翻译调控序列的退化性突变及其对重复拷贝亚功能化的影响
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摘要
随着越来越多物种全基因组序列的测定,基因组的结构、组织和进化也开始揭开其神秘的面纱。对目前已知的多个物种基因组全序列的研究表明,所有的脊椎动物,尽管它们在整体水平上是二倍体,但它们的基因组中却存在着大量的重复基因。最近的研究表明,转录调控元件和蛋白结构域的互补性丢失可以使重复基因拷贝被保留,这些结果都有力地支持了加倍—退化—互补模型(DDC model)。但翻译调控区的序列变化能否对重复基因的命运产生影响并不是很清楚。在本研究中,我们通过对还处于恢复二倍化过程中的金鱼的vsxl(visual system homeobox-1)基因5’侧翼序列的克隆和分析,确定了该基因的拷贝数目,进一步分析了不同拷贝的表达、功能和组织特异性翻译差异,以为基因组加倍后重复基因拷贝被保留的分子机制提供新的线索。
本研究的主要研究结果和结论如下：
1.克隆了金鱼vsxlA2的全长mRNA序列,确定了其基因组结构,证明了vsx1A2和vsxlAl都是在基因组加倍后通过亚功能化而保留下来的两个有功能的vsxl基因座位。
2.将金鱼vsx1Al和vsx1A2的近端启动子区域与斑马鱼及人类vsxl基因对应的转录调控区域进行序列比对分析,发现在vsxl重复拷贝的转录调控区发生了调控元件的互补性丢失。基因表达分析结果显示vsxlAl和vsxlA2的表达时间既不相同,又有重叠。vsxlA2在原肠期胚胎有较高水平的转录,在体节期胚胎中的转录水平很低,而vsxlAl在胚胎发育早期的转录水平很低,在体节期胚胎中开始有较高水平的转录；在成体视网膜中vsxlAl和vsx1A2都能被转录,但vsxlAl的转录水平显著高于vsxlA2的转录水平。基因功能分析表明vsxlA2具有比vsxlAl更强的胚胎早期发育调控活性。
3.将金鱼vsxlAl和vsxlA2的翻译调控区(3’UTR)与斑马鱼及人类vsxl基因对应的3’UTR区域进行序列比对分析证明在3’UTR区域也发生了翻译调控元件的互补性丢失。通过构建包含vsxlAl和vsxlA2翻译调控区(3’UTR)的绿色荧光蛋白载体,对绿色荧光蛋白在不同发育时期胚胎中的表达模式进行检测,我们发现在孵育期及其以后发育时期的金鱼胚胎中,vsxlAl 3’UTR能够特异性地介导绿色荧光蛋白在视网膜中翻译,而vsxlA2 3’UTR已经失去了这种组织特异性翻译介导能力,提示vsxlA1在神经视网膜的发育调节中起更重要的作用。
这些研究结果说明：(1)vsx1基因在基因组加倍后通过亚功能化而使重复拷贝得以在基因组中保存；(2)亚功能化是通过转录调控区域和翻译调控区域调控元件的互补性丢失,造成vsxlAl和vsxlA2在表达时空上的区隔和互补而实现的；(3)在vsx1的亚功能化过程中,转录调控元件和翻译调控元件的互补性丢失,以及转录调控区和翻译调控区的协调变化都对重复基因拷贝通过亚功能化而保留和分享原vsxl基因的不同发育功能是必须的。我们的研究结果使DDC模型得到了更进一步的拓展和完善。
With the sequencing of entire genomes from various model organisms, the mysteries of genome structure, organization and evolution are beginning to be unveiled. Studies on the available whole-genome sequences revealed that, all vertebrates, despite their generally diploid state, have a lot of duplicated genes in their genomes. Recent studies support the duplication, degeneration, complementation (DDC) model of genome evolution through whole genome duplication by providing evidences that both complementary loss of transcription regulatory elements and peptide domains of the ancestral gene lead to preservation of duplicate genes. However, whether sequence divergence in translation regulatory region has impact on the preservation of duplicate genes remains unclear. Here, we choose goldfish, an ancient polyploidy animal which might be in the process of diploidization, as our research object. By cloning and analyzing the 5'flanking sequence of goldfish vsxl, we identified two vsxl gene loci in the goldfish genome, which were named vsx1A1 and vsx1A2 respectively. We further studied the expression patterns, function and tissue-specific translation of the goldfish vsx1 duplicates. Our results might add new clues to the molecular mechanism underlying the diploidization of the duplicated genes after the genome duplication.
The main results and conclusions of this research are as follows:
1. We cloned the full-length mRNA of goldfish vsx1A2 and identified its genomic structure. We further proved that both vsx1A1 and vsx1A2 were functional loci, they were retained in the goldfish genome by subfunctionalization and they shared the two different regulatory functions of acient vsxl.
2. By comparing the proximal promoter regions of goldfish vsx1A1 and vsx1A2 with the cognate regions of zebrafish and human vsxl, we found that complementary loss of regulatory sequences occurred at the transcription regulatory regions of the duplicate vsxl loci. Expression analysis showed that vsx1A1 and vsx1A2 were transcribed at overlapping and distinct developmental stages, vsx1A2 initiates transcription at gastrula stage and its transcription level was very low in segmentation stage embryos, while the transcription level of vsx1A1 was very low at early developmental stages embryos and much higher than vsx1A2 at segmentation stage embryos. Both vsx1A1 and vsx1A2 could be transcriped in the adult retina and the transcription level of vsx1A1 was significantly higher than vsx1A2. Gene function analysis indicated that vsx1A2 had much higher regulatory activity than vsx1A1 during early developmental stages.
3. By comparing the translation regulatory regions(3'UTR) of goldfish vsx1A1 and vsx1A2 with the cognate regions of zebrafish and human vsxl, we found that complementary loss of regulatory sequences also occurred at the translation regulatory regions of the duplicate vsxl loci. By constructing vsx1A1 or vsx1A2 3'UTR-1 inked Green Fluorescent Protein (GFP) reporter gene sensors and examining the GFP expression pattern in goldfish during different developmental stages, we demonstrated that vsx1A1 3'UTR can mediate retina-specific translation after hatching stage but vsx1A2 3'UTR has lost this translation mediating capability, suggesting that vsx1A1 might play a more important role in regulating retina development.
These results indicate that (1) after genome duplication, the goldfish vsxl duplicates were retained by subfunctionalization;(2)the subfunctionalization of the goldfish vsxl duplicates were accomplished by complementary loss of both transcription and translation regulatory elements, which resulted in the different spatio-temporal expression patterns of vsxlAl and vsx1A2; (3) Both the complementary loss of transcription and translation regulatory elements and the intergenic synergetic divergences at transcription and translation regulatory regions of the duplicate vsxl genes are essential for the preserving of the vsxl duplicates and the partitioning of the developmental functions of ancestral vsxl.
本研究的主要研究结果和结论如下：
1.克隆了金鱼vsxlA2的全长mRNA序列,确定了其基因组结构,证明了vsx1A2和vsxlAl都是在基因组加倍后通过亚功能化而保留下来的两个有功能的vsxl基因座位。
2.将金鱼vsx1Al和vsx1A2的近端启动子区域与斑马鱼及人类vsxl基因对应的转录调控区域进行序列比对分析,发现在vsxl重复拷贝的转录调控区发生了调控元件的互补性丢失。基因表达分析结果显示vsxlAl和vsxlA2的表达时间既不相同,又有重叠。vsxlA2在原肠期胚胎有较高水平的转录,在体节期胚胎中的转录水平很低,而vsxlAl在胚胎发育早期的转录水平很低,在体节期胚胎中开始有较高水平的转录；在成体视网膜中vsxlAl和vsx1A2都能被转录,但vsxlAl的转录水平显著高于vsxlA2的转录水平。基因功能分析表明vsxlA2具有比vsxlAl更强的胚胎早期发育调控活性。
3.将金鱼vsxlAl和vsxlA2的翻译调控区(3’UTR)与斑马鱼及人类vsxl基因对应的3’UTR区域进行序列比对分析证明在3’UTR区域也发生了翻译调控元件的互补性丢失。通过构建包含vsxlAl和vsxlA2翻译调控区(3’UTR)的绿色荧光蛋白载体,对绿色荧光蛋白在不同发育时期胚胎中的表达模式进行检测,我们发现在孵育期及其以后发育时期的金鱼胚胎中,vsxlAl 3’UTR能够特异性地介导绿色荧光蛋白在视网膜中翻译,而vsxlA2 3’UTR已经失去了这种组织特异性翻译介导能力,提示vsxlA1在神经视网膜的发育调节中起更重要的作用。
这些研究结果说明：(1)vsx1基因在基因组加倍后通过亚功能化而使重复拷贝得以在基因组中保存；(2)亚功能化是通过转录调控区域和翻译调控区域调控元件的互补性丢失,造成vsxlAl和vsxlA2在表达时空上的区隔和互补而实现的；(3)在vsx1的亚功能化过程中,转录调控元件和翻译调控元件的互补性丢失,以及转录调控区和翻译调控区的协调变化都对重复基因拷贝通过亚功能化而保留和分享原vsxl基因的不同发育功能是必须的。我们的研究结果使DDC模型得到了更进一步的拓展和完善。
With the sequencing of entire genomes from various model organisms, the mysteries of genome structure, organization and evolution are beginning to be unveiled. Studies on the available whole-genome sequences revealed that, all vertebrates, despite their generally diploid state, have a lot of duplicated genes in their genomes. Recent studies support the duplication, degeneration, complementation (DDC) model of genome evolution through whole genome duplication by providing evidences that both complementary loss of transcription regulatory elements and peptide domains of the ancestral gene lead to preservation of duplicate genes. However, whether sequence divergence in translation regulatory region has impact on the preservation of duplicate genes remains unclear. Here, we choose goldfish, an ancient polyploidy animal which might be in the process of diploidization, as our research object. By cloning and analyzing the 5'flanking sequence of goldfish vsxl, we identified two vsxl gene loci in the goldfish genome, which were named vsx1A1 and vsx1A2 respectively. We further studied the expression patterns, function and tissue-specific translation of the goldfish vsx1 duplicates. Our results might add new clues to the molecular mechanism underlying the diploidization of the duplicated genes after the genome duplication.
The main results and conclusions of this research are as follows:
1. We cloned the full-length mRNA of goldfish vsx1A2 and identified its genomic structure. We further proved that both vsx1A1 and vsx1A2 were functional loci, they were retained in the goldfish genome by subfunctionalization and they shared the two different regulatory functions of acient vsxl.
2. By comparing the proximal promoter regions of goldfish vsx1A1 and vsx1A2 with the cognate regions of zebrafish and human vsxl, we found that complementary loss of regulatory sequences occurred at the transcription regulatory regions of the duplicate vsxl loci. Expression analysis showed that vsx1A1 and vsx1A2 were transcribed at overlapping and distinct developmental stages, vsx1A2 initiates transcription at gastrula stage and its transcription level was very low in segmentation stage embryos, while the transcription level of vsx1A1 was very low at early developmental stages embryos and much higher than vsx1A2 at segmentation stage embryos. Both vsx1A1 and vsx1A2 could be transcriped in the adult retina and the transcription level of vsx1A1 was significantly higher than vsx1A2. Gene function analysis indicated that vsx1A2 had much higher regulatory activity than vsx1A1 during early developmental stages.
3. By comparing the translation regulatory regions(3'UTR) of goldfish vsx1A1 and vsx1A2 with the cognate regions of zebrafish and human vsxl, we found that complementary loss of regulatory sequences also occurred at the translation regulatory regions of the duplicate vsxl loci. By constructing vsx1A1 or vsx1A2 3'UTR-1 inked Green Fluorescent Protein (GFP) reporter gene sensors and examining the GFP expression pattern in goldfish during different developmental stages, we demonstrated that vsx1A1 3'UTR can mediate retina-specific translation after hatching stage but vsx1A2 3'UTR has lost this translation mediating capability, suggesting that vsx1A1 might play a more important role in regulating retina development.
These results indicate that (1) after genome duplication, the goldfish vsxl duplicates were retained by subfunctionalization;(2)the subfunctionalization of the goldfish vsxl duplicates were accomplished by complementary loss of both transcription and translation regulatory elements, which resulted in the different spatio-temporal expression patterns of vsxlAl and vsx1A2; (3) Both the complementary loss of transcription and translation regulatory elements and the intergenic synergetic divergences at transcription and translation regulatory regions of the duplicate vsxl genes are essential for the preserving of the vsxl duplicates and the partitioning of the developmental functions of ancestral vsxl.
引文
1. Stebbins G. L. Types of Polyploids-Their classification and significance. Advances in Genetics Incorporating Molecular Genetic Medicine 1947; 1:403-429.
2.-Masterson J. Stomatal Size in Fossil Plants-Evidence for polyploidy in majority of angiosperms. Science 1994;264:421-424.
3. Hughes M.K., Hughes A. L. Evolution of duplicate genes in a tetraploid animal, Xenopus-Laevis. Molecular Biology and Evolution 1993; 10:1360-1369.
4. Ohno S. Evolution by Gene Duplication. Heidelberg:Springer-Verlag, 1970
5. Holland P. W.H., Garciafernandez J., Williams N. A., Sidow A. Gene duplications and the origins of vertebrate development. Development 1994:125-133.
6.. Sidow A. Gen(om)e Duplications, in the Evolution of Early Vertebrates. Curr Opin Genet Dev 1996; 6:715-722.
7. Sharman A. C., Holland P. W. H. Conservation, duplication, and divergence of developmental genes during chordate evolution. Netherlands Journal of Zoology 1996; 46:47-67.
8. de Rosa R., Grenier J. K., Andreeva T., Cook C. E., Adoutte A., Akam M., Carroll S.B., Balavoine G. Hox genes in brachiopods and priapulids and protostome evolution. Nature 1999; 399:772-776.
9. Postlethwait J. H., Woods I.G., Ngo-Hazelett P., Yan Y. L., Kelly P.D., Chu F, Huang H, Hill-Force A., Talbot W. S. Zebrafish comparative genomics and the origins of vertebrate chromosomes. Genome Research 2000; 10:1890-1902.
10. Otto S. P., Whitton J. Polyploid incidence and evolution. Annual Review of Genetics 2000; 34:401-437.
11. Aburomia R., Khaner 0., Sidow A. Functional evolution in the ancestral lineage of vertebrates or when genomic complexity was wagging its morphological tail. J Struct Funct Genomics 2003; 3: 45-52.
12. Holland P. W. More genes in vertebrates? J Struct Funct Genomics 2003; 3:75-84.
13. Borel F., Lohez 0. D., Lacroix F. B., Margolis R. L. Multiple centrosomes arise from tetraploidy checkpoint failure and mitotic centrosome clusters in p53 and RB pocket protein-compromised cells. Proceedings of the National Academy of Sciences of the United States of America 2002; 99:9819-9824.
14. Song K. M., Lu P., Tang K. L., Osborn T. C. Rapid genome change in synthetic polyploids of brassica and its implications for polyploid evolution. Proceedings of the National Academy of Sciences of the United States of America 1995; 92:7719-7723.
15. Shaked H., Kashkush K., Ozkan H., Feldman M., Levy A. A. Sequence elimination and cytosine methylation are rapid and reproducible responses of the genome to wide hybridization and allopolyploidy in wheat. Plant Cell 2001; 13:1749-1759.
16. Comai L., Tyagi A. P., Winter K., Holmes-Davis R., Reynolds S. H., Stevens Y., Byers B. Phenotypic instability and rapid gene silencing in newly formed arabidopsis allotetraploids. Plant Cell 2000; 12:1551-1567.
17. Pikaard C. S. Genomic change and gene silencing in polyploids. Trends in Genetics 2001; 17:675-677.
18. Fisher R. A. The sheltering of lethals. American Naturalist 1935; 69:446-455.
19. Haldane J. B. S. The part played by recurrent mutation in evolution. American Naturalist 1933; 67:5-19.
20. Nadeau J. H., Sankoff D. Comparable rates of gene loss and functional divergence after genome duplications early in vertebrate evolution. Genetics 1997; 147:1259-1266.
21. Davis J. C., Petrov D. A. Do disparate mechanisms of duplication add similar genes to the genome? Trends in Genetics 2005; 21:548-551.
22. Meyer A., Van de Peer Y. From 2R to 3R:evidence for a fish-specific genome duplication (FSGD). Bioessays 2005; 27:937-945.
23. Freeling M., Thomas B.C. Gene-balanced duplications, like tetraploidy, provide predictable drive to increase morphological complexity. Genome Research 2006; 16:805-814.
24. Amoutzias G. D., He Y, Gordon J., Mossialos D., Oliver S. G., Van de Peer Y. Posttranslational regulation impacts the fate of duplicated genes. Proc Natl Acad Sci U S A 2010; 107:2967-2971.
25. Li W.H., Gu Z.L., Wang H.D., Nekrutenko A. Evolutionary analyses of the human genome. Nature 2001; 409:847-849.
26. Kaul S., Koo H. L., Jenkins J., Rizzo M., Rooney T., Tallon L. J., Feldblyum T., Nierman W., Benito M. I., Lin X.Y., Town C. D., Venter J. C., Fraser C.M., Tabata S., Nakamura Y., Kaneko T., Sato S., Asamizu E., Kato T., Kotani H., Sasamoto S., Ecker J. R., Theologis A., Federspiel N. A., Palm C. J., Osborne B. I., Shinn P., Conway A. B., Vysotskaia V. S., Dewar K., Conn L., Lenz C. A., Kim C. J., Hansen N. F., Liu S. X., Buehler E., Altaf i H., Sakano H., Dunn P., Lam B., Pham P. K., Chao Q., Nguyen M., Yu G. X., Chen H. M., Southwick A., Lee J. M., Miranda M., Toriumi M. J., Davis R. W., Wambutt R., Murphy G., Dusterhoft A., Stiekema W., Pohl T., Entian K. D., Terryn N., Volckaert G., Salanoubat M., Choisne N., Rieger M., Ansorge W., Unseld M., Fartmann B., Valle G., Artiguenave F., Weissenbach J., Quetier F., Wilson R. K., de la Bastide M., Sekhon M., Huang E., Spiegel L., Gnoj L., Pepin K., Murray J., Johnson D., Habermann K., Dedhia N., Parnell L., Preston R., Hillier L., Chen E., Marra M., Martienssen R, McCombie WR, Mayer K, White 0, Bevan M, Lemcke K, Creasy T.H., Bielke. C, Haas B., Haase D., Maiti R., Rudd S., Peterson J., Schoof H., Frishman D., Morgenstern B., et al. Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. ature 2000; 408:796-815.
27. Force A., Lynch M., Pickett F. B., Amores A., Yan Y. L., Postlethwait J. Preservation of duplicate genes by complementary, degenerative mutations. Genetics 1999; 151:1531-1545.
28. Lynch M., Conery J.S. The evolutionary fate and consequences of duplicate genes. Science 2000; 290:1151-1155.
29. Edelman G.M., Meech R., Owens G. C., Jones F. S. Synthetic promoter elements obtained by nucleotide sequence variation and selection for activity. Proceedings of the National Academy of Sciences of the United States of America 2000; 97:3038-3043.
30. Yuh C. H., Bolouri H., Davidson E. H. Cis-regulatory logic in the endo16 gene:switching from a specification to a differentiation mode of control. Development 2001; 128:617-629.
31. Carroll S. B. Endless forms:the evolution of gene regulation and morphological diversity. Cell 2000; 101:577-580.
32. Prince V. E., Pickett F. B. Splitting pairs:The diverging fates of duplicated genes. Nature Reviews Genetics 2002; 3:827-837.
33. Bruce A. E. E, Oates A. C., Prince V. E., Ho R. K. Additional hox clusters in the zebrafish:divergent expression patterns belie equivalent activities of duplicate hoxB5 genes. Evolution & Development 2001; 3:127-144.
34. Jarinova 0., Hatch G., Poitras L., Prudhomme C., Grzyb M., Aubin J., Berube-Simard F. A., Jeannotte L., Ekker M. Functional resolution of duplicated hoxb5 genes in teleosts. Development 2008; 135:3543-3553.
35. McClintock J. M., Kheirbek M. A., Prince V. E. Knockdown of duplicated zebrafish hoxbl genes reveals distinct roles in hindbrain patterning and a novel mechanism of duplicate gene retention. Development 2002; 129:2339-2354.
36. Studer M., Gavalas A., Marshall H., Ariza-McNaughton L., Rijli F. M., Chambon P., Krumlauf R. Genetic interactions between Hoxal and Hoxbl reveal new roles in regulation of early hindbrain patterning. Development 1998; 125:1025-1036.
37. Popperl H., Bienz M., Studer M., Chan S..-K., Aparicio S., Brenner S., Mann R. S., Krumlauf R. Segmental expression of hoxb-1 is controlled by a highly conserved autoregulatory loop dependent upon Exd/Pbx. Cell 1995; 81:1031-1042.
38. Studer M., Lumsden A., ArizaMcNaughton L., Bradley A., Krumlauf R. Altered segmental identity and abnormal migration of motor neurons in mice lacking Hoxb-1. Nature 1996; 384:630-634.
39. Goddard J. M., Rossel M., Manley N. R., Capecchi M. R. Mice with targeted disruption of Hoxb-1 fail to form the motor nucleus of the VIIth nerve. Development 1996; 122:3217-3228.
40. Gaufo 0.0., Flodby P, Capecchi M. R. Hoxbl controls effectors of sonic hedgehog and Mashl signaling pathways. Development 2000; 127: 5343-5354.
41. Bergsland M., Werme M., Malewicz M., Perlmann T., Muhr J. The establishment of neuronal properties is controlled by Sox4 and Soxll. Genes Dev 2006; 20:3475-3486.
42. Jankowski M. P., Cornuet P. K., McILwrath S., Koerber H. R., Albers K.M. SRY-box containing gene 11 (Soxll) transcription factor is required for neuron survival and neurite growth. Neuroscience 2006; 143:501-514.
43. Uwanogho D., Rex M., Cartwright E. J., Pearl G., Healy C., Scotting P. J., Sharpe P. T. Embryonic expression of the chicken sox2, sox3 and soxll genes suggests an interactive role in neuronal development. Mechanisms of Development 1995; 49:23-36.
44. Hargrave M., Wright E., Kun J., Emery J., Cooper L., Koopman P. Expression of the Soxll gene in mouse embryos suggests roles in neuronal maturation and epithelio-mesenchymal induction. Developmental Dynamics 1997; 210:79-86.
45. Sock E., Rettig S. D., Enderich J., Bosl M. R., Tamm E. R., Wegner M. Gene targeting reveals a widespread role for the high-mobility-group transcription factor Soxll in tissue remodeling. Molecular and Cellular Biology 2004; 24:6635-6644.
46. de Martino S., Yan Y. L., Jowett T., Postlethwait J. H., Varga Z. M., Ashworth A., Austin C. A. Expression of soxll gene duplicates in zebrafish suggests the reciprocal loss of ancestral gene expression patterns in development. Dev Dyn 2000; 217:279-292.
47. Navratilova P., Fredman D., Lenhard B., Becker T.S. Regulatory divergence of the duplicated chromosomal loci soxlla/b by ubpartitioning and sequence evolution of enhancsrs in zebrafish. Molecular Genetics and Genomics 2010; 283:171-184.
48. Tassabehji M., Newton V. E., Read A. P. Waardenburg Syndrome type-2 caused by mutations in the human mi crophthalmia (Mitf) gene. Nature Genetics 1994; 8:251-255.
49. Smith S. D, Kelley P.M., Kenyon J. B., Hoover D. Tietz syndrome (hypopigmentation/deafness) caused by mutation of MITF. Journal of Medical Genetics 2000; 37:446-448.
50. Hodgkinson C. A., Moore K. J., Nakayama A., Steingrimsson E., Copeland N. G., Jenkins N. A., Arnheiter H. Mutations at the mouse mi crophthalmia locus are associated with defects in a gene encoding a novel basic-helix-loop-helix-zipper protein. Cell 1993; 74: 395-404.
51. Lister J. A., Robertson C. P., Lepage T., Johnson S. L., Raible D. W. nacre encodes a zebrafish microphthalmia-related protein that regulates neural-crest-derived pigment cell fate. Development 1999; 126:3757-3767.
52. Lister J. A., Close J., Raible D.W. Subfunctionalization of duplicate mitf genes in zebrafish. Developmental Biology 2001; 235: 239-240.
53. Altschmied J., Delfgaauw J., Wilde B., Duschl J., Bouneau L., Volff J. N., Schartl M. Subfunctionalization of duplicate mitf genes associated with differential degeneration of alternative exons in fish. Genetics 2002; 161:259-267.
54. Yu W. P., Brenner S., Venkatesh B. Duplication, degeneration and subfunctionalization of the nested synapsin-Timp genes in Fugu. Trends in Genetics 2003; 19:180-183.
55. de Souza F. S., Bumaschny V. F., Low M. J., Rubinstein M. Subfunctionalization of expression and peptide domains following the ancient duplication of the proopiomelanocortin gene in teleost fishes. Mol Biol Evol 2005; 22:2417-2427.
56. Zhou L, Gui J.F. Karyotypic diversity in polyploid gibel carp, Carassius auratus gibelio Bloch. Genetica 2002; 115:223-232.
57. Yang L, Gui J. F. Positive selection on multiple antique allelic lineages of transferrin in the polyploid Carassius auratus. Mol Biol Evol 2004; 21:1264-1277.
58. Risinger C., Larhammar D. Multiple loci for synapse protein snap-25 in the tetraploid goldfish. Proceedings of the National Academy of Sciences of the United States of America 1993; 90:10598-10602.
59. Luo C, Li B. Diploid-dependent regulation of gene expression:a genetic cause of abnormal development in fish haploid embryos. Heredity 2003; 90:405-409.
60. 郑康.脊椎动物多倍体祖先二倍化的分子机制研究.湖南师范大学：博士学位论文2008.
61. Decembrini S., Andreazzoli M., Vignali R., Barsacchi G., Cremisi F. Timing the generation of distinct retinal cells by homeobox proteins. Plos Biology 2006; 4:1562-1571.
62. Decembrini S., Bressan D., Vignali R., Pitto L., Mariotti S. Rainaldi G., Wang X., Evangelista M., Barsacchi G., Cremisi F. MicroRNAs couple cell fate and developmental timing in retina. Proceedings of the National Academy of Sciences of the United States of America 2009; 106:21179-21184.
63. Chen J, Tong Y, Zhao S, Ma S, Luo C. vsxl 3' untranslated region-mediated translation difference at different developmental stages of goldfish embryos. J Genet Genomics 2009; 36:483-490.
64. Levine E. M., Schechter N. Homeobox genes are expressed in the retina and brain of adult goldfish. Proceedings of the National Academy of Sciences of the United States of America 1993; 90:2729-2733.
65. Levine E. M., Hitchcock P. F., Glasgow E., Schechter N. Restricted expression of a new paired-class homeobox gene in normal and regenerating adult goldfish retina. Journal of Comparative Neurology 1994; 348:596-606.
66. Passini M. A., Kurtzman A. L., Canger A. K., Asch W. S., Wray G. A. Raymond P. A., Schechter N. Cloning of zebrafish vsxl:expression of a paired-like homeobox gene during CNS development. Dev Genet 1998; 23:128-141.
67. Hayashi T., Huang J., Deeb S. S. RINX(VSXl), a novel homeobox gene expressed in the inner nuclear layer of the adult retina. Genomics 2000; 67:128-139.
68. Ohtoshi A., Justice M. J., Behringer R.R. Isolation and characterization of vsxl, a novel mouse CVC paired-like homeobox gene expressed during embryogenesis and in the retina. Biochemical and Biophysical Research Communications 2001; 286:133-140.
69. Chen C. M., Cepko C. L. Expression of Chx10 and Chx10-1 in the developing chicken retina. Mech Dev 2000; 90:293-297.
70. Semina E. V., Mintz-Hittner H. A., Murray J. C. Isolation and characterization of a novel human paired-like homeodomain-containing transcription factor gene, VSX1, expressed in ocular tissues. Genomics 2000; 63:289-293.
71. D'Autilia S., Decembrini S., Casarosa S., He R. Q., Barsacchi G., Cremisi F., Andreazzoli M. Cloning and developmental expression of the Xenopus homeobox gene Xvsxl. Dev Genes Evol 2006; 216:829-834.
72. Erclik T., Hartenstein V., Lipshitz H. D., Mclnnes R. R. Conserved role of the Vsx genes supports a monophyletic origin for bilaterian visual systems. Current Biology 2008; 18:1278-1287.
73. Tong Y, L B X, Chen J H, Luo C. Analysis on genomic structure and intron polymorphism of goldfish vsxl. acta kaser biology sinica 2007; 16:418-423.
74. Svendsen P. C., Mcghee J. D. The C-elegans neuronall-y expressed, homeobox gene ceh-10 is closely-related to genes expressed in the vertebrate eye. Development 1995; 121:1253-1262.
75. Dorval K.M., Bobechko B. P., Ahmad K. F., Bremner R. Transcriptional activity of the paired-like homeodomain proteins CHX10 and VSX1. Journal of Biological Chemistry 2005; 280:10100-10108.
76. Forrester W.C., Perens E., Zallen J.A., Garriga G. Identification of Caenorhabditis elegans genes required for neuronal differentiation and migration. Genetics 1998; 148:151-165.
77. Finkelstein R., Smouse D., Capaci T. M., Spradling A. C., Perrimon N. The orthodenticle gene encodes a novel homeodomain protein involved in the development of the drosophila nervous-system and ocellar visual structures. Genes & Development 1990; 4:1516-1527.
78. Schneitz K., Spielmann P., Noll M. Molecular-genetics of aristaless, a prd-type homeobox gene involved in the morphogenesis of proximal and distal pattern elements in a subset of appendages in Drosophila. Genes & Development 1993; 7:114-129.
79. Hanes S. D., Brent R. A genetic model for interaction of the homeodomain recognition helix with DNA. Science 1991; 251:426-430.
80. Zhang QY, Zheng K, Ma S. S, Tong Y, Luo C. Goldfish beta-catenin cell-autonomously inhibits the expression of early neural development regulating gene vsxl. Chinese Science Bulletin 2010; 55:145-152.
81. Passini M. A., Levine E. M., Canger A. K., Raymond P. A., Schechter N. Vsx-1 and Vsx-2:Differential expression of two paired-like homeobox genes during zebrafish and goldfish retinogenesis. Journal of Comparative Neurology 1997; 388:495-505.
82. Levine E. M., Passini M., Hitchcock P..F., Glasgow E., Schechter N. Vsx-1 and Vsx-2:Two ChxlO-like homeobox genes expressed in overlapping domains in the adult goldfish retina. Journal of Comparative Neurology 1997; 387:439-448.
83. Huang L, Li B, Luo C, Xie J, Chen P, Liang S. Proteome comparative analysis of gynogenetic haploid and diploid embryos of goldfish (Carassius auratus). Proteomics 2004; 4:235-243.
84. Chow R. L., Snow B., Novak J., Looser J., Freund C., Vidgen D., Ploder L., Mclnnes R. R. Vsxl, a rapidly evolving paired-like homeobox gene expressed in cone bipolar cells. Mech Dev 2001; 109:315-322.
85. Ohtoshi A., Wang S. W., Maeda H., Saszik S.M., Frishman L. J., Klein W. H., Behringer R. R. Regulation of retinal cone bipolar cell differentiation and photopic vision by the CVC homeobox gene Vsxl. Current Biology 2004; 14:530-536.
86. Heon E., Greenberg A., Kopp K. K., Rootman D., Vincent A. L., Billingsley G., Priston M., Dorval K. M., Chow R. L., Mclnnes R. R., Heathcote G., Westall C., Sutphin J. E., Semina E., Bremner R., Stone E. M. VSX1:A gene for posterior polymorphous dystrophy and keratoconus. Human Molecular Genetics 2002; 11:1029-1036.
87. Valleix S., Nedelec B., Rigaudiere F., Dighiero P., Pouliquen Y. Renard G., Le Gargasson J. F., Delpech M. H244R VSX1 is associated with selective cone ON bipolar cell dysfunction and macular degeneration in a PPCD family. Investigative Ophthalmology & Visual Science 2006; 47:48-54.
88. Stabuc-Silih M., Stra-zisar M., Ravnik-Glavac M., Hawlina M., Glavac D. Genetics and clinical characteristics of keratoconus. Acta Dermatovenerol Alp Panonica Adriat; 19:3-10.
89. Paliwal P., Singh A., Tandon R., Titiyal J. S., Sharma A. A novel VSX1 mutation identified in an individual with keratoconus in India. Mol Vis 2009; 15:2475-2479.
90. Liu Z H, Chen J H, Ma S. S, Tong Y, Luo C. Goldfish vsxl inhibits chordamesoderm gene ntl expression at the,dorsal midline. Chinese Science Bulletin 2009; 54:1345-1353.
91. Clark A. M., Yun S., Veien E. S., Wu Y. Y., Chow R. L.,. Dorsky R. I. Levine EM. Negative regulation of Vsxl by its paralog Chx10/Vsx2 is conserved in the vertebrate retina. Brain Res 2008; 1192:99-113.
92. Harland R. M. In-situ hybridization-an improved whole-mount method for Xenopus-embryos. Methods in Cell Biology 1991; 36:685-695.
93. Vanholme B., De Meutter J., Tytgat T., Gheysen G. D.C., Vanhoutte I., Gheysen G. D. R. An improved method for whole-mount in situ hybridization of Heterodera schachtii juveniles. Parasitology Research 2002; 88:731-733.
94. Meng A. M., Tang H., Ong B. A., Farrell M. J., Lin S. Promoter analysis in living zebrafish embryos identifies a cis-acting motif required for neuronal expression of GATA-2. Proceedings of the National Academy of Sciences of the United States of America 1997; 94: 6267-6272.
95. Fisher S., Grice E. A., Vinton R. M., Bessling S. L., Urasaki A., Kawakami K., McCallion A. S. Evaluating the biological relevance of putative enhancers using To12 transposon-mediated transgenesis in zebrafish. Nature Protocols 2006; 1:1297-1305.
96. Riminton D.S.. Gene targeting technology and advances in the pathophysiology of inflammation. Pathology 2002; 34:109-114.
97. Thompson J. D., Gibson T. J., Plewniak F., Jeanmougin F., Higgins D. G. The CLUSTAL_X windows interface:flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 1997; 25:4876-4882.
98. Tamura K., Dudley J., Nei M., Kumar S. MEGA4:Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol 2007; 24:1596-1599.
99. Grimson A, Farh KKH, Johnston WK, Garrett-Engele P, Lim LP, Bartel DP. MicroRNA targeting specificity in mammals:Determinants beyond seed pairing. Molecular Cell 2007; 27:91-105.
100. Krek A., Grun D., Poy M. N., Wolf R., Rosenberg L., Epstein E. J., MacMenamin P., da Piedade I., Gunsalus K. C., Stoffel M., Rajewsky N. Combinatorial microRNA target predictions. Nature Genetics 2005; 37:495-500.
101. Enright A. J, John B., Gaul U., Tuschl T., Sander C., Marks D. S. MicroRNA targets in Drosophila. Genome Biology 2004; 5(1):R1.
102. Griffiths-Jones S., Saini H. K., van Dongen S., Enright A. J. miRBase: tools for microRNA genomics. Nucleic Acids Research 2008; 36: D154-D158..
103. Reinhart B. J., Slack F. J., Basson M., Pasquinelli A. E., Bettinger J. C., Rougvie A. E., Horvitz H. R., Ruvkun G. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 2000; 403:901-906.
104. Pasquinelli A. E., Reinhart B. J., Slack F., Martindale M. Q.:, Kuroda M. I., Maller B., Hayward D. C., Ball E. E., Degnan B., Muller P., Spring J., Srinivasan A., Fishman M., Finnerty J., Corbo J., Levine M., Leahy P., Davidson E., Ruvkun G. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 2000;,408:86-89.
105. Sokol N. S., Xu P. Z., Jan Y. N., Ambros V. Drosophila let-7 microRNA is. required for remodeling of the neuromusculature during metamorphosis. Genes & Development 2008; 22:1591-1596.
106. Christoffels A., Koh E. G. L., Chia J.M., Brenner S., Aparicio S., Venkatesh B. Fugu genome analysis provides evidence for a whole-genome duplication early during the evolution of ray-finned fishes. Molecular Biology and Evolution 2004; 21:1146-1151.
107. Jaillon 0., Aury J. M., Brunet F., Petit J. L., Stange-Thomann N., Mauceli E., Bouneau L., Fischer C., Ozouf-Costaz C., Bernot A., Nicaud S., Jaffe D., Fisher S., Lutfalla G., Dossat C., Segurens B., Dasilva C., Salanoubat M., Levy M., Boudet N., Castellano S., Anthouard V., Jubin C., Castelli V., Katinka M., Vacherie B., Biemont C., Skalli Z., Cattolico L., Poulain J., De Berardinis V., Cruaud C., Duprat S., Brottier P., Coutanceau J. P., Gouzy J., Parra G., Lardier G., Chapple C., McKernan K. J., McEwan P., Bosak S., Kellis M., Volff J.N., Guigo R., Zody M.C., Mesirov J., Lindblad-Toh K., Birren B., Nusbaum C., Kahn D., Robinson-Rechavi M., Laudet V., Schachter V., Quetier F., Saurin W., Scarpelli C., Wincker P. Lander E. S., Weissenbach J., Roest Crollius H. Genome duplication in the teleost fish Tetraodon nigroviridis reveals the early vertebrate proto-karyotype. Nature 2004; 431:946-957.
108. Liu R. Z., Sun Q., Thisse C., Thisse B., Wright J. M., Denovan-Wright E. M.. The cellular retinol-binding protein genes are duplicated and differentially transcribed in the developing and adult zebrafish (Danio rerio) (vol 22, pg 469,2005). Molecular Biology and Evolution 2005; 22:1157-1157.
109. Kleinjan D.A., Bancewicz R. M., Gautier P., Dahm R., Schonthaler H..B.,. Damante G., Seawright A., Hever A.M., Yeyati P. L., van Heyningen V., Coutinho P. Subfunctionalization of duplicated zebrafish pax6 genes by cis-regulatory divergence. PLoS Genet 2008; 4:e29.
110. Volff J.N. Genome evolution and biodiversity in teleost fish. Heredity 2005; 94:280-294.
111. Semon M., Wolfe K. H. Consequences of genome duplication. Curr Opin Genet Dev 2007; 17:505-512.
112. Kuersten S., Goodwin E. B. The power of the 3'UTR:Translational control and development. Nature Reviews Genetics 2003; 4:626-637.
113. Dean K. A., Aggarwal A. K., Wharton R. P. Translational repressors in Drosophila. Trends in Genetics 2002; 18:572-577.
114. Sonoda J., Wharton R. P. Recruitment of Nanos to hunchback mRNA by Pumilio. Genes & Development 1999; 13:2704-2712.
115. Sonoda J., Wharton R. P. Drosophila brain tumor is a translational repressor. Genes & Development 2001; 15:762-773.
116. Wharton R. P., Struhl G. RNA regulatory elements mediate control of drosophila body pattern by the posterior morphogen nanos. Cell 1991; 67:955-967.
117. Murata Y., Wharton R. P. Binding of pumilio to maternal hunchback messenger-RNA Is required for posterior patterning in drosophila embryos. Cell 1995; 80:747-756.
118. Bergsten S.E., Gavis E. R. Role for mRNA localization in translational activation but not spatial restriction of nanos RNA. Development 1999; 126:659-669.
119. Ephrussi A., Dickinson L. K., Lehmann R. Oskar organizes the germ plasm and directs localization of the posterior determinant nanos. Cell 1991; 66:37-50.
120. Gavis E. R., Lehmann R. Localization of nanos RNA controls embryonic polarity. Cell 1992; 71:301-313.
121. Smith J. L., Wilson J. E., Macdonald P.M. Overexpression of oskar directs ectopic activation of nanos and presumptive pole cell-formation in drosophila embryos. Cell 1992; 70:849-859.
122. Dahanukar A., Walker J. A., Wharton R. P. Smaug, a novel RNA-binding protein that operates a translational switch in Drosophila. Molecular Cell 1999; 4:209-218.
123. Smibert C. A., Lie Y. S., Shillinglaw W., Henzel W. J., Macdonald P. M. Smaug, a novel and conserved protein, contributes to repression of nanos mRNA translation in vitro. Rna-a Publication of the Rna Society 1999; 5:_1535-1547.
124. Smibert C. A., Wilson J. E., Kerr K., Macdonald P.M. smaug protein represses translation of unlocalized nanos mRNA in the Drosophila embryo. Genes & Development 1996; 10:2600-2609.
125. Rougvie A. E. Control of developmental timing in animals. Nature Reviews Genetics 2001; 2:690-701.
126. Slack F. J., Basson M., Liu Z. C., Ambros V., Horvitz H. R., Ruvkun G. The lin-41 RBCC gene acts in the C-elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor. Molecular Cell 2000; 5:659-669.
127. Newman A. P., Inoue T., Wang M. Q., Sternberg P. W. The Caenorhabditis elegans heterochronic gene lin-29 coordinates the vulval-uterine-epidermal connections. Current Biology 2000; 10: 1479-1488.
2.-Masterson J. Stomatal Size in Fossil Plants-Evidence for polyploidy in majority of angiosperms. Science 1994;264:421-424.
3. Hughes M.K., Hughes A. L. Evolution of duplicate genes in a tetraploid animal, Xenopus-Laevis. Molecular Biology and Evolution 1993; 10:1360-1369.
4. Ohno S. Evolution by Gene Duplication. Heidelberg:Springer-Verlag, 1970
5. Holland P. W.H., Garciafernandez J., Williams N. A., Sidow A. Gene duplications and the origins of vertebrate development. Development 1994:125-133.
6.. Sidow A. Gen(om)e Duplications, in the Evolution of Early Vertebrates. Curr Opin Genet Dev 1996; 6:715-722.
7. Sharman A. C., Holland P. W. H. Conservation, duplication, and divergence of developmental genes during chordate evolution. Netherlands Journal of Zoology 1996; 46:47-67.
8. de Rosa R., Grenier J. K., Andreeva T., Cook C. E., Adoutte A., Akam M., Carroll S.B., Balavoine G. Hox genes in brachiopods and priapulids and protostome evolution. Nature 1999; 399:772-776.
9. Postlethwait J. H., Woods I.G., Ngo-Hazelett P., Yan Y. L., Kelly P.D., Chu F, Huang H, Hill-Force A., Talbot W. S. Zebrafish comparative genomics and the origins of vertebrate chromosomes. Genome Research 2000; 10:1890-1902.
10. Otto S. P., Whitton J. Polyploid incidence and evolution. Annual Review of Genetics 2000; 34:401-437.
11. Aburomia R., Khaner 0., Sidow A. Functional evolution in the ancestral lineage of vertebrates or when genomic complexity was wagging its morphological tail. J Struct Funct Genomics 2003; 3: 45-52.
12. Holland P. W. More genes in vertebrates? J Struct Funct Genomics 2003; 3:75-84.
13. Borel F., Lohez 0. D., Lacroix F. B., Margolis R. L. Multiple centrosomes arise from tetraploidy checkpoint failure and mitotic centrosome clusters in p53 and RB pocket protein-compromised cells. Proceedings of the National Academy of Sciences of the United States of America 2002; 99:9819-9824.
14. Song K. M., Lu P., Tang K. L., Osborn T. C. Rapid genome change in synthetic polyploids of brassica and its implications for polyploid evolution. Proceedings of the National Academy of Sciences of the United States of America 1995; 92:7719-7723.
15. Shaked H., Kashkush K., Ozkan H., Feldman M., Levy A. A. Sequence elimination and cytosine methylation are rapid and reproducible responses of the genome to wide hybridization and allopolyploidy in wheat. Plant Cell 2001; 13:1749-1759.
16. Comai L., Tyagi A. P., Winter K., Holmes-Davis R., Reynolds S. H., Stevens Y., Byers B. Phenotypic instability and rapid gene silencing in newly formed arabidopsis allotetraploids. Plant Cell 2000; 12:1551-1567.
17. Pikaard C. S. Genomic change and gene silencing in polyploids. Trends in Genetics 2001; 17:675-677.
18. Fisher R. A. The sheltering of lethals. American Naturalist 1935; 69:446-455.
19. Haldane J. B. S. The part played by recurrent mutation in evolution. American Naturalist 1933; 67:5-19.
20. Nadeau J. H., Sankoff D. Comparable rates of gene loss and functional divergence after genome duplications early in vertebrate evolution. Genetics 1997; 147:1259-1266.
21. Davis J. C., Petrov D. A. Do disparate mechanisms of duplication add similar genes to the genome? Trends in Genetics 2005; 21:548-551.
22. Meyer A., Van de Peer Y. From 2R to 3R:evidence for a fish-specific genome duplication (FSGD). Bioessays 2005; 27:937-945.
23. Freeling M., Thomas B.C. Gene-balanced duplications, like tetraploidy, provide predictable drive to increase morphological complexity. Genome Research 2006; 16:805-814.
24. Amoutzias G. D., He Y, Gordon J., Mossialos D., Oliver S. G., Van de Peer Y. Posttranslational regulation impacts the fate of duplicated genes. Proc Natl Acad Sci U S A 2010; 107:2967-2971.
25. Li W.H., Gu Z.L., Wang H.D., Nekrutenko A. Evolutionary analyses of the human genome. Nature 2001; 409:847-849.
26. Kaul S., Koo H. L., Jenkins J., Rizzo M., Rooney T., Tallon L. J., Feldblyum T., Nierman W., Benito M. I., Lin X.Y., Town C. D., Venter J. C., Fraser C.M., Tabata S., Nakamura Y., Kaneko T., Sato S., Asamizu E., Kato T., Kotani H., Sasamoto S., Ecker J. R., Theologis A., Federspiel N. A., Palm C. J., Osborne B. I., Shinn P., Conway A. B., Vysotskaia V. S., Dewar K., Conn L., Lenz C. A., Kim C. J., Hansen N. F., Liu S. X., Buehler E., Altaf i H., Sakano H., Dunn P., Lam B., Pham P. K., Chao Q., Nguyen M., Yu G. X., Chen H. M., Southwick A., Lee J. M., Miranda M., Toriumi M. J., Davis R. W., Wambutt R., Murphy G., Dusterhoft A., Stiekema W., Pohl T., Entian K. D., Terryn N., Volckaert G., Salanoubat M., Choisne N., Rieger M., Ansorge W., Unseld M., Fartmann B., Valle G., Artiguenave F., Weissenbach J., Quetier F., Wilson R. K., de la Bastide M., Sekhon M., Huang E., Spiegel L., Gnoj L., Pepin K., Murray J., Johnson D., Habermann K., Dedhia N., Parnell L., Preston R., Hillier L., Chen E., Marra M., Martienssen R, McCombie WR, Mayer K, White 0, Bevan M, Lemcke K, Creasy T.H., Bielke. C, Haas B., Haase D., Maiti R., Rudd S., Peterson J., Schoof H., Frishman D., Morgenstern B., et al. Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. ature 2000; 408:796-815.
27. Force A., Lynch M., Pickett F. B., Amores A., Yan Y. L., Postlethwait J. Preservation of duplicate genes by complementary, degenerative mutations. Genetics 1999; 151:1531-1545.
28. Lynch M., Conery J.S. The evolutionary fate and consequences of duplicate genes. Science 2000; 290:1151-1155.
29. Edelman G.M., Meech R., Owens G. C., Jones F. S. Synthetic promoter elements obtained by nucleotide sequence variation and selection for activity. Proceedings of the National Academy of Sciences of the United States of America 2000; 97:3038-3043.
30. Yuh C. H., Bolouri H., Davidson E. H. Cis-regulatory logic in the endo16 gene:switching from a specification to a differentiation mode of control. Development 2001; 128:617-629.
31. Carroll S. B. Endless forms:the evolution of gene regulation and morphological diversity. Cell 2000; 101:577-580.
32. Prince V. E., Pickett F. B. Splitting pairs:The diverging fates of duplicated genes. Nature Reviews Genetics 2002; 3:827-837.
33. Bruce A. E. E, Oates A. C., Prince V. E., Ho R. K. Additional hox clusters in the zebrafish:divergent expression patterns belie equivalent activities of duplicate hoxB5 genes. Evolution & Development 2001; 3:127-144.
34. Jarinova 0., Hatch G., Poitras L., Prudhomme C., Grzyb M., Aubin J., Berube-Simard F. A., Jeannotte L., Ekker M. Functional resolution of duplicated hoxb5 genes in teleosts. Development 2008; 135:3543-3553.
35. McClintock J. M., Kheirbek M. A., Prince V. E. Knockdown of duplicated zebrafish hoxbl genes reveals distinct roles in hindbrain patterning and a novel mechanism of duplicate gene retention. Development 2002; 129:2339-2354.
36. Studer M., Gavalas A., Marshall H., Ariza-McNaughton L., Rijli F. M., Chambon P., Krumlauf R. Genetic interactions between Hoxal and Hoxbl reveal new roles in regulation of early hindbrain patterning. Development 1998; 125:1025-1036.
37. Popperl H., Bienz M., Studer M., Chan S..-K., Aparicio S., Brenner S., Mann R. S., Krumlauf R. Segmental expression of hoxb-1 is controlled by a highly conserved autoregulatory loop dependent upon Exd/Pbx. Cell 1995; 81:1031-1042.
38. Studer M., Lumsden A., ArizaMcNaughton L., Bradley A., Krumlauf R. Altered segmental identity and abnormal migration of motor neurons in mice lacking Hoxb-1. Nature 1996; 384:630-634.
39. Goddard J. M., Rossel M., Manley N. R., Capecchi M. R. Mice with targeted disruption of Hoxb-1 fail to form the motor nucleus of the VIIth nerve. Development 1996; 122:3217-3228.
40. Gaufo 0.0., Flodby P, Capecchi M. R. Hoxbl controls effectors of sonic hedgehog and Mashl signaling pathways. Development 2000; 127: 5343-5354.
41. Bergsland M., Werme M., Malewicz M., Perlmann T., Muhr J. The establishment of neuronal properties is controlled by Sox4 and Soxll. Genes Dev 2006; 20:3475-3486.
42. Jankowski M. P., Cornuet P. K., McILwrath S., Koerber H. R., Albers K.M. SRY-box containing gene 11 (Soxll) transcription factor is required for neuron survival and neurite growth. Neuroscience 2006; 143:501-514.
43. Uwanogho D., Rex M., Cartwright E. J., Pearl G., Healy C., Scotting P. J., Sharpe P. T. Embryonic expression of the chicken sox2, sox3 and soxll genes suggests an interactive role in neuronal development. Mechanisms of Development 1995; 49:23-36.
44. Hargrave M., Wright E., Kun J., Emery J., Cooper L., Koopman P. Expression of the Soxll gene in mouse embryos suggests roles in neuronal maturation and epithelio-mesenchymal induction. Developmental Dynamics 1997; 210:79-86.
45. Sock E., Rettig S. D., Enderich J., Bosl M. R., Tamm E. R., Wegner M. Gene targeting reveals a widespread role for the high-mobility-group transcription factor Soxll in tissue remodeling. Molecular and Cellular Biology 2004; 24:6635-6644.
46. de Martino S., Yan Y. L., Jowett T., Postlethwait J. H., Varga Z. M., Ashworth A., Austin C. A. Expression of soxll gene duplicates in zebrafish suggests the reciprocal loss of ancestral gene expression patterns in development. Dev Dyn 2000; 217:279-292.
47. Navratilova P., Fredman D., Lenhard B., Becker T.S. Regulatory divergence of the duplicated chromosomal loci soxlla/b by ubpartitioning and sequence evolution of enhancsrs in zebrafish. Molecular Genetics and Genomics 2010; 283:171-184.
48. Tassabehji M., Newton V. E., Read A. P. Waardenburg Syndrome type-2 caused by mutations in the human mi crophthalmia (Mitf) gene. Nature Genetics 1994; 8:251-255.
49. Smith S. D, Kelley P.M., Kenyon J. B., Hoover D. Tietz syndrome (hypopigmentation/deafness) caused by mutation of MITF. Journal of Medical Genetics 2000; 37:446-448.
50. Hodgkinson C. A., Moore K. J., Nakayama A., Steingrimsson E., Copeland N. G., Jenkins N. A., Arnheiter H. Mutations at the mouse mi crophthalmia locus are associated with defects in a gene encoding a novel basic-helix-loop-helix-zipper protein. Cell 1993; 74: 395-404.
51. Lister J. A., Robertson C. P., Lepage T., Johnson S. L., Raible D. W. nacre encodes a zebrafish microphthalmia-related protein that regulates neural-crest-derived pigment cell fate. Development 1999; 126:3757-3767.
52. Lister J. A., Close J., Raible D.W. Subfunctionalization of duplicate mitf genes in zebrafish. Developmental Biology 2001; 235: 239-240.
53. Altschmied J., Delfgaauw J., Wilde B., Duschl J., Bouneau L., Volff J. N., Schartl M. Subfunctionalization of duplicate mitf genes associated with differential degeneration of alternative exons in fish. Genetics 2002; 161:259-267.
54. Yu W. P., Brenner S., Venkatesh B. Duplication, degeneration and subfunctionalization of the nested synapsin-Timp genes in Fugu. Trends in Genetics 2003; 19:180-183.
55. de Souza F. S., Bumaschny V. F., Low M. J., Rubinstein M. Subfunctionalization of expression and peptide domains following the ancient duplication of the proopiomelanocortin gene in teleost fishes. Mol Biol Evol 2005; 22:2417-2427.
56. Zhou L, Gui J.F. Karyotypic diversity in polyploid gibel carp, Carassius auratus gibelio Bloch. Genetica 2002; 115:223-232.
57. Yang L, Gui J. F. Positive selection on multiple antique allelic lineages of transferrin in the polyploid Carassius auratus. Mol Biol Evol 2004; 21:1264-1277.
58. Risinger C., Larhammar D. Multiple loci for synapse protein snap-25 in the tetraploid goldfish. Proceedings of the National Academy of Sciences of the United States of America 1993; 90:10598-10602.
59. Luo C, Li B. Diploid-dependent regulation of gene expression:a genetic cause of abnormal development in fish haploid embryos. Heredity 2003; 90:405-409.
60. 郑康.脊椎动物多倍体祖先二倍化的分子机制研究.湖南师范大学：博士学位论文2008.
61. Decembrini S., Andreazzoli M., Vignali R., Barsacchi G., Cremisi F. Timing the generation of distinct retinal cells by homeobox proteins. Plos Biology 2006; 4:1562-1571.
62. Decembrini S., Bressan D., Vignali R., Pitto L., Mariotti S. Rainaldi G., Wang X., Evangelista M., Barsacchi G., Cremisi F. MicroRNAs couple cell fate and developmental timing in retina. Proceedings of the National Academy of Sciences of the United States of America 2009; 106:21179-21184.
63. Chen J, Tong Y, Zhao S, Ma S, Luo C. vsxl 3' untranslated region-mediated translation difference at different developmental stages of goldfish embryos. J Genet Genomics 2009; 36:483-490.
64. Levine E. M., Schechter N. Homeobox genes are expressed in the retina and brain of adult goldfish. Proceedings of the National Academy of Sciences of the United States of America 1993; 90:2729-2733.
65. Levine E. M., Hitchcock P. F., Glasgow E., Schechter N. Restricted expression of a new paired-class homeobox gene in normal and regenerating adult goldfish retina. Journal of Comparative Neurology 1994; 348:596-606.
66. Passini M. A., Kurtzman A. L., Canger A. K., Asch W. S., Wray G. A. Raymond P. A., Schechter N. Cloning of zebrafish vsxl:expression of a paired-like homeobox gene during CNS development. Dev Genet 1998; 23:128-141.
67. Hayashi T., Huang J., Deeb S. S. RINX(VSXl), a novel homeobox gene expressed in the inner nuclear layer of the adult retina. Genomics 2000; 67:128-139.
68. Ohtoshi A., Justice M. J., Behringer R.R. Isolation and characterization of vsxl, a novel mouse CVC paired-like homeobox gene expressed during embryogenesis and in the retina. Biochemical and Biophysical Research Communications 2001; 286:133-140.
69. Chen C. M., Cepko C. L. Expression of Chx10 and Chx10-1 in the developing chicken retina. Mech Dev 2000; 90:293-297.
70. Semina E. V., Mintz-Hittner H. A., Murray J. C. Isolation and characterization of a novel human paired-like homeodomain-containing transcription factor gene, VSX1, expressed in ocular tissues. Genomics 2000; 63:289-293.
71. D'Autilia S., Decembrini S., Casarosa S., He R. Q., Barsacchi G., Cremisi F., Andreazzoli M. Cloning and developmental expression of the Xenopus homeobox gene Xvsxl. Dev Genes Evol 2006; 216:829-834.
72. Erclik T., Hartenstein V., Lipshitz H. D., Mclnnes R. R. Conserved role of the Vsx genes supports a monophyletic origin for bilaterian visual systems. Current Biology 2008; 18:1278-1287.
73. Tong Y, L B X, Chen J H, Luo C. Analysis on genomic structure and intron polymorphism of goldfish vsxl. acta kaser biology sinica 2007; 16:418-423.
74. Svendsen P. C., Mcghee J. D. The C-elegans neuronall-y expressed, homeobox gene ceh-10 is closely-related to genes expressed in the vertebrate eye. Development 1995; 121:1253-1262.
75. Dorval K.M., Bobechko B. P., Ahmad K. F., Bremner R. Transcriptional activity of the paired-like homeodomain proteins CHX10 and VSX1. Journal of Biological Chemistry 2005; 280:10100-10108.
76. Forrester W.C., Perens E., Zallen J.A., Garriga G. Identification of Caenorhabditis elegans genes required for neuronal differentiation and migration. Genetics 1998; 148:151-165.
77. Finkelstein R., Smouse D., Capaci T. M., Spradling A. C., Perrimon N. The orthodenticle gene encodes a novel homeodomain protein involved in the development of the drosophila nervous-system and ocellar visual structures. Genes & Development 1990; 4:1516-1527.
78. Schneitz K., Spielmann P., Noll M. Molecular-genetics of aristaless, a prd-type homeobox gene involved in the morphogenesis of proximal and distal pattern elements in a subset of appendages in Drosophila. Genes & Development 1993; 7:114-129.
79. Hanes S. D., Brent R. A genetic model for interaction of the homeodomain recognition helix with DNA. Science 1991; 251:426-430.
80. Zhang QY, Zheng K, Ma S. S, Tong Y, Luo C. Goldfish beta-catenin cell-autonomously inhibits the expression of early neural development regulating gene vsxl. Chinese Science Bulletin 2010; 55:145-152.
81. Passini M. A., Levine E. M., Canger A. K., Raymond P. A., Schechter N. Vsx-1 and Vsx-2:Differential expression of two paired-like homeobox genes during zebrafish and goldfish retinogenesis. Journal of Comparative Neurology 1997; 388:495-505.
82. Levine E. M., Passini M., Hitchcock P..F., Glasgow E., Schechter N. Vsx-1 and Vsx-2:Two ChxlO-like homeobox genes expressed in overlapping domains in the adult goldfish retina. Journal of Comparative Neurology 1997; 387:439-448.
83. Huang L, Li B, Luo C, Xie J, Chen P, Liang S. Proteome comparative analysis of gynogenetic haploid and diploid embryos of goldfish (Carassius auratus). Proteomics 2004; 4:235-243.
84. Chow R. L., Snow B., Novak J., Looser J., Freund C., Vidgen D., Ploder L., Mclnnes R. R. Vsxl, a rapidly evolving paired-like homeobox gene expressed in cone bipolar cells. Mech Dev 2001; 109:315-322.
85. Ohtoshi A., Wang S. W., Maeda H., Saszik S.M., Frishman L. J., Klein W. H., Behringer R. R. Regulation of retinal cone bipolar cell differentiation and photopic vision by the CVC homeobox gene Vsxl. Current Biology 2004; 14:530-536.
86. Heon E., Greenberg A., Kopp K. K., Rootman D., Vincent A. L., Billingsley G., Priston M., Dorval K. M., Chow R. L., Mclnnes R. R., Heathcote G., Westall C., Sutphin J. E., Semina E., Bremner R., Stone E. M. VSX1:A gene for posterior polymorphous dystrophy and keratoconus. Human Molecular Genetics 2002; 11:1029-1036.
87. Valleix S., Nedelec B., Rigaudiere F., Dighiero P., Pouliquen Y. Renard G., Le Gargasson J. F., Delpech M. H244R VSX1 is associated with selective cone ON bipolar cell dysfunction and macular degeneration in a PPCD family. Investigative Ophthalmology & Visual Science 2006; 47:48-54.
88. Stabuc-Silih M., Stra-zisar M., Ravnik-Glavac M., Hawlina M., Glavac D. Genetics and clinical characteristics of keratoconus. Acta Dermatovenerol Alp Panonica Adriat; 19:3-10.
89. Paliwal P., Singh A., Tandon R., Titiyal J. S., Sharma A. A novel VSX1 mutation identified in an individual with keratoconus in India. Mol Vis 2009; 15:2475-2479.
90. Liu Z H, Chen J H, Ma S. S, Tong Y, Luo C. Goldfish vsxl inhibits chordamesoderm gene ntl expression at the,dorsal midline. Chinese Science Bulletin 2009; 54:1345-1353.
91. Clark A. M., Yun S., Veien E. S., Wu Y. Y., Chow R. L.,. Dorsky R. I. Levine EM. Negative regulation of Vsxl by its paralog Chx10/Vsx2 is conserved in the vertebrate retina. Brain Res 2008; 1192:99-113.
92. Harland R. M. In-situ hybridization-an improved whole-mount method for Xenopus-embryos. Methods in Cell Biology 1991; 36:685-695.
93. Vanholme B., De Meutter J., Tytgat T., Gheysen G. D.C., Vanhoutte I., Gheysen G. D. R. An improved method for whole-mount in situ hybridization of Heterodera schachtii juveniles. Parasitology Research 2002; 88:731-733.
94. Meng A. M., Tang H., Ong B. A., Farrell M. J., Lin S. Promoter analysis in living zebrafish embryos identifies a cis-acting motif required for neuronal expression of GATA-2. Proceedings of the National Academy of Sciences of the United States of America 1997; 94: 6267-6272.
95. Fisher S., Grice E. A., Vinton R. M., Bessling S. L., Urasaki A., Kawakami K., McCallion A. S. Evaluating the biological relevance of putative enhancers using To12 transposon-mediated transgenesis in zebrafish. Nature Protocols 2006; 1:1297-1305.
96. Riminton D.S.. Gene targeting technology and advances in the pathophysiology of inflammation. Pathology 2002; 34:109-114.
97. Thompson J. D., Gibson T. J., Plewniak F., Jeanmougin F., Higgins D. G. The CLUSTAL_X windows interface:flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 1997; 25:4876-4882.
98. Tamura K., Dudley J., Nei M., Kumar S. MEGA4:Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol 2007; 24:1596-1599.
99. Grimson A, Farh KKH, Johnston WK, Garrett-Engele P, Lim LP, Bartel DP. MicroRNA targeting specificity in mammals:Determinants beyond seed pairing. Molecular Cell 2007; 27:91-105.
100. Krek A., Grun D., Poy M. N., Wolf R., Rosenberg L., Epstein E. J., MacMenamin P., da Piedade I., Gunsalus K. C., Stoffel M., Rajewsky N. Combinatorial microRNA target predictions. Nature Genetics 2005; 37:495-500.
101. Enright A. J, John B., Gaul U., Tuschl T., Sander C., Marks D. S. MicroRNA targets in Drosophila. Genome Biology 2004; 5(1):R1.
102. Griffiths-Jones S., Saini H. K., van Dongen S., Enright A. J. miRBase: tools for microRNA genomics. Nucleic Acids Research 2008; 36: D154-D158..
103. Reinhart B. J., Slack F. J., Basson M., Pasquinelli A. E., Bettinger J. C., Rougvie A. E., Horvitz H. R., Ruvkun G. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 2000; 403:901-906.
104. Pasquinelli A. E., Reinhart B. J., Slack F., Martindale M. Q.:, Kuroda M. I., Maller B., Hayward D. C., Ball E. E., Degnan B., Muller P., Spring J., Srinivasan A., Fishman M., Finnerty J., Corbo J., Levine M., Leahy P., Davidson E., Ruvkun G. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 2000;,408:86-89.
105. Sokol N. S., Xu P. Z., Jan Y. N., Ambros V. Drosophila let-7 microRNA is. required for remodeling of the neuromusculature during metamorphosis. Genes & Development 2008; 22:1591-1596.
106. Christoffels A., Koh E. G. L., Chia J.M., Brenner S., Aparicio S., Venkatesh B. Fugu genome analysis provides evidence for a whole-genome duplication early during the evolution of ray-finned fishes. Molecular Biology and Evolution 2004; 21:1146-1151.
107. Jaillon 0., Aury J. M., Brunet F., Petit J. L., Stange-Thomann N., Mauceli E., Bouneau L., Fischer C., Ozouf-Costaz C., Bernot A., Nicaud S., Jaffe D., Fisher S., Lutfalla G., Dossat C., Segurens B., Dasilva C., Salanoubat M., Levy M., Boudet N., Castellano S., Anthouard V., Jubin C., Castelli V., Katinka M., Vacherie B., Biemont C., Skalli Z., Cattolico L., Poulain J., De Berardinis V., Cruaud C., Duprat S., Brottier P., Coutanceau J. P., Gouzy J., Parra G., Lardier G., Chapple C., McKernan K. J., McEwan P., Bosak S., Kellis M., Volff J.N., Guigo R., Zody M.C., Mesirov J., Lindblad-Toh K., Birren B., Nusbaum C., Kahn D., Robinson-Rechavi M., Laudet V., Schachter V., Quetier F., Saurin W., Scarpelli C., Wincker P. Lander E. S., Weissenbach J., Roest Crollius H. Genome duplication in the teleost fish Tetraodon nigroviridis reveals the early vertebrate proto-karyotype. Nature 2004; 431:946-957.
108. Liu R. Z., Sun Q., Thisse C., Thisse B., Wright J. M., Denovan-Wright E. M.. The cellular retinol-binding protein genes are duplicated and differentially transcribed in the developing and adult zebrafish (Danio rerio) (vol 22, pg 469,2005). Molecular Biology and Evolution 2005; 22:1157-1157.
109. Kleinjan D.A., Bancewicz R. M., Gautier P., Dahm R., Schonthaler H..B.,. Damante G., Seawright A., Hever A.M., Yeyati P. L., van Heyningen V., Coutinho P. Subfunctionalization of duplicated zebrafish pax6 genes by cis-regulatory divergence. PLoS Genet 2008; 4:e29.
110. Volff J.N. Genome evolution and biodiversity in teleost fish. Heredity 2005; 94:280-294.
111. Semon M., Wolfe K. H. Consequences of genome duplication. Curr Opin Genet Dev 2007; 17:505-512.
112. Kuersten S., Goodwin E. B. The power of the 3'UTR:Translational control and development. Nature Reviews Genetics 2003; 4:626-637.
113. Dean K. A., Aggarwal A. K., Wharton R. P. Translational repressors in Drosophila. Trends in Genetics 2002; 18:572-577.
114. Sonoda J., Wharton R. P. Recruitment of Nanos to hunchback mRNA by Pumilio. Genes & Development 1999; 13:2704-2712.
115. Sonoda J., Wharton R. P. Drosophila brain tumor is a translational repressor. Genes & Development 2001; 15:762-773.
116. Wharton R. P., Struhl G. RNA regulatory elements mediate control of drosophila body pattern by the posterior morphogen nanos. Cell 1991; 67:955-967.
117. Murata Y., Wharton R. P. Binding of pumilio to maternal hunchback messenger-RNA Is required for posterior patterning in drosophila embryos. Cell 1995; 80:747-756.
118. Bergsten S.E., Gavis E. R. Role for mRNA localization in translational activation but not spatial restriction of nanos RNA. Development 1999; 126:659-669.
119. Ephrussi A., Dickinson L. K., Lehmann R. Oskar organizes the germ plasm and directs localization of the posterior determinant nanos. Cell 1991; 66:37-50.
120. Gavis E. R., Lehmann R. Localization of nanos RNA controls embryonic polarity. Cell 1992; 71:301-313.
121. Smith J. L., Wilson J. E., Macdonald P.M. Overexpression of oskar directs ectopic activation of nanos and presumptive pole cell-formation in drosophila embryos. Cell 1992; 70:849-859.
122. Dahanukar A., Walker J. A., Wharton R. P. Smaug, a novel RNA-binding protein that operates a translational switch in Drosophila. Molecular Cell 1999; 4:209-218.
123. Smibert C. A., Lie Y. S., Shillinglaw W., Henzel W. J., Macdonald P. M. Smaug, a novel and conserved protein, contributes to repression of nanos mRNA translation in vitro. Rna-a Publication of the Rna Society 1999; 5:_1535-1547.
124. Smibert C. A., Wilson J. E., Kerr K., Macdonald P.M. smaug protein represses translation of unlocalized nanos mRNA in the Drosophila embryo. Genes & Development 1996; 10:2600-2609.
125. Rougvie A. E. Control of developmental timing in animals. Nature Reviews Genetics 2001; 2:690-701.
126. Slack F. J., Basson M., Liu Z. C., Ambros V., Horvitz H. R., Ruvkun G. The lin-41 RBCC gene acts in the C-elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor. Molecular Cell 2000; 5:659-669.
127. Newman A. P., Inoue T., Wang M. Q., Sternberg P. W. The Caenorhabditis elegans heterochronic gene lin-29 coordinates the vulval-uterine-epidermal connections. Current Biology 2000; 10: 1479-1488.