmrt1基因在进化中保留了在性别发育中起作用的特点。人类DM基因,DMRT1,位于9号染色体短臂,而9p24的缺失与XY个体的性反转相关。该基因在性腺发育早期的雄性特异表达,与其在睾丸发育中的作用一致。小鼠Dmrt1基因的表达增高对睾丸分化是必须的,同时,低水平的表达与卵巢发育相关。Dmrt1敲除小鼠实验表明,该基因对性别决定后的睾丸分化是必须的,而对卵巢的发育没有影响。在其它几种脊椎动物中,也发现了Dmrt1基因的存在。鸡的Dmrt1基因是性别连锁的、位
Unlike many basic cellular processes shared across vast phylogenetic distances, sex-development pathways are highly variable between phyla. Despite morphologically distinct males and females are observed throughout the animal kingdom, Sex-determining mechanisms differ completely between phyla, including X- and Y-chromosome heterogametes in male mammals, Z- and W-chromosome heterogametes in female birds, and a temperature dependent sex determination in reptiles, etc. It is inferred that sex-determining mechanisms evolve rapidly, possibly more than other important developmental processes. But another hypothesis is proposed by Marin and Baker, sex determination mechanisms do not change more rapidly than other developmental processes, but rather that diversity in sex determination has been easier to identify. In any case, these varieties provide an excellent opportunity to study how the regulatory networks change, it also complicates the search for their origins.A hypothesis was put forward proposing that the genes involved in sex development process evolved rapidly and the most downstream genes in the cascade could be conserved, this predication has been supported by finding of doublesex-related genes which are widely conserved and involved in sexual development among phyla, e.g. doublesex (dsx) of Drosophila, mab-3 of Caenorhabditis elegans and DmrtllDMY of vertebrates. These DM domain genes, doublesex (dsx) (Drosophila), mab-3 (C. elegans) and Dmrtl (vertebrates), are the only similar molecule found in sexual development of metazoans from nematode, fly through to mammals. All these related genes have a common DNA-binding domain, termed the DM domain, which encode putative transcription factors. Both DSX and MAB-3 control the differentiation of sex specific structures and are
functionally related in both Drosophila and C. elegans. The Dmrtl retains still its characteristic in roles of sexual development in evolution. Human DM gene, DMRT1, is located on the short arm of chromosome 9. Deletions of this region of 9p24 are associated with XY sex reversal. Male-specific expression for the gene in early gonadogenesis is consistent with its role in testis development. In mouse, higher Dmrtl expression is necessary for testicular differentiation, whereas lower expression is compatible with ovarian differentiation. A Dmrtl knockout mouse demonstrated that the gene is required for testis differentiation after determination, but dispensable for ovary development. In several other vertebrates, Dmrtl genes have also been identified. In chicken, the Dmrtl is sex-linked, on the Z chromosome, and there is a higher dosage of the gene in the male as compared with the female. The homologs of the Dmrtl have also been cloned in turtle and alligator. The expression of Dmrtl was found to be sexually dimorphic in reptile species, and was stronger in embryos developing under male-specific temperature than in female ones. And the autosomal Dmrtl gene may have transposed to the Y chromosome and become a master regulator gene (Dmrtly/DMY) in male determination in some fish (medaka). These data show that the DM genes from invertebrates to vertebrates are sex-specific, often associated with male-specific development.The DM domain gene family has multiple members in both invertebrates and vertebrates. For example, Up to date, there are at least seven DM domain genes found in mouse, eight in human, four in Drosophila, eleven in C. elegans, and six in fish (Dmrt 1-5 and Dmrt2b), all of them encode putative transcription factors related to the sexual regulator Dsx of Drosophila and Mab-3 of C. elegans. Multiple DM domain genes have been suggested to be involved in mouse sexual development. At least three murine DM domain genes in addition to Dmrtl are expressed in the embryonic gonad, including Dmrt3, Dmrt4, and Dmrtl. However, Dmrt2 is expressed in presomitic mesoderm and developing somites, while DmrtS and Dmrt6 are expressed primarily in the brain, suggesting a role in other developing processes.Although some of the DM genes are involved in sexual development, function of most of these genes remains unclear, and we know remarkably little about the evolution of
the DM genes. It is still the question that the male-specific role of the DM genes is primordial during their evolution, or independently evolved by convergence. Furthermore, it is essential to understand the roles of the DM genes in regulatory pathway of sex determination, or if any, the roles in other developmental processes. There is also few structural and functional analysis concerning DM domain genes of the model fish, zebrafish, except terra/Dmrt2a, which was shown involving in process of somite development other than the sexual development. We report here cloning, characterization and expression of Dmrtl and Dmrt5 of zebrafish.In zebrafish, we identified five new Dmrt members by degenerate PCR amplification of DM domains, including Dmrtl, Dmrt2b, Dmrt3, Dmrt4 and Dmrt5. Zebrafish Dmrtl, Dmrt2, and Dmrt3 genes were shown to form a gene cluster, which was located on chromosome linkage group5 (LG5) of zebrafish. The synteny of these Dmrt genes was conserved in human, mouse, rat, fugu and medaka. The other DM domain genes in zebrafish are still waiting for identification.Based on the DNA sequence information, we designed primers for cloning full length Dmrtl. The cDNAs synthesized from SMART primer were used as template for both 5' RACE and 3' RACE by combined use of the primer pairs of DM domain and SMART primer. After both 5' and 3' half regions of Dmrtl sequence, which overlap in DM domain region, were obtained, full length Dmrtl sequence was amplified by PCR based on the 5' and 3' sequence information. Interestingly, there are at least three kinds of alternative splicing events in zebrafish gonads, which all occurred in the 3' region after the DM domain. Dmrtl al were a 138Obp full length cDNA encoding a predicted protein with 267 amino acids. In Dmrtl b, a deletion of the nucleotides CACACACA at nt 710 results in a frame shift with a different ORF of 242 or 254 amino acids (Dmrtl bl and Dmrtl b2). Dmrtl cl codes a potential protein with 132 amino acids. To get more information about the genomic structure of the Dmrtl, we searched the zebrafish (Danio rerio) Assembly database (Sanger Institute), and found the contig encoding the Dmrtl cDNAs. After compared the genomic sequence with mRNA sequences, we found that there were seven exons, which were alternatively spliced to generate the Dmrtl isoforms.
The Drosophila Dsx gene controls somatic sexual differentiation by producing alternatively-spliced mRNAs with different 3' region encoding related sex-specific protein DSXm in males and DSXf in females. Recently, we first observed the similar Dmrtl 3' splicing pattern with that of Drosophila Dsx, which generated three isoforms in gonads of the rice field eel, a fresh-water fish with sex transformation characteristic from female to male during its life. The alternative splicing was also observed in the Dmrtl of coral (Acropora millepora) and lizard {calotos versicolar). It appears likely that the alternatively splicing pattern of DM genes is evolutionarily conserved.All these zebrafish Dmrtl protein sequences were aligned with Drosophila DSX, C. elegans MAB-3, Dmrtl and DMY of the other fishes, turtle, frog, birds and mammals, which show conserved DM domain and diverse 3' and 5' regions. Another two conserved domains (domain I and II) in the 3' region were observed in both Dmrtl a and b, but not in Dmrtl c of zebrafish. We further constructed a phylogenetic tree based on amino acid sequences from all these DM proteins. These results show that the DM gene of zebrafish is clustered into the Dmrtl gene group of the other animals, and the DM proteins are evolutionarily conserved. An alignment of intron-exon junctions of Dmrtl of different species shows that intron-exon junctions of Dmrtl were conserved among phyla.To analyze the expression patterns of these spliced Dmrtls, we assayed their expression by RT-PCR using RNA isolated from adult gonads. All isoforms of the Dmrtls expression are detectable by RT-PCR in both male and female gonads of zebrafish. Quantitative RT-PCR analysis and Northern blotting further indicated that Dmrtl relative expression level in testis is higher than ovary. To determine expression region in gonads of zebrafish, we performed Dmrtl mRNA in situ hybridization to gonad sections. In zebrafish, expression pattern of the Dmrtl is quite different. Expression signals were observed in developing germ cells.Using same methods, we cloned the zebrafish DmrtS with full length of 1419bp, which consists of two exons, and encodes a 440-amino acid protein with conserved DMA and DMB domains in addition to DM domain. Phylogenetic analysis shows that zebrafish
DmrtS fits within the Dmrt5 clade of fish and mammals. Genome data do not show the exact information of location of DmrtS gene now, but data from pre-emsembl indicated that DmrtS gene maybe localized in LG8.Reverse transcription polymerase chain reaction (RT-PCR) analysis of total RNAs of different stages of embryos showed that DmrtS transcript appeared in early gastrula period, subsequently increased to a high level in late stage of gastrula period (bud stage) and lower until the hatch period. Quantitative RT-PCR analysis further indicated that relative expression level reached peak at stage 26-somites. Whole mount in situ hybridization was further used to analyze expression sites in embryos, which revealed that expression of zebrafish Dmrt5 was showed in central nervous system, specially in mid brain and mid-hind brain boundary.Reverse transcription polymerase chain reaction analysis of adult tissues showed that zebrafish DmrtS was specially expressed in brain, testis and ovary, but not in other tissues such as muscles, liver and intestine. Real time fluorescent quantitative RT-PCR was further used to determine expression level, which showed that expression is higher in testis than ovary. Clearly, this pattern of zebrafish DmrtS was quite distinct from that of human DMRTS. Expression of human DMRTS was only detected in adult testis. Although mouse DmrtS expression profiles of adult is not available, in 14.5 dpc embryos, it was expressed mainly in brain, testis and ovary, and expression were also detected in several other tissues. To examine expression sites in gonads of zebrafish Dmrt5, we further performed in situ hybridization to gonadal sections. Antisense probe for DmrtS showed expression in developing germ cells, especially in spermatogonia, spermatocytes, spermatids and sperm cells, and in ovary, its expression signals appeared in developing oocytes.
引文
(1) Eddy, S. R. Non-coding RNA genes and the modern RNA world. Nat Rev Genet (2001) 2, 919-929.
(2) Hanke, J., Brett, D., Zastrow, I., Aydin, A., Delbruck, S., Lehmann, G, Luft, F., Reich, J., and Bork, P. Alternative splicing of human genes: more the rule than the exception? Trends Genet (1999) 15, 389-390.
(3) Mironov, A. A., Fickett, J. W., and Gelfand, M. S. Frequent alternative splicing of human genes. Genome Res (1999) 9,1288-1293.
(4) de Souza, S. J., Camargo, A. A., Briones, M. R., Costa, F. F., Nagai, M. A., Verjovski-Almeida, S., Zago, M. A., Andrade, L. E., Carrer, H., El-Dorry, H. F., Espreafico, E. M., Habr-Gama, A., Giannella-Neto, D., Goldman, G H., Gruber, A., Hackel, C, Kimura, E. T., Maciel, R. M, Marie, S. K., Martins, E. A., Nobrega, M. P., Paco-Larson, M. L., Pardini, M. I., Pereira, G G, Pesquero, J. B., Rodrigues, V., Rogatto, S. R., da Silva, I. D., Sogayar, M. C, de Fatima Sonati, M., Tajara, E. H., Valentini, S. R., Acencio, M., Alberto, F. L., Amaral, M. E., Aneas, I., Bengtson, M. H., Carraro, D. M., Carvalho, A. F., Carvalho, L. H., Cerutti, J. M., Correa, M. L., Costa, M. C, Curcio, C, Gushiken, T., Ho, P. L., Kimura, E., Leite, L. C, Maia, G, Majumder, P., Marins, M., Matsukuma, A., Melo, A. S., Mestriner, C. A., Miracca, E. C, Miranda, D. C, Nascimento, A. N., Nobrega, F. G, Ojopi, E. P., Pandolfi, J. R., Pessoa, L. G, Rahal, P., Rainho, C. A., da Ros, N., de Sa, R. G, Sales, M. M., da Silva, N. P., Silva, T. C, da Silva, W., Jr., Simao, D. F., Sousa, J. F., Stecconi, D., Tsukumo, F., Valente, V., Zalcbeg, H., Brentani, R. R., Reis, F. L., Dias-Neto, E., and Simpson, A. J. Identification of human chromosome 22 transcribed sequences with ORF expressed sequence tags. Proc Natl Acad Sci USA (2000) 97,12690-12693.
(5) Dias Neto, E., Correa, R. G, Verjovski-Almeida, S., Briones, M. R., Nagai, M. A., da Silva, W., Jr., Zago, M. A., Bordin, S., Costa, F. R, Goldman, G H., Carvalho, A. R, Matsukuma, A., Baia, G S., Simpson, D. H., Brunstein, A., de Oliveira, P. S., Bucher, P., Jongeneel, C. V., O'Hare, M. J., Soares, R, Brentani, R. R., Reis, L. R, de Souza, S. J., and Simpson, A. J. Shotgun sequencing of the human transcriptome with ORF expressed sequence tags. Proc NatlAcad Sci USA (2000) 97, 3491-3496.
(6) Loughney, K., Kreber, R., and Ganetzky, B. Molecular analysis of the para locus, a sodium channel gene in Drosophila. Cell (1989) 58, 1143-1154.
(7) Thackeray, J. R., and Ganetzky, B. Conserved alternative splicing patterns and splicing signals in the Drosophila sodium channel gene para. Genetics (1995) 141, 203-214.
(8) Palladino, M. J., Keegan, L. P., O'Connell, M. A., and Reenan, R. A. dADAR, a Drosophila double-stranded RNA-specific adenosine deaminase is highly developmentally regulated and is itself a target for RNA editing. Rna (2000) 6, 1004-1018.
(9) Burtis, K. C, and Baker, B. S. Drosophila doublesex gene controls somatic sexual differentiation by producing alternatively spliced mRNAs encoding related sex-specific polypeptides. Cell (1989) 56, 997-1010.
(10) Reddy, J. C, and Licht, J. D. The WT1 Wilms' tumor suppressor gene: how much do we really know? Biochim Biophys Acta (1996) 1287,1-28.
(11) Sharma, P. M., Bowman, M., Madden, S. L., Rauscher, F. J., 3rd, and Sukumar, S. RNA editing in the Wilms' tumor susceptibility gene, WT1. Genes Dev (1994) 8,720-731.
(12) 周荣家。参与发育的基因家族。遗传(2001)23,86-88。
(13) Capel, B. The battle of the sexes. Mech Dev (2000) 92, 89-103.
(14) Marin, I., and Baker, B. S. The Evolutionary Dynamics of Sex Determination. Science (1998) 281, 1990-1994.
(15) Sinclair, A. H., Berta, P., Palmer, M. S., Hawkins, J. R., Griffiths, B. L., Smith, M. J., Foster, J. W., Frischauf, A. M., Lovell-Badge, R., and Goodfellow, P. N. A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature (1990) 346, 240-244.
(16) Gubbay, J., Collignon, J., Koopman, P., Capel, B., Economou, A., Munsterberg, A., Vivian, N., Goodfellow, P., and Lovell-Badge, R. A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes. Nature (1990) 346, 245-250.
(17) Koopman, P., Gubbay, J., Vivian, N., Goodfellow, P., and Lovell-Badge, R. Male development of chromosomally female mice transgenic for SRY. Nature (1991) 351,117-121.
(18) Berta, P., Hawkins, J. R., Sinclair, A. H., Taylor, A., Griffiths, B. L., Goodfellow, P. N., and Fellous, M. Genetic evidence equating SRY and the testis-determining factor. Nature (1990) 348, 448-450.
(19) Harley, V. R., Lovell-Badge, R., and Goodfellow, P. N. Definition of a consensus DNA binding site for SRY. Nucleic Acids Res (1994) 22, 1500-1501.
(20) Koopman, P. The genetics and biology of vertebrate sex determination. Cell (2001) 105, 843-847.
(21) Meeks, S. L., Buatti, J. M., Bouchet, L. G., Bova, F. J., Ryken, T. C., Pennington, E. C., Anderson, K. M., and Friedman, W. A. Ultrasound-guided extracranial radiosurgery: technique and application. Int J Radiat Oncol Biol Phys (2003) 55, 1092-1101.
(22) Morrish, B. C., and Sinclair, A. H. Vertebrate sex determination: many means to an end. Reproduction (2002) 124, 447-457.
(23) Just, W., Rau, W., Vogel, W., Akhverdian, M., Fredga, K., Graves, J. A., and Lyapunova, E. Absence of Sry in species of the vole Ellobins. Nat Genet (1995) 11,117-118.
(24) 余先觉,周敦,李渝成,李康,周密。中国淡水鱼类染色体。,(1989),第一版 ed.,科学出版社,pp Pages.
(25) Devlin, R. H., and Nagahama, Y. Sex determination and sex differentiation in fish: an overview of genetic, physiological, and environmental influences. Aquaculture (2002) 208, 191-364.
(26) 王德寿,吴天利,张耀光。鱼类性别决定及其机制的研究进展。西南师范大学学报(自然科学版)(2000)25,296-304。
(27) 刘建康,顾国彦。鳝鱼性别逆转时生殖腺组织的改变。中国水生生物学汇报(1951)2,85-109。
(28) Kagawa, H., Tanaka, H., Okuzawa, K., and Kobayashi, M. GTH Ⅱ but not GTH Ⅰ induces final maturation and the development of maturational competence of oocytes of red seabream in vitro. Gen Comp Endocrinol (1998) 112, 80-88.
(29) 刘凌云。BrdU处理的鱼类染色体高分辨G—带带型分析。遗传学报(1988)15,117-121。
(30) 常重杰,余其兴。大鳞副泥鳅ZZ/ZW型性别决定的细胞遗传学证据。遗传(1997)19,17-19。
(31) Duchac, B., Huber, F., Mueller, H., and Senn, D. Mating behaviour and cytogenetical aspects of sex-inversion in the fish Coris julis L. (Labridae, Teleostei). Experientia (1982) 38, 809-810.
(32) Yamamoto, T., and Kajishima, T. Sex hormone induction of sex reversal in the goldfish and evidence for male heterogamity. J Exp Zool (1968) 168, 215-221.
(33) Nanda, I., Schartl, M., Epplen, J. T., Feichtinger, W., and Schmid, M. Primitive sex chromosomes in poeciliid fishes harbor simple repetitive DNA sequences. J Exp Zool (1993) 265, 301-308.
(34) Cline, T. W., and Meyer, B. J. Vive la difference: males vs females in flies vs worms. Annu Rev Genet (1996) 30, 637-702.
(35) Dawes, H. E., Berlin, D. S., Lapidus, D. M., Nusbaum, C, Davis, T. L, and Meyer, B. J. Dosage compensation proteins targeted to X chromosomes by a determinant of hermaphrodite fate. Science (1999) 284,1800-1804.
(36) Zarkower, D. Establishing sexual dimorphism: conservation amidst diversity? Nature Rev. Genet. (2001) 2,175-185.
(37) Raymond, C. S., Shamu, C. E., Shen, M. M., Seifert, K. J., Hirsch, B., Hodgkin, J., and Zarkower, D. Evidence for evolutionary conservation of sex-determining genes. Nature (1998) 391, 691-695.
(38) Baker, B. S., and Wolfner, M. F. A molecular analysis of doublesex, a bifunctional gene that controls both male and female sexual differentiation in Drosophila melanogaster. Genes Dev (1988) 2, 477-489.
(39) Schutt, C, and Nothiger, R. Structure, function and evolution of sex-determining systems in Dipteran insects. Development (2000) 127, 667-677.
(40) Shen, M. M., and Hodgkin, J. mab-3, a gene required for sex-specific yolk protein expression and a male-specific lineage in C. elegans. Cell (1988) 54, 1019-1031.
(41) Raymond, C. S., Murphy, M. W., O'Sullivan, M. G, Bardwell, V. J., and Zarkower, D. Dmrt1, a gene related to worm and fly sexual regulators, is required for mammalian testis differentiation. Genes Dev (2000) 14, 2587-2595.
(42) Zhu, L., Wilken, J., Phillips, N. B., Narendra, U., Chan, G, Stratton, S. M., Kent, S. B., and Weiss, M. A. Sexual dimorphism in diverse metazoans is regulated by a novel class of intertwined zinc fingers. Genes Dev (2000) 14,1750-1764.
(43) Meng, A., Moore, B., Tang, H., Yuan, B., and Lin, S. A Drosophila doublesex-related gene, terra, is involved in somitogenesis in vertebrates. Development (1999) 126,1259-1268.
(44) Nanda, I., Shan, Z., Schartl, M., Burt, D. W., Koehler, M., Nothwang, H., Grutzner, E, Paton, I. R., Windsor, D., Dunn, I., Engel, W, Staeheli, P., Mizuno, S., Haaf, T, and Schmid, M. 300 million years of conserved synteny between chicken Z and human chromosome 9. Nat Genet (1999) 21, 258-259.
(45) Nanda, I., Zend-Ajusch, E., Shan, Z., Grutzner, E, Schartl, M., Burt, D. W, Koehler, M., Fowler, V. M., Goodwin, G, Schneider, W. J., Mizuno, S., Dechant, G, Haaf, T., and Schmid, M. Conserved synteny between the chicken Z sex chromosome and human chromosome 9 includes the male regulatory gene DMRT1: a comparative (re)view on avian sex determination. Cytogenet Cell Genet (2000) 89, 67-78.
(46) Nanda, I., Kondo, M, Hornung, U., Asakawa, S., Winkler, C, Shimizu, A., Shan, Z., Haaf, T., Shimizu, N., Shima, A., Schmid, M., and Schartl, M. A duplicated copy of DMRT1 in the sex-determining region of the Y chromosome of the medaka, Oryzias latipes. Proc Natl Acad Sci U SA (2002) 99, 11778-11783.
(47) Matsuda, M, Nagahama, Y, Shinomiya, A., Sato, T., Matsuda, C, Kobayashi, T, Morrey, C. E., Shibata, N., Asakawa, S., Shimizu, N., Hori, H., Hamaguchi, S., and Sakaizumi, M. DMY is a Y-specific DM-domain gene required for male development in the medaka fish. Nature (2002) 417, 559-563.
(48) Kondo, M., Nanda, I., Hornung, U., Asakawa, S., Shimizu, N., Mitani, H., Schmid, M., Shima, A., and Schartl, M. Absence of the candidate male sex-determining gene dmrtlb(Y) of medaka from other fish species. Curr Biol (2003) 13,416-420.
(49) Volff, J. N., Kondo, M., and Schartl, M. Medaka dmY/dmrt1Y is not the universal primary sex-determining gene in fish. Trends Genet (2003) 19, 196-199.
(50) Veith, A. M., Froschauer, A., Korting, C, Nanda, I., Hanel, R., Schmid, M., Schartl, M., and Volff, J. N. Cloning of the dmrt1 gene of Xiphophorus maculatus: dmY/dmrtlY is not the master sex-determining gene in the platyfish. Gene (2003) 317, 59-66.
(51) Teranishi, M., Shimada, Y, Hori, T, Nakabayashi, O., Kikuchi, T, Macleod, T., Pym, R., Sheldon, B., Solovei, I., Macgregor, H., and Mizuno, S. Transcripts of the MHM region on the chicken Z chromosome accumulate as non-coding RNA in the nucleus of female cells adjacent to the DMRT1 locus. Chromosome Res (2001) 9,147-165.
(52) Lang, G, Knop, K., Pamler, R., Liewald, F., and Forster, R. [What is the cost of vascular operations? A prospective cost analysis of conventional and combined endovascular interventions]. Chirurg (2002) 73,185-191; discussion 192-183.
(53) Cho, S., and Wensink, P. C. DNA binding by the male and female doublesex proteins of Drosophila melanogaster. J Biol Chem (1997) 272, 3185-3189.
(54) Chen, J. K., and Heckert, L. L. Dmrt1 expression is regulated by follicle-stimulating hormone and phorbol esters in postnatal Sertoli cells. Endocrinology (2001) 142, 1167-1178.
(55) Narendra, U., Zhu, L., Li, B., Wilken, J., and Weiss, M. A. Sex-specific gene regulation. The Doublesex DM motif is a bipartite DNA-binding domain. J Biol Chem (2002) 277, 43463-43473.
(56) Yi, W., and Zarkower, D. Similarity of DNA binding and transcriptional regulation by Caenorhabditis elegans MAB-3 and Drosophila melanogaster DSX suggests conservation of sex determining mechanisms. Development (1999) 126,873-881.
(57) Raymond, C. S., Kettlewell, J. R., Hirsch, B., Bardwell, V. J., and Zarkower, D. Expression of Dmrt1 in the genital ridge of mouse and chicken embryos suggests a role in vertebrate sexual development. Dev Biol (1999) 215, 208-220.
(58) Raymond, C. S., Parker, E. D., Kettlewell, J. R., Brown, L. G, Page, D. C, Kusz, K., Jaruzelska, J., Reinberg, Y., Flejter, W. L., Bardwell, V. J., Hirsch, B., and Zarkower, D. A region of human chromosome 9p required for testis development contains two genes related to known sexual regulators. Hum Mol Genet (1999) 8, 989-996.
(59) Smith, C. A., McClive, P. J., Western, P. S., Reed, K. J., and Sinclair, A. H. Conservation of a sex-determining gene. Nature (1999) 402,601-602.
(60) De Grandi, A., Calvari, V., Bertini, V., Bulfone, A., Peverali, G, Camerino, G, Borsani, G, and Guioli, S. The expression pattern of a mouse doublesex-related gene is consistent with a role in gonadal differentiation. Mech Dev (2000) 90, 323-326.
(61) Guan, G, Kobayashi, T., and Nagahama, Y. Sexually dimorphic expression of two types of DM (Doublesex/Mab-3)-domain genes in a teleost fish, the Tilapia (Oreochromis niloticus). Biochem Biophys Res Commun (2000) 272, 662-666.
(62) Kettlewell, J. R., Raymond, C. S., and Zarkower, D. Temperature-dependent expression of turtle Dmrtl prior to sexual differentiation. Genesis (2000) 26, 174-178.
(63) Marchand, O., Govoroun, M., D'Cotta, H., McMeel, O., Lareyre, J., Bernot, A., Laudet, V., and Guiguen, Y. DMRT1 expression during gonadal differentiation and spermatogenesis in the rainbow trout, Oncorhynchus mykiss. Biochim Biophys Acta (2000) 1493,180-187.
(64) Moniot, B., Berta, P., Scherer, G, Sudbeck, P., and Poulat, F. Male specific expression suggests role of DMRT1 in human sex determination. Mech Dev (2000) 91, 323-325.
(65) Shan, Z., Nanda, I., Wang, Y., Schmid, M., Vortkamp, A., and Haaf, T. Sex-specific expression of an evolutionarily conserved male regulatory gene, DMRT1, in birds. Cytogenet Cell Genet (2000) 89, 252-257.
(66) Ohbayashi, F., Suzuki, M. G, Mita, K., Okano, K., and Shimada, T. A homologue of the Drosophila doublesex gene is transcribed into sex-specific mRNA isoforms in the silkworm, Bombyx mori. Comp Biochem Physiol B Biochem Mol Biol (2001) 128, 145-158.
(67) Garrett-Engele, C. M., Siegal, M. L., Manoli, D. S., Williams, B. C, Li, H., and Baker, B. S. intersex, a gene required for female sexual development in Drosophila, is expressed in both sexes and functions together with doublesex to regulate terminal differentiation. Development (2002) 129, 4661-4675.
(68) Hodgkin, J. The remarkable ubiquity of DM domain factors as regulators of sexual phenotype: ancestry or aptitude? Genes Dev (2002) 16, 2322-2326.
(69) Shetty, S., Kirby, P., Zarkower, D., and Graves, J. A. DMRT1 in a ratite bird: evidence for a role in sex determination and discovery of a putative regulatory element. Cytogenet Genome Res (2002) 99, 245-251.
(70) Shibata, K., Takase, M., and Nakamura, M. The Dmrt1 expression in sex-reversed gonads of amphibians. Gen Comp Endocrinol (2002) 127, 232-241.
(71) Sreenivasulu, K., Ganesh, S., and Raman, R. Evolutionarily conserved, DMRT1, encodes alternatively spliced transcripts and shows dimorphic expression during gonadal differentiation in the lizard, Calotes versicolor. Gene Expr Patterns (2002) 2, 51-60.
(72) Torres Maldonado, L. C, Landa Piedra, A., Moreno Mendoza, N., Marmolejo Valencia, A., Meza Martinez, A., and Merchant Larios, H. Expression profiles of Dax1, Dmrt1, and Sox9 during temperature sex determination in gonads of the sea turtle Lepidochelys olivacea. Gen Comp Endocrinol (2002) 129, 20-26.
(73) Aoyama, S., Shibata, K., Tokunaga, S., Takase, M., Matsui, K., and Nakamura, M. Expression of Dmrtl protein in developing and in sex-reversed gonads of amphibians. Cytogenet Genome Res (2003) 101, 295-301.
(74) Miller, S. W., Hayward, D. C, Bunch, T. A., Miller, D. J., Ball, E. E., Bardwell, V. J., Zarkower, D., and Brower, D. L. A DM domain protein from a coral, Acropora millepora, homologous to proteins important for sex determination. Evol Dev (2003) 5, 251-258.
(75) 黄晓。双性基因家族及Dmrt1与黄鳝性反转分子机制的研究。(2001) 武汉大学,博士学位论文 文。
(76) Muroya, K., Okuyama, T., Goishi, K., Ogiso, Y., Fukuda, S., Kameyama, J., Sato, H., Suzuki, Y., Terasaki, H., Gomyo, H., Wakui, K., Fukushima, Y, and Ogata, T. Sex-determining gene(s) on distal 9p: clinical and molecular studies in six cases. J Clin Endocrinol Metab (2000) 85, 3094-3100.
(77) Ogata, T., Muroya, K., Ohashi, H., Mochizuki, H., Hasegawa, T., and Kaji, M. Female gonadal development in XX patients with distal 9p monosomy. Eur J Endocrinol (2001) 145, 613-617.
(78) Ottolenghi, C, Fellous, M., Barbieri, M., and McElreavey, K. Novel paralogy relations among human chromosomes support a link between the phylogeny of doublesex-related genes and the evolution of sex determination. Genomics (2002) 79, 333-343.
(79) Kim, S., Kettlewell, J. R., Anderson, R. C, Bardwell, V. J., and Zarkower, D. Sexually dimorphic expression of multiple doublesex-related genes in the embryonic mouse gonad. Gene Expr Patterns (2003) 3, 77-82.
(80) Baker, B. S., Burtis, K., Goralski, T., Mattox, W., and Nagoshi, R. Molecular genetic aspects of sex determination in Drosophila melanogaster. Genome (1989) 31,638-645.
(81) Erdman, S. E., and Burtis, K. C. The Drosophila doublesex proteins share a novel zinc finger related DNA binding domain. EmboJ (1993) 12,527-535.
(82) Calvari, V., Bertini, V., De Grandi, A., Peverali, G, Zuffardi, O., Ferguson-Smith, M., Knudtzon, J., Camerino, G, Borsani, G, and Guioli, S. A new submicroscopic deletion that refines the 9p region for sex reversal. Genomics (2000) 65, 203-212.
(83) Ottolenghi, C, and McElreavey, K. Deletions of 9p and the quest for a conserved mechanism of sex determination. Mol Genet Metab (2000) 71, 397-404.
(84) Ottolenghi, C, Veitia, R., Quintana-Murci, L., Torchard, D., Scapoli, L., Souleyreau-Therville, N., Beckmann, J., Fellous, M., and McElreavey, K. The region on 9p associated with 46,XY sex reversal contains several transcripts expressed in the urogenital system and a novel doublesex-related domain. Genomics (2000) 64, 170-178.
(85) Ottolenghi, C, Veitia, R., Barbieri, M., Fellous, M., and McElreavey, K. The human doublesex-related gene, DMRT2, is homologous to a gene involved in somitogenesis and encodes a potential bicistronic transcript. Genomics (2000) 64, 179-186.
(86) Smith, C. A., and Sinclair, A. H. Sex determination in the chicken embryo. J Exp Zool (2001) 290, 691-699.
(87) Oreal, E., Mazaud, S., Picard, J. Y, Magre, S., and Carre-Eusebe, D. Different patterns of anti-Mullerian hormone expression, as related to DMRT1, SF-1, WT1, GATA-4, Wnt-4, and Lhx9 expression, in the chick differentiating gonads. Dev Dyn (2002) 225,221-232.
(88) Murdock, C, and Wibbels, T. Expression of Dmrt1 in a turtle with temperature-dependent sex determination. Cytogenet Genome Res (2003) 101, 302-308.
(89) Pask, A. J., Behringer, R. R., and Renfree, M. B. Expression of DMRT1 in the mammalian ovary and testis--from marsupials to mice. Cytogenet Genome Res (2003) 101,229-236.
(90) Ohmuro-Matsuyama, Y, Matsuda, M., Kobayashi, T., Ikeuchi, T., and Nagahama, Y Expression of DMY and DMRT1 in various tissues of the medaka (Oryzias latipes) [corrected]. Zoolog Sci (2003) 20,1395-1398.
(91) Smith, C. A., Katz, M., and Sinclair, A. H. DMRT1 is upregulated in the gonads during female-to-male sex reversal in ZW chicken embryos. Biol Reprod (2003) 68,560-570.
(92) Winkler, C, Hornung, U., Kondo, M., Neuner, C, Duschl, J., Shima, A., and Schartl, M. Developmentally regulated and non-sex-specific expression of autosomal dmrt genes in embryos of the Medaka fish (Oryzias latipes). Mech Dev (2004) 121, 997-1005.
(93) Lei, N., and Heckert, L. L. Gata4 regulates testis expression of Dmrtl. Mol Cell Biol (2004) 24, 377-388.
(94) Lints, R., and Emmons, S. W. Regulation of sex-specific differentiation and mating behavior in C. elegans by a new member of the DM domain transcription factor family. Genes Dev (2002) 16, 2390-2402.
(95) Zhao, Z., Hua, Z., and Meng, A. Genomic organization and expression in E.coli of zebrafish terra. Tsinghua sci and tech (2001) 6,265-268.
(96) Guo, Y, Gao, S., Cheng, H., and Zhou, R. Phylogenetic Tree and Synteny of DMRT Genes Family of Vertebrates.Acta Genetica Sinica (2004) 31,1103-1108.
(97) Lutfalla, G, Roest Crollius, H., Brunet, F. G, Laudet, V., and Robinson-Rechavi, M. Inventing a sex-specific gene: a conserved role of DMRT1 in teleost fishes plus a recent duplication in the medaka Oryzias latipes resulted in DMY.J Mol Evol (2003)57 Suppl 1, S148-153.
(98) Koopman,P., and Loffler, K. A. Sex determination: the fishy tale of Dmrt1. Curr Biol (2003) 13, R177-179.
(99) Zhang, J. Evolution of DMY, a newly emergent male sex-determination gene of medaka fish. Genetics (2004) 166,1887-1895.
(2) Hanke, J., Brett, D., Zastrow, I., Aydin, A., Delbruck, S., Lehmann, G, Luft, F., Reich, J., and Bork, P. Alternative splicing of human genes: more the rule than the exception? Trends Genet (1999) 15, 389-390.
(3) Mironov, A. A., Fickett, J. W., and Gelfand, M. S. Frequent alternative splicing of human genes. Genome Res (1999) 9,1288-1293.
(4) de Souza, S. J., Camargo, A. A., Briones, M. R., Costa, F. F., Nagai, M. A., Verjovski-Almeida, S., Zago, M. A., Andrade, L. E., Carrer, H., El-Dorry, H. F., Espreafico, E. M., Habr-Gama, A., Giannella-Neto, D., Goldman, G H., Gruber, A., Hackel, C, Kimura, E. T., Maciel, R. M, Marie, S. K., Martins, E. A., Nobrega, M. P., Paco-Larson, M. L., Pardini, M. I., Pereira, G G, Pesquero, J. B., Rodrigues, V., Rogatto, S. R., da Silva, I. D., Sogayar, M. C, de Fatima Sonati, M., Tajara, E. H., Valentini, S. R., Acencio, M., Alberto, F. L., Amaral, M. E., Aneas, I., Bengtson, M. H., Carraro, D. M., Carvalho, A. F., Carvalho, L. H., Cerutti, J. M., Correa, M. L., Costa, M. C, Curcio, C, Gushiken, T., Ho, P. L., Kimura, E., Leite, L. C, Maia, G, Majumder, P., Marins, M., Matsukuma, A., Melo, A. S., Mestriner, C. A., Miracca, E. C, Miranda, D. C, Nascimento, A. N., Nobrega, F. G, Ojopi, E. P., Pandolfi, J. R., Pessoa, L. G, Rahal, P., Rainho, C. A., da Ros, N., de Sa, R. G, Sales, M. M., da Silva, N. P., Silva, T. C, da Silva, W., Jr., Simao, D. F., Sousa, J. F., Stecconi, D., Tsukumo, F., Valente, V., Zalcbeg, H., Brentani, R. R., Reis, F. L., Dias-Neto, E., and Simpson, A. J. Identification of human chromosome 22 transcribed sequences with ORF expressed sequence tags. Proc Natl Acad Sci USA (2000) 97,12690-12693.
(5) Dias Neto, E., Correa, R. G, Verjovski-Almeida, S., Briones, M. R., Nagai, M. A., da Silva, W., Jr., Zago, M. A., Bordin, S., Costa, F. R, Goldman, G H., Carvalho, A. R, Matsukuma, A., Baia, G S., Simpson, D. H., Brunstein, A., de Oliveira, P. S., Bucher, P., Jongeneel, C. V., O'Hare, M. J., Soares, R, Brentani, R. R., Reis, L. R, de Souza, S. J., and Simpson, A. J. Shotgun sequencing of the human transcriptome with ORF expressed sequence tags. Proc NatlAcad Sci USA (2000) 97, 3491-3496.
(6) Loughney, K., Kreber, R., and Ganetzky, B. Molecular analysis of the para locus, a sodium channel gene in Drosophila. Cell (1989) 58, 1143-1154.
(7) Thackeray, J. R., and Ganetzky, B. Conserved alternative splicing patterns and splicing signals in the Drosophila sodium channel gene para. Genetics (1995) 141, 203-214.
(8) Palladino, M. J., Keegan, L. P., O'Connell, M. A., and Reenan, R. A. dADAR, a Drosophila double-stranded RNA-specific adenosine deaminase is highly developmentally regulated and is itself a target for RNA editing. Rna (2000) 6, 1004-1018.
(9) Burtis, K. C, and Baker, B. S. Drosophila doublesex gene controls somatic sexual differentiation by producing alternatively spliced mRNAs encoding related sex-specific polypeptides. Cell (1989) 56, 997-1010.
(10) Reddy, J. C, and Licht, J. D. The WT1 Wilms' tumor suppressor gene: how much do we really know? Biochim Biophys Acta (1996) 1287,1-28.
(11) Sharma, P. M., Bowman, M., Madden, S. L., Rauscher, F. J., 3rd, and Sukumar, S. RNA editing in the Wilms' tumor susceptibility gene, WT1. Genes Dev (1994) 8,720-731.
(12) 周荣家。参与发育的基因家族。遗传(2001)23,86-88。
(13) Capel, B. The battle of the sexes. Mech Dev (2000) 92, 89-103.
(14) Marin, I., and Baker, B. S. The Evolutionary Dynamics of Sex Determination. Science (1998) 281, 1990-1994.
(15) Sinclair, A. H., Berta, P., Palmer, M. S., Hawkins, J. R., Griffiths, B. L., Smith, M. J., Foster, J. W., Frischauf, A. M., Lovell-Badge, R., and Goodfellow, P. N. A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature (1990) 346, 240-244.
(16) Gubbay, J., Collignon, J., Koopman, P., Capel, B., Economou, A., Munsterberg, A., Vivian, N., Goodfellow, P., and Lovell-Badge, R. A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes. Nature (1990) 346, 245-250.
(17) Koopman, P., Gubbay, J., Vivian, N., Goodfellow, P., and Lovell-Badge, R. Male development of chromosomally female mice transgenic for SRY. Nature (1991) 351,117-121.
(18) Berta, P., Hawkins, J. R., Sinclair, A. H., Taylor, A., Griffiths, B. L., Goodfellow, P. N., and Fellous, M. Genetic evidence equating SRY and the testis-determining factor. Nature (1990) 348, 448-450.
(19) Harley, V. R., Lovell-Badge, R., and Goodfellow, P. N. Definition of a consensus DNA binding site for SRY. Nucleic Acids Res (1994) 22, 1500-1501.
(20) Koopman, P. The genetics and biology of vertebrate sex determination. Cell (2001) 105, 843-847.
(21) Meeks, S. L., Buatti, J. M., Bouchet, L. G., Bova, F. J., Ryken, T. C., Pennington, E. C., Anderson, K. M., and Friedman, W. A. Ultrasound-guided extracranial radiosurgery: technique and application. Int J Radiat Oncol Biol Phys (2003) 55, 1092-1101.
(22) Morrish, B. C., and Sinclair, A. H. Vertebrate sex determination: many means to an end. Reproduction (2002) 124, 447-457.
(23) Just, W., Rau, W., Vogel, W., Akhverdian, M., Fredga, K., Graves, J. A., and Lyapunova, E. Absence of Sry in species of the vole Ellobins. Nat Genet (1995) 11,117-118.
(24) 余先觉,周敦,李渝成,李康,周密。中国淡水鱼类染色体。,(1989),第一版 ed.,科学出版社,pp Pages.
(25) Devlin, R. H., and Nagahama, Y. Sex determination and sex differentiation in fish: an overview of genetic, physiological, and environmental influences. Aquaculture (2002) 208, 191-364.
(26) 王德寿,吴天利,张耀光。鱼类性别决定及其机制的研究进展。西南师范大学学报(自然科学版)(2000)25,296-304。
(27) 刘建康,顾国彦。鳝鱼性别逆转时生殖腺组织的改变。中国水生生物学汇报(1951)2,85-109。
(28) Kagawa, H., Tanaka, H., Okuzawa, K., and Kobayashi, M. GTH Ⅱ but not GTH Ⅰ induces final maturation and the development of maturational competence of oocytes of red seabream in vitro. Gen Comp Endocrinol (1998) 112, 80-88.
(29) 刘凌云。BrdU处理的鱼类染色体高分辨G—带带型分析。遗传学报(1988)15,117-121。
(30) 常重杰,余其兴。大鳞副泥鳅ZZ/ZW型性别决定的细胞遗传学证据。遗传(1997)19,17-19。
(31) Duchac, B., Huber, F., Mueller, H., and Senn, D. Mating behaviour and cytogenetical aspects of sex-inversion in the fish Coris julis L. (Labridae, Teleostei). Experientia (1982) 38, 809-810.
(32) Yamamoto, T., and Kajishima, T. Sex hormone induction of sex reversal in the goldfish and evidence for male heterogamity. J Exp Zool (1968) 168, 215-221.
(33) Nanda, I., Schartl, M., Epplen, J. T., Feichtinger, W., and Schmid, M. Primitive sex chromosomes in poeciliid fishes harbor simple repetitive DNA sequences. J Exp Zool (1993) 265, 301-308.
(34) Cline, T. W., and Meyer, B. J. Vive la difference: males vs females in flies vs worms. Annu Rev Genet (1996) 30, 637-702.
(35) Dawes, H. E., Berlin, D. S., Lapidus, D. M., Nusbaum, C, Davis, T. L, and Meyer, B. J. Dosage compensation proteins targeted to X chromosomes by a determinant of hermaphrodite fate. Science (1999) 284,1800-1804.
(36) Zarkower, D. Establishing sexual dimorphism: conservation amidst diversity? Nature Rev. Genet. (2001) 2,175-185.
(37) Raymond, C. S., Shamu, C. E., Shen, M. M., Seifert, K. J., Hirsch, B., Hodgkin, J., and Zarkower, D. Evidence for evolutionary conservation of sex-determining genes. Nature (1998) 391, 691-695.
(38) Baker, B. S., and Wolfner, M. F. A molecular analysis of doublesex, a bifunctional gene that controls both male and female sexual differentiation in Drosophila melanogaster. Genes Dev (1988) 2, 477-489.
(39) Schutt, C, and Nothiger, R. Structure, function and evolution of sex-determining systems in Dipteran insects. Development (2000) 127, 667-677.
(40) Shen, M. M., and Hodgkin, J. mab-3, a gene required for sex-specific yolk protein expression and a male-specific lineage in C. elegans. Cell (1988) 54, 1019-1031.
(41) Raymond, C. S., Murphy, M. W., O'Sullivan, M. G, Bardwell, V. J., and Zarkower, D. Dmrt1, a gene related to worm and fly sexual regulators, is required for mammalian testis differentiation. Genes Dev (2000) 14, 2587-2595.
(42) Zhu, L., Wilken, J., Phillips, N. B., Narendra, U., Chan, G, Stratton, S. M., Kent, S. B., and Weiss, M. A. Sexual dimorphism in diverse metazoans is regulated by a novel class of intertwined zinc fingers. Genes Dev (2000) 14,1750-1764.
(43) Meng, A., Moore, B., Tang, H., Yuan, B., and Lin, S. A Drosophila doublesex-related gene, terra, is involved in somitogenesis in vertebrates. Development (1999) 126,1259-1268.
(44) Nanda, I., Shan, Z., Schartl, M., Burt, D. W., Koehler, M., Nothwang, H., Grutzner, E, Paton, I. R., Windsor, D., Dunn, I., Engel, W, Staeheli, P., Mizuno, S., Haaf, T, and Schmid, M. 300 million years of conserved synteny between chicken Z and human chromosome 9. Nat Genet (1999) 21, 258-259.
(45) Nanda, I., Zend-Ajusch, E., Shan, Z., Grutzner, E, Schartl, M., Burt, D. W, Koehler, M., Fowler, V. M., Goodwin, G, Schneider, W. J., Mizuno, S., Dechant, G, Haaf, T., and Schmid, M. Conserved synteny between the chicken Z sex chromosome and human chromosome 9 includes the male regulatory gene DMRT1: a comparative (re)view on avian sex determination. Cytogenet Cell Genet (2000) 89, 67-78.
(46) Nanda, I., Kondo, M, Hornung, U., Asakawa, S., Winkler, C, Shimizu, A., Shan, Z., Haaf, T., Shimizu, N., Shima, A., Schmid, M., and Schartl, M. A duplicated copy of DMRT1 in the sex-determining region of the Y chromosome of the medaka, Oryzias latipes. Proc Natl Acad Sci U SA (2002) 99, 11778-11783.
(47) Matsuda, M, Nagahama, Y, Shinomiya, A., Sato, T., Matsuda, C, Kobayashi, T, Morrey, C. E., Shibata, N., Asakawa, S., Shimizu, N., Hori, H., Hamaguchi, S., and Sakaizumi, M. DMY is a Y-specific DM-domain gene required for male development in the medaka fish. Nature (2002) 417, 559-563.
(48) Kondo, M., Nanda, I., Hornung, U., Asakawa, S., Shimizu, N., Mitani, H., Schmid, M., Shima, A., and Schartl, M. Absence of the candidate male sex-determining gene dmrtlb(Y) of medaka from other fish species. Curr Biol (2003) 13,416-420.
(49) Volff, J. N., Kondo, M., and Schartl, M. Medaka dmY/dmrt1Y is not the universal primary sex-determining gene in fish. Trends Genet (2003) 19, 196-199.
(50) Veith, A. M., Froschauer, A., Korting, C, Nanda, I., Hanel, R., Schmid, M., Schartl, M., and Volff, J. N. Cloning of the dmrt1 gene of Xiphophorus maculatus: dmY/dmrtlY is not the master sex-determining gene in the platyfish. Gene (2003) 317, 59-66.
(51) Teranishi, M., Shimada, Y, Hori, T, Nakabayashi, O., Kikuchi, T, Macleod, T., Pym, R., Sheldon, B., Solovei, I., Macgregor, H., and Mizuno, S. Transcripts of the MHM region on the chicken Z chromosome accumulate as non-coding RNA in the nucleus of female cells adjacent to the DMRT1 locus. Chromosome Res (2001) 9,147-165.
(52) Lang, G, Knop, K., Pamler, R., Liewald, F., and Forster, R. [What is the cost of vascular operations? A prospective cost analysis of conventional and combined endovascular interventions]. Chirurg (2002) 73,185-191; discussion 192-183.
(53) Cho, S., and Wensink, P. C. DNA binding by the male and female doublesex proteins of Drosophila melanogaster. J Biol Chem (1997) 272, 3185-3189.
(54) Chen, J. K., and Heckert, L. L. Dmrt1 expression is regulated by follicle-stimulating hormone and phorbol esters in postnatal Sertoli cells. Endocrinology (2001) 142, 1167-1178.
(55) Narendra, U., Zhu, L., Li, B., Wilken, J., and Weiss, M. A. Sex-specific gene regulation. The Doublesex DM motif is a bipartite DNA-binding domain. J Biol Chem (2002) 277, 43463-43473.
(56) Yi, W., and Zarkower, D. Similarity of DNA binding and transcriptional regulation by Caenorhabditis elegans MAB-3 and Drosophila melanogaster DSX suggests conservation of sex determining mechanisms. Development (1999) 126,873-881.
(57) Raymond, C. S., Kettlewell, J. R., Hirsch, B., Bardwell, V. J., and Zarkower, D. Expression of Dmrt1 in the genital ridge of mouse and chicken embryos suggests a role in vertebrate sexual development. Dev Biol (1999) 215, 208-220.
(58) Raymond, C. S., Parker, E. D., Kettlewell, J. R., Brown, L. G, Page, D. C, Kusz, K., Jaruzelska, J., Reinberg, Y., Flejter, W. L., Bardwell, V. J., Hirsch, B., and Zarkower, D. A region of human chromosome 9p required for testis development contains two genes related to known sexual regulators. Hum Mol Genet (1999) 8, 989-996.
(59) Smith, C. A., McClive, P. J., Western, P. S., Reed, K. J., and Sinclair, A. H. Conservation of a sex-determining gene. Nature (1999) 402,601-602.
(60) De Grandi, A., Calvari, V., Bertini, V., Bulfone, A., Peverali, G, Camerino, G, Borsani, G, and Guioli, S. The expression pattern of a mouse doublesex-related gene is consistent with a role in gonadal differentiation. Mech Dev (2000) 90, 323-326.
(61) Guan, G, Kobayashi, T., and Nagahama, Y. Sexually dimorphic expression of two types of DM (Doublesex/Mab-3)-domain genes in a teleost fish, the Tilapia (Oreochromis niloticus). Biochem Biophys Res Commun (2000) 272, 662-666.
(62) Kettlewell, J. R., Raymond, C. S., and Zarkower, D. Temperature-dependent expression of turtle Dmrtl prior to sexual differentiation. Genesis (2000) 26, 174-178.
(63) Marchand, O., Govoroun, M., D'Cotta, H., McMeel, O., Lareyre, J., Bernot, A., Laudet, V., and Guiguen, Y. DMRT1 expression during gonadal differentiation and spermatogenesis in the rainbow trout, Oncorhynchus mykiss. Biochim Biophys Acta (2000) 1493,180-187.
(64) Moniot, B., Berta, P., Scherer, G, Sudbeck, P., and Poulat, F. Male specific expression suggests role of DMRT1 in human sex determination. Mech Dev (2000) 91, 323-325.
(65) Shan, Z., Nanda, I., Wang, Y., Schmid, M., Vortkamp, A., and Haaf, T. Sex-specific expression of an evolutionarily conserved male regulatory gene, DMRT1, in birds. Cytogenet Cell Genet (2000) 89, 252-257.
(66) Ohbayashi, F., Suzuki, M. G, Mita, K., Okano, K., and Shimada, T. A homologue of the Drosophila doublesex gene is transcribed into sex-specific mRNA isoforms in the silkworm, Bombyx mori. Comp Biochem Physiol B Biochem Mol Biol (2001) 128, 145-158.
(67) Garrett-Engele, C. M., Siegal, M. L., Manoli, D. S., Williams, B. C, Li, H., and Baker, B. S. intersex, a gene required for female sexual development in Drosophila, is expressed in both sexes and functions together with doublesex to regulate terminal differentiation. Development (2002) 129, 4661-4675.
(68) Hodgkin, J. The remarkable ubiquity of DM domain factors as regulators of sexual phenotype: ancestry or aptitude? Genes Dev (2002) 16, 2322-2326.
(69) Shetty, S., Kirby, P., Zarkower, D., and Graves, J. A. DMRT1 in a ratite bird: evidence for a role in sex determination and discovery of a putative regulatory element. Cytogenet Genome Res (2002) 99, 245-251.
(70) Shibata, K., Takase, M., and Nakamura, M. The Dmrt1 expression in sex-reversed gonads of amphibians. Gen Comp Endocrinol (2002) 127, 232-241.
(71) Sreenivasulu, K., Ganesh, S., and Raman, R. Evolutionarily conserved, DMRT1, encodes alternatively spliced transcripts and shows dimorphic expression during gonadal differentiation in the lizard, Calotes versicolor. Gene Expr Patterns (2002) 2, 51-60.
(72) Torres Maldonado, L. C, Landa Piedra, A., Moreno Mendoza, N., Marmolejo Valencia, A., Meza Martinez, A., and Merchant Larios, H. Expression profiles of Dax1, Dmrt1, and Sox9 during temperature sex determination in gonads of the sea turtle Lepidochelys olivacea. Gen Comp Endocrinol (2002) 129, 20-26.
(73) Aoyama, S., Shibata, K., Tokunaga, S., Takase, M., Matsui, K., and Nakamura, M. Expression of Dmrtl protein in developing and in sex-reversed gonads of amphibians. Cytogenet Genome Res (2003) 101, 295-301.
(74) Miller, S. W., Hayward, D. C, Bunch, T. A., Miller, D. J., Ball, E. E., Bardwell, V. J., Zarkower, D., and Brower, D. L. A DM domain protein from a coral, Acropora millepora, homologous to proteins important for sex determination. Evol Dev (2003) 5, 251-258.
(75) 黄晓。双性基因家族及Dmrt1与黄鳝性反转分子机制的研究。(2001) 武汉大学,博士学位论文 文。
(76) Muroya, K., Okuyama, T., Goishi, K., Ogiso, Y., Fukuda, S., Kameyama, J., Sato, H., Suzuki, Y., Terasaki, H., Gomyo, H., Wakui, K., Fukushima, Y, and Ogata, T. Sex-determining gene(s) on distal 9p: clinical and molecular studies in six cases. J Clin Endocrinol Metab (2000) 85, 3094-3100.
(77) Ogata, T., Muroya, K., Ohashi, H., Mochizuki, H., Hasegawa, T., and Kaji, M. Female gonadal development in XX patients with distal 9p monosomy. Eur J Endocrinol (2001) 145, 613-617.
(78) Ottolenghi, C, Fellous, M., Barbieri, M., and McElreavey, K. Novel paralogy relations among human chromosomes support a link between the phylogeny of doublesex-related genes and the evolution of sex determination. Genomics (2002) 79, 333-343.
(79) Kim, S., Kettlewell, J. R., Anderson, R. C, Bardwell, V. J., and Zarkower, D. Sexually dimorphic expression of multiple doublesex-related genes in the embryonic mouse gonad. Gene Expr Patterns (2003) 3, 77-82.
(80) Baker, B. S., Burtis, K., Goralski, T., Mattox, W., and Nagoshi, R. Molecular genetic aspects of sex determination in Drosophila melanogaster. Genome (1989) 31,638-645.
(81) Erdman, S. E., and Burtis, K. C. The Drosophila doublesex proteins share a novel zinc finger related DNA binding domain. EmboJ (1993) 12,527-535.
(82) Calvari, V., Bertini, V., De Grandi, A., Peverali, G, Zuffardi, O., Ferguson-Smith, M., Knudtzon, J., Camerino, G, Borsani, G, and Guioli, S. A new submicroscopic deletion that refines the 9p region for sex reversal. Genomics (2000) 65, 203-212.
(83) Ottolenghi, C, and McElreavey, K. Deletions of 9p and the quest for a conserved mechanism of sex determination. Mol Genet Metab (2000) 71, 397-404.
(84) Ottolenghi, C, Veitia, R., Quintana-Murci, L., Torchard, D., Scapoli, L., Souleyreau-Therville, N., Beckmann, J., Fellous, M., and McElreavey, K. The region on 9p associated with 46,XY sex reversal contains several transcripts expressed in the urogenital system and a novel doublesex-related domain. Genomics (2000) 64, 170-178.
(85) Ottolenghi, C, Veitia, R., Barbieri, M., Fellous, M., and McElreavey, K. The human doublesex-related gene, DMRT2, is homologous to a gene involved in somitogenesis and encodes a potential bicistronic transcript. Genomics (2000) 64, 179-186.
(86) Smith, C. A., and Sinclair, A. H. Sex determination in the chicken embryo. J Exp Zool (2001) 290, 691-699.
(87) Oreal, E., Mazaud, S., Picard, J. Y, Magre, S., and Carre-Eusebe, D. Different patterns of anti-Mullerian hormone expression, as related to DMRT1, SF-1, WT1, GATA-4, Wnt-4, and Lhx9 expression, in the chick differentiating gonads. Dev Dyn (2002) 225,221-232.
(88) Murdock, C, and Wibbels, T. Expression of Dmrt1 in a turtle with temperature-dependent sex determination. Cytogenet Genome Res (2003) 101, 302-308.
(89) Pask, A. J., Behringer, R. R., and Renfree, M. B. Expression of DMRT1 in the mammalian ovary and testis--from marsupials to mice. Cytogenet Genome Res (2003) 101,229-236.
(90) Ohmuro-Matsuyama, Y, Matsuda, M., Kobayashi, T., Ikeuchi, T., and Nagahama, Y Expression of DMY and DMRT1 in various tissues of the medaka (Oryzias latipes) [corrected]. Zoolog Sci (2003) 20,1395-1398.
(91) Smith, C. A., Katz, M., and Sinclair, A. H. DMRT1 is upregulated in the gonads during female-to-male sex reversal in ZW chicken embryos. Biol Reprod (2003) 68,560-570.
(92) Winkler, C, Hornung, U., Kondo, M., Neuner, C, Duschl, J., Shima, A., and Schartl, M. Developmentally regulated and non-sex-specific expression of autosomal dmrt genes in embryos of the Medaka fish (Oryzias latipes). Mech Dev (2004) 121, 997-1005.
(93) Lei, N., and Heckert, L. L. Gata4 regulates testis expression of Dmrtl. Mol Cell Biol (2004) 24, 377-388.
(94) Lints, R., and Emmons, S. W. Regulation of sex-specific differentiation and mating behavior in C. elegans by a new member of the DM domain transcription factor family. Genes Dev (2002) 16, 2390-2402.
(95) Zhao, Z., Hua, Z., and Meng, A. Genomic organization and expression in E.coli of zebrafish terra. Tsinghua sci and tech (2001) 6,265-268.
(96) Guo, Y, Gao, S., Cheng, H., and Zhou, R. Phylogenetic Tree and Synteny of DMRT Genes Family of Vertebrates.Acta Genetica Sinica (2004) 31,1103-1108.
(97) Lutfalla, G, Roest Crollius, H., Brunet, F. G, Laudet, V., and Robinson-Rechavi, M. Inventing a sex-specific gene: a conserved role of DMRT1 in teleost fishes plus a recent duplication in the medaka Oryzias latipes resulted in DMY.J Mol Evol (2003)57 Suppl 1, S148-153.
(98) Koopman,P., and Loffler, K. A. Sex determination: the fishy tale of Dmrt1. Curr Biol (2003) 13, R177-179.
(99) Zhang, J. Evolution of DMY, a newly emergent male sex-determination gene of medaka fish. Genetics (2004) 166,1887-1895.