生殖隔離造成物種形成的機制為演化生物學研究的重大挑戰之一，關於物種間生殖隔離的分子機制，目前發現部分相關的基因被發現。然而，這些基因的正常功能為何，如何於物種間產生功能的改變或差異，進而造成生物種間的隔離機制，對於演化學者而言仍是相當有趣的問題。為了解開這些問題，本論文利用模里西斯果蠅及擬黃果蠅雜交種中發現的雜交雄性不孕基因Odysseus (OdsH) 為研究題材，結合果蠅的分子及遺傳技術，以研究OdsH在不同物種間的功能及遺傳機制。利用轉殖基因的遺傳分析，本研究證實OdsH會影響雜交雄果蠅的精子發育，進而造成雄果蠅不孕。黃果蠅的研究顯示，OdsH 與早期精細胞的生成分化有關，且認為影響細胞分化的機制為導致雜交雄果蠅的精子發育缺陷的主因。本研究於果蠅科進行OdsH及其祖先型基因unc-4的序列及表現分析，認為於黃果蠅種亞群中，OdsH可能保留unc-4部份功能或衍伸出新功能，造成其於雄性生殖系統的表現。本研究提供了一個重複基因與種化機制可能的關聯性，雄性快速演化基因對於雜交不孕機制的確扮演重要的角色，精細胞分裂為造成雜交雄果蠅不孕的主要原因。

ADAMS, M. D., S. E. CELNIKER, R. A. HOLT, C. A. EVANS, J. D. GOCAYNE et al., 2000 The genome sequence of Drosophila melanogaster. Science 287: 2185-2195.
AYYAR, S., J. JIANG, A. COLLU, H. WHITE-COOPER and R. A. WHITE, 2003 Drosophila TGIF is essential for developmentally regulated transcription in spermatogenesis. Development 130: 2841-2852.
BAKER, R. J., and J. W. BICKHAM, 1986 Speciation by monobrachial centric fusions. Proc Natl Acad Sci U S A 83: 8245-8248.
BANY, I. A., M. Q. DONG and M. R. KOELLE, 2003 Genetic and cellular basis for acetylcholine inhibition of Caenorhabditis elegans egg-laying behavior. J Neurosci 23: 8060-8069.
BARBASH, D. A., P. AWADALLA and A. M. TARONE, 2004 Functional divergence caused by ancient positive selection of a Drosophila hybrid incompatibility locus. PLoS Biol 2: e142.
BARBASH, D. A., D. F. SIINO, A. M. TARONE and J. ROOTE, 2003 A rapidly evolving MYB-related protein causes species isolation in Drosophila. Proc Natl Acad Sci U S A 100: 5302-5307.
BAYES, J. J., and H. S. MALIK, 2009 Altered heterochromatin binding by a hybrid sterility protein in Drosophila sibling species. Science 326: 1538-1541.
BOLKAN, B. J., R. BOOKER, M. L. GOLDBERG and D. A. BARBASH, 2007 Developmental and cell cycle progression defects in Drosophila hybrid males. Genetics 177: 2233-2241.
BOYLE, M., C. WONG, M. ROCHA and D. L. JONES, 2007 Decline in self-renewal factors contributes to aging of the stem cell niche in the Drosophila testis. Cell Stem Cell 1: 470-478.
BRIDEAU, N. J., H. A. FLORES, J. WANG, S. MAHESHWARI, X. WANG et al., 2006 Two Dobzhansky-Muller genes interact to cause hybrid lethality in Drosophila. Science 314: 1292-1295.
CATRON, D. J., and M. A. NOOR, 2008 Gene expression disruptions of organism versus organ in Drosophila species hybrids. PLoS One 3: e3009.
CHAKIR, M., A. CHAFIK, B. MORETEAU, P. GIBERT and J. R. DAVID, 2002 Male sterility thermal thresholds in Drosophila: D. simulans appears more cold-adapted than its sibling D. melanogaster. Genetica 114: 195-205.
CHEN, Y.-C., 2003 Sequence analysis and functional divergence of Odysseus (OdsH) and unc-4, pp. 21-23, Master Thesis, National Tsing Hua University, Hsinchu, Taiwan.
CHEN, Y.-L., 2005 Functional diversity of Odysseus (OdsH) and its role in spermatogenesis, pp. 11-52, Master Thesis, National Tsing Hua University, Hsinchu, Taiwan.
CHENG, J., N. TURKEL, N. HEMATI, M. T. FULLER, A. J. HUNT et al., 2008 Centrosome misorientation reduces stem cell division during ageing. Nature 456: 599-604.
CLARK, A. G., M. B. EISEN, D. R. SMITH, C. M. BERGMAN, B. OLIVER et al., 2007 Evolution of genes and genomes on the Drosophila phylogeny. Nature 450: 203-218.
CLAUSEN, R. E. and T.H. GOODSPEED, 1925 Interspecific hybridization in Nicotiana. II. A tetraploid glutinosa-Tabacum hybrid, and experimental verification of Winge's hypotheses. Genetics 10: 279-284
COYNE, J., and H. ORR, 1989 Patterns of speciation in Drosophila. Evolution 43: 362-381.
COYNE, J., and H. ORR, 1997 ''Patterns of speciation in Drosophila'' revisited. Evolution 51: 295-303.
COYNE, J. A., 1984 Genetic basis of male sterility in hybrids between two closely related species of Drosophila. Proc Natl Acad Sci U S A 81: 4444-4447.
COYNE, J. A., and H. A. ORR, 2004 Speciation. Sinaure Associated, Inc, Sunderland, MA.
CZERNY, T., G. HALDER, U. KLOTER, A. SOUABNI, W. J. GEHRING et al., 1999 twin of eyeless, a second Pax-6 gene of Drosophila, acts upstream of eyeless in the control of eye development. Mol Cell 3: 297-307.
DAVID, J. R., L. O. ARARIPE, M. CHAKIR, H. LEGOUT, B. LEMOS et al., 2005 Male sterility at extreme temperatures: a significant but neglected phenomenon for understanding Drosophila climatic adaptations. J Evol Biol 18: 838-846.
DAVIS, G. K., C. A. JARAMILLO and N. H. PATEL, 2001 Pax group III genes and the evolution of insect pair-rule patterning. Development 128: 3445-3458.
DE ROSA, R., J. K. GRENIER, T. ANDREEVA, C. E. COOK, A. ADOUTTE et al., 1999 Hox genes in brachiopods and priapulids and protostome evolution. Nature 399: 772-776.
DOBZHANSKY, T., 1936 Studies on hybrid sterility. II. Localization of sterility factors in Drosophila psrudoobscura hybrids. Genetics 21: 113-135.
ELLISON, C. K., O. NIEHUIS and J. GADAU, 2008 Hybrid breakdown and mitochondrial dysfunction in hybrids of Nasonia parasitoid wasps. J Evol Biol 21: 1844-1851.
FABRIZIO, J. J., G. HIME, S. K. LEMMON and C. BAZINET, 1998 Genetic dissection of sperm individualization in Drosophila melanogaster. Development 125: 1833-1843.
FERREE, P. M., and D. A. BARBASH, 2009 Species-specific heterochromatin prevents mitotic chromosome segregation to cause hybrid lethality in Drosophila. PLoS Biol 7: e1000234.
FISHER, R. A., 1935 The Sheltering of lethals. Am Nat 69: 446-455.
FORCE, A., M. LYNCH, F. B. PICKETT, A. AMORES, Y. L. YAN et al., 1999 Preservation of duplicate genes by complementary, degenerative mutations. Genetics 151: 1531-1545.
FROHMAN, M. A., 1993 Rapid amplification of complementary DNA ends for generation of full-length complementary DNAs: thermal RACE. Methods Enzymol 218: 340-356.
FULLER, M. T., 1993 Spermatogenesis, pp. 71-147 in The Development of Drosophila melanogaster. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
FULLER, M. T., 1998 Genetic control of cell proliferation and differentiation in Drosophila spermatogenesis. Semin Cell Dev Biol 9: 433-444.
FULLER, M. T., and A. C. SPRADLING, 2007 Male and female Drosophila germline stem cells: two versions of immortality. Science 316: 402-404.
GEHRING, W. J., M. AFFOLTER and T. BURGLIN, 1994 Homeodomain proteins. Annu Rev Biochem 63: 487-526.
GONCZY, P., E. MATUNIS and S. DINARDO, 1997 bag-of-marbles and benign gonial cell neoplasm act in the germline to restrict proliferation during Drosophila spermatogenesis. Development 124: 4361-4371.
HALDANE, J. B. S., 1933 The part played by recurrent mutation in evolution. Am Nat 67: 5-9.
HARRISON, J. S., and R. S. BURTON, 2006 Tracing hybrid incompatibilities to single amino acid substitutions. Mol Biol Evol 23: 559-564.
HENSE, W., J. F. BAINES and J. PARSCH, 2007 X chromosome inactivation during Drosophila spermatogenesis. PLoS Biol 5: e273.
HOLLAND, P. W., J. GARCIA-FERNANDEZ, N. A. WILLIAMS and A. SIDOW, 1994 Gene duplications and the origins of vertebrate development. Dev Suppl: 125-133.
HUANG, C.-F., 2003 Genetic analysis of hybrid male sterile gene, Odysseus (OdsH), in Drosophila, pp. 34-37, Master Thesis, National Tsing Hua University, Hsinchu, Taiwan.
KIGER, A. A., D. L. JONES, C. SCHULZ, M. B. ROGERS and M. T. FULLER, 2001 Stem cell self-renewal specified by JAK-STAT activation in response to a support cell cue. Science 294: 2542-2545.
KOPP, A., 2006 Basal relationships in the Drosophila melanogaster species group. Mol Phylogenet Evol 39: 787-798.
LEE, H. Y., J. Y. CHOU, L. CHEONG, N. H. CHANG, S. Y. YANG et al., 2008 Incompatibility of nuclear and mitochondrial genomes causes hybrid sterility between two yeast species. Cell 135: 1065-1073.
LI, W.-H., and D. GRAUR, 1997 Fundamentals of Molecular Evolution. Sinauer Associates , Inc., MA.
LIN, T. Y., S. VISWANATHAN, C. WOOD, P. G. WILSON, N. WOLF et al., 1996 Coordinate developmental control of the meiotic cell cycle and spermatid differentiation in Drosophila males. Development 122: 1331-1341.
LONG, M., E. BETRAN, K. THORNTON and W. WANG, 2003 The origin of new genes: glimpses from the young and old. Nat Rev Genet 4: 865-875.
LYNCH, M., and J. S. CONERY, 2000 The evolutionary fate and consequences of duplicate genes. Science 290: 1151-1155.
LYNCH, M., and A. FORCE, 2000 The probability of duplicate gene preservation by subfunctionalization. Genetics 154: 459-473.
MANNERVIK, M., NIBU, Y., ZHANG, H., LEVINE, M., 1999 Transcriptional coregulators in development. Science 284: 606-609.
MARKOW, T. A., L. K. REED and E. S. KELLEHER, 2007 Sperm fate and function in reproductive isolation in Drosophila. Soc Reprod Fertil Suppl 65: 155-173.
MASLY, J. P., C. D. JONES, M. A. NOOR, J. LOCKE and H. A. ORR, 2006 Gene transposition as a cause of hybrid sterility in Drosophila. Science 313: 1448-1450.
MAYR, E., 1963 Animal Species and Evolution. The Belknap press, Combridge, MA.
MICHALAK, P., and M. A. NOOR, 2004 Association of misexpression with sterility in hybrids of Drosophila simulans and D. mauritiana. J Mol Evol 59: 277-282.
MIHOLA, O., Z. TRACHTULEC, C. VLCEK, J. C. SCHIMENTI and J. FOREJT, 2009 A mouse speciation gene encodes a meiotic histone H3 methyltransferase. Science 323: 373-375.
MILLER, D. M., M. M. SHEN, C. E. SHAMU, T. R. BURGLIN, G. RUVKUN et al., 1992 C. elegans unc-4 gene encodes a homeodomain protein that determines the pattern of synaptic input to specific motor neurons. Nature 355: 841-845.
MINAMI, R., M. WAKABAYASHI, S. SUGIMORI, K. TANIGUCHI, A. KOKURYO et al., 2012 The homeodomain protein defective proventriculus is essential for male accessory gland development to enhance fecundity in Drosophila. PLoS One 7: e32302.
MOEHRING, A. J., K. C. TEETER and M. A. NOOR, 2007 Genome-wide patterns of expression in Drosophila pure species and hybrid males. II. Examination of multiple-species hybridizations, platforms, and life cycle stages. Mol Biol Evol 24: 137-145.
MULLER, H. J., 1940 Bearing of the Drosophila work on systematics., pp. 185-268 in The New Systematics, edited by J. S. H. (ED.). Clarendon Press, Oxford.
MULLER, H. J., 1942 Isolating mechanisms, evolution and temperature. Biol. Symp. 6: 71-125.
MUNTZING, A., 1930 Uber Chromosomenvermehrung in Galeopsis-Kreuzungen und ihre phylogenetische Bedeutung. Hereditas 14: 153-172.
O'NEILL, S. L., and T. L. KARR, 1990 Bidirectional incompatibility between conspecific populations of Drosophila simulans. Nature 348: 178-180.
OHNO, S., 1970 Evolution by Gene Duplication. Springer-Verlag, New York.
ORR, H. A., 1995 The population genetics of speciation: the evolution of hybrid incompatibilities. Genetics 139: 1805-1813.
ORTIZ-BARRIENTOS, D., B. A. COUNTERMAN and M. A. NOOR, 2007 Gene expression divergence and the origin of hybrid dysfunctions. Genetica 129: 71-81.
PARISI, M., R. NUTTALL, D. NAIMAN, G. BOUFFARD, J. MALLEY et al., 2003 Paucity of genes on the Drosophila X chromosome showing male-biased expression. Science 299: 697-700.
PATEL, N. H., 1996 In situ hybridization to whole-mount Drosophila embryos., pp. 357-369 in A Laboratory Guide to RAN: Isolation, Analysis, and Synthesis, edited by K. P. A. Wiley-Liss, New York.
PEREZ, D. E., and C.-I. WU, 1995 Further characterization of the Odysseus locus of hybrid sterility in Drosophila: one gene is not enough. Genetics 140: 201-206.
PEREZ, D. E., C.-I. WU, N. A. JOHNSON and M.-L. WU, 1993 Genetics of reproductive is isolation in the Drosophila simulans clade: DNA marker-assisted mapping and characterization of a hybrid-male sterility gene, Odysseus (Ods). Genetics 134: 261-275.
PRESGRAVES, D. C., L. BALAGOPALAN, S. M. ABMAYR and H. A. ORR, 2003 Adaptive evolution drives divergence of a hybrid inviability gene between two species of Drosophila. Nature 423: 715-719.
PRICE, A. L., and N. H. PATEL, 2008 Investigating divergent mechanisms of mesoderm development in arthropods: the expression of Ph-twist and Ph-mef2 in Parhyale hawaiensis. J Exp Zoolog B Mol Dev Evol 310: 24-40.
PRINCE, V., 2002 The Hox Paradox: More complex(es) than imagined. Dev Biol 249: 1-15.
REED, L. K., and T. A. MARKOW, 2004 Early events in speciation: polymorphism for hybrid male sterility in Drosophila. Proc Natl Acad Sci U S A 101: 9009-9012.
RIESEBERG, L. H., and J. H. WILLIS, 2007 Plant speciation. Science 317: 910-914.
ROHMER, C., J. R. DAVID, B. MORETEAU and D. JOLY, 2004 Heat induced male sterility in Drosophila melanogaster: adaptive genetic variations among geographic populations and role of the Y chromosome. J Exp Biol 207: 2735-2743.
RYLETT, C. M., M. J. WALKER, G. J. HOWELL, A. D. SHIRRAS and R. E. ISAAC, 2007 Male accessory glands of Drosophila melanogaster make a secreted angiotensin I-converting enzyme (ANCE), suggesting a role for the peptide-processing enzyme in seminal fluid. J Exp Biol 210: 3601-3606.
SANTEL, A., T. WINHAUER, N. BLUMER and R. RENKAWITZ-POHL, 1997 The Drosophila don juan (dj) gene encodes a novel sperm specific protein component characterized by an unusual domain of a repetitive amino acid motif. Mech Dev 64: 19-30.
SAWAMURA, K., J. ROOTE, C. I. WU and M. T. YAMAMOTO, 2004 Genetic complexity underlying hybrid male sterility in Drosophila. Genetics 166: 789-796.
SCHARTL, M., U. HORNUNG, H. GUTBROD, J. N. VOLFF and J. WITTBRODT, 1999 Melanoma loss-of-function mutants in Xiphophorus caused by Xmrk-oncogene deletion and gene disruption by a transposable element. Genetics 153: 1385-1394.
SINGH, S. R., X. CHEN and S. X. HOU, 2005 JAK/STAT signaling regulates tissue outgrowth and male germline stem cell fate in Drosophila. Cell Res 15: 1-5.
SINGH, S. R., and S. X. HOU, 2008 Immunohistological techniques for studying the Drosophila male germline stem cell. Methods Mol Biol 450: 45-59.
SMITH, S. T., and J. B. JAYNES, 1996 A conserved region of engrailed, shared among all en-, gsc-, Nk1-, Nk2- and msh-class homeoproteins, mediates active transcriptional repression in vivo. Development 122: 3141-3150.
SPRADLING, A., D. DRUMMOND-BARBOSA and T. KAI, 2001 Stem cells find their niche. Nature 414: 98-104.
SULLOWAY, F. J., 1979 Geographic isolation in Darwin's thinking: the vicissitudes of a crucial idea. Stud Hist Biol 3: 23-65.
SUN, S., 2003 Functional analysis of the hybrid male sterility gene Odysseus in Drosophila, pp. 15-16, Ph.D Thesis. University of Chicago, Chicago.
SUN, S., C.-T. TING and C.-I. WU, 2004 The normal function of a speciation gene, Odysseus, and its hybrid sterility effect. Science 305: 81-83.
SWANSON, W. J., A. G. CLARK, H. M. WALDRIP-DAIL, M. F. WOLFNER and C. F. AQUADRO, 2001 Evolutionary EST analysis identifies rapidly evolving male reproductive proteins in Drosophila. Proc Natl Acad Sci USA 98: 7375-7379.
TABUCHI, K., S. YOSHIKAWA, Y. YUASA, K. SAWAMOTO and H. OKANO, 1998 A novel Drosophila paired-like homeobox gene related to Caenorhabditis elegans unc-4 is expressed in subsets of postmitotic neurons and epidermal cells. Neurosci Lett 257: 49-52.
TANG, S., and D. C. PRESGRAVES, 2009 Evolution of the Drosophila nuclear pore complex results in multiple hybrid incompatibilities. Science 323: 779-782.
TAO, Y., J. P. MASLY, L. ARARIPE, Y. KE and D. L. HARTL, 2007 A sex-ratio meiotic drive system in Drosophila simulans. I: an autosomal suppressor. PLoS Biol 5: e292.
TAO, Y., Z. B. ZENG, J. LI, D. L. HARTL and C. C. LAURIE, 2003 Genetic dissection of hybrid incompatibilities between Drosophila simulans and D. mauritiana. II. Mapping hybrid male sterility loci on the third chromosome. Genetics 164: 1399-1418.
TING, C.-T., S.-C. TSAUR, S. SUN, W. E. BROWNE, Y.-C. CHEN et al., 2004 Gene duplication and speciation in Drosophila: evidence from the Odysseus locus. Proc Natl Acad Sci USA 101: 12232-12235.
TING, C.-T., S.-C. TSAUR and C.-I WU, 2000 The phylogeny of closely related species as revealed by the genealogy of a speciation gene, Odysseus. Proc Natl Acad Sci USA 97: 5313-5316.
TING, C.-T., S.-C. TSAUR, M.-L. WU and C.-I WU, 1998 A rapidly evolving homeobox at the site of a hybrid sterility gene. Science 282: 1501-1504.
TOKUYASU, K. T., 1975 Dynamics of spermiogenesis in Drosophila melanogaster. VI. Significance of "onion" nebenkern formation. J Ultrastruct Res 53: 93-112.
TOKUYASU, K. T., W. J. PEACOCK and R. W. HARDY, 1972 Dynamics of spermiogenesis in Drosophila melanogaster. I. Individualization process. Z Zellforsch Mikrosk Anat 124: 479-506.
TRUE, J. R., B. S. WEIR and C. C. LAURIE, 1996 A genome-wide survey of hybrid incompatibility factors by the introgression of marked segments of Drosophila mauritiana chromosomes into Drosophila simulans. Genetics 142: 819-837.
TULINA, N., and E. MATUNIS, 2001 Control of stem cell self-renewal in Drosophila spermatogenesis by JAK-STAT signaling. Science 294: 2546-2549.
WAKIMOTO, B. T., D. L. LINDSLEY and C. HERRERA, 2004 Toward a comprehensive genetic analysis of male fertility in Drosophila melanogaster. Genetics 167: 207-216.
WATANABE, T. K., 1979 A gene that rescues the lethal hybrids between Drosophila melanogaster and D. simulans. Jpn. J. Genet. 54: 325-331.
WATT, F. M., and B. L. HOGAN, 2000 Out of Eden: stem cells and their niches. Science 287: 1427-1430.
WEN, S. Y., K. SHIMADA, K. KAWAI and M. J. TODA, 2006 Strong purifying selection on the Odysseus gene in two clades of sibling species of the Drosophila montium species subgroup. J Mol Evol 62: 659-662.
WHITE-COOPER, H., 2004 Spermatogenesis: analysis of meiosis and morphogenesis. Methods Mol Biol 247: 45-75.
WHITE-COOPER, H., L. ALPHEY and D. M. GLOVER, 1993 The cdc25 homologue twine is required for only some aspects of the entry into meiosis in Drosophila. J Cell Sci 106 ( Pt 4): 1035-1044.
WHITE-COOPER, H., M. A. SCHAFER, L. S. ALPHEY and M. T. FULLER, 1998 Transcriptional and post-transcriptional control mechanisms coordinate the onset of spermatid differentiation with meiosis I in Drosophila. Development 125: 125-134.
WHITE, J. G., E. SOUTHGATE and J. N. THOMSON, 1992 Mutations in the Caenorhabditis elegans unc-4 gene alter the synaptic input to ventral cord motor neurons. Nature 355: 838-841.
WINNIER, A. R., J. Y. MEIR, J. M. ROSS, N. TAVERNARAKIS, M. DRISCOLL et al., 1999 UNC-4/UNC-37-dependent repression of motor neuron-specific genes controls synaptic choice in Caenorhabditis elegans. Genes Dev 13: 2774-2786.
Winge, O, 1917 The chromosomes: Their number and general importance. C R. Trav. Lab. Carlsberg 13:131-275.
WOLFNER, M. F., 2002 The gifts that keep on giving: physiological functions and evolutionary dynamics of male seminal proteins in Drosophila. Heredity 88: 85-93.
WU, C.-I., and C.-T. TING, 2004 Genes and speciation. Nat Rev Genet 5: 114-122.
WU, C. I., and A. W. DAVIS, 1993 Evolution of postmating reproductive isolation: the composite nature of Haldane's rule and its genetic bases. Am Nat 142: 187-212.
WU, C. I., and M. F. PALOPOLI, 1994 Genetics of postmating reproductive isolation in animals. Annu Rev Genet 28: 283-308.
YAMASHITA, Y. M., M. T. FULLER and D. L. JONES, 2005 Signaling in stem cell niches: lessons from the Drosophila germline. J Cell Sci 118: 665-672.
YAMASHITA, Y. M., D. L. JONES and M. T. FULLER, 2003 Orientation of asymmetric stem cell division by the APC tumor suppressor and centrosome. Science 301: 1547-1550.
YAMASHITA, Y. M., A. P. MAHOWALD, J. R. PERLIN and M. T. FULLER, 2007 Asymmetric inheritance of mother versus daughter centrosome in stem cell division. Science 315: 518-521.