The Bithorax Complex: The First Fifty Years

  • Edward B. Lewis


Genetics is a discipline that has successfully used abstractions to attack many of the most important problems of biology, including the study of evolution and how animals and plants develop. The power of genetics to benefit mankind was first recognized by the award of the Nobel Prize in physiology or medicine in 1933 to T. H. Morgan. In the 23 years that had intervened between the time Morgan introduced Drosophila as a new organism for the study of genetics and the award of the Prize, he and his students, especially, A. H. Sturtevant, C. B. Bridges and H. J. Muller, had vastly extended the laws of Mendel as the result of a host of discoveries, to mention only a few: that the genes (Mendel’s factors) are arranged in a linear order and can be placed on genetic maps, that they mutate in forward and reverse directions, that they can exist in many forms, or alleles, and that their functioning can depend upon their position. Purely on the basis of breeding experiments, these early workers were able to deduce the existence of inversions and duplications, for example, before it became possible to demonstrate them cytologically. The list of their achievements is a long one and one that has been put into historical perspective by Sturtevant in A History of Genetics (1).


BITHORAX Complex Land Chromosome 
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  1. 1.
    Sturtevant AH. A History of Genetics. Harper & Row New York 1965.Google Scholar
  2. 2.
    Muller HJ. Artificial transmutation of the gene. Science 1927; 66:84–87.Google Scholar
  3. 3.
    Nusslein-Volhard C, Wieschaus E. Mutations affecting segment number and polarity in Drosophila. Nature 1980;287:795–801.PubMedCrossRefGoogle Scholar
  4. 4.
    Johannsen W. The Genotype Conception of Heredity. The American Naturalist 1911; XLV (March): 129–159.Google Scholar
  5. 5.
    Sturtevant AH. The effects of unequal crossing over at the Bar locus in Drosophila. Genetics 1925; 10:117–147.PubMedGoogle Scholar
  6. 6.
    Bridges CB. The Bar ‘gene’: a duplication. Science 1936;83:210–211.PubMedCrossRefGoogle Scholar
  7. 7.
    Muller HJ, Prokofyeva-Belgovskaya AA, Kossikov KV. Unequal crossing-over in the Bar mutant as a result of duplication of a minute chromosome section. Comptes Rendus (Doklady) el l’Academie des Sciences del l’URSS 1936;1:87–88.Google Scholar
  8. 8.
    Wright S. The Dominance of Bar over Infra-Bar in Drosophila. The American Naturalist 1929;63(September-October):479–480.CrossRefGoogle Scholar
  9. 9.
    Bridges CB. Salivary chromosome maps with a key to the banding of the chromosomes of Drosophila melanogaster. Journal of Heredity 1935;26: 60–64.Google Scholar
  10. 10.
    Oliver CP. A reversion to wild-type associated with crossing over in Drosophila melanogaster. Proceedings of the National Academy of Sciences USA 1940:26:452–CrossRefGoogle Scholar
  11. 11.
    Lewis EB. Pseudoallelism and gene evolution. Cold Spring Harbor Symposium of Quantitative Biology 1951;16:159–174.CrossRefGoogle Scholar
  12. 12.
    Lewis EB. Star-recessive, a spontaneous mutation in Drosophila melanogaster. Proceedings of the Minnesota Academy of Sciences 1939;7:23–26.Google Scholar
  13. 13.
    Lewis EB. Another case of unequal crossing over in Drosophila melanogaster. Proceedings of the National Academy of Sciences USA 1941;27:31–34.CrossRefGoogle Scholar
  14. 14.
    Lewis EB. The Star and asteroid loci in Drosophila melanogaster. Genetics 1942;27:153–154.Google Scholar
  15. 15.
    Lewis EB. A Genetic and Cytological Analysis of a Tandem Duplication and its Included Loci in Drosophila melanogaster [Ph.D.]. California Institute of Technology. 1942.Google Scholar
  16. 16.
    Lewis EB. The relation repeats to position effect in Drosophila melanogaster. Genetics 1945;30:137–166.PubMedGoogle Scholar
  17. 17.
    Hayes W. The Genetics of Bacteria and Their Viruses: Studies in Basic Genetics and Molecular Biology. (2nd ed.) John Wiley & Sons Inc. New York, 1968.Google Scholar
  18. 18.
    Lewis EB. Homeosis: the first 100 years. Trends in Genetics 1994;(10):341–343.PubMedCrossRefGoogle Scholar
  19. 19.
    Bridges CB. The Mutants of Drosophila melanogaster. The Lord Baltimore Press Baltimore, MD 1944:257. (Brehme KS, ed.) Carnegie Institution of Washington Publication 552.Google Scholar
  20. 20.
    Green MM, Green KC. Crossing-over between alleles at the lozenge locus in Drosophila melanogaster. Proceedings of the National Academy of Sciences USA 1949;35:586–591.CrossRefGoogle Scholar
  21. 21.
    Lewis EB. Pseudoallelism and the gene concept. Proceedings of the 9th International Congress of Genetics, 1954;1:100–105.Google Scholar
  22. 22.
    Lewis EB. Regulation in cis and trans of the bithorax gene complex in Drosophila. Journal of Cellular Biochemistry 1984;s 8B:6.Google Scholar
  23. 23.
    Lewis EB. Some aspects of pseudoalleism. American Naturalist 1955;89:73–89.CrossRefGoogle Scholar
  24. 24.
    Brink RA. Are the chromosomes aggregates of groups of physiologically interdependent genes? American Naturalist 1932;66:444–451.CrossRefGoogle Scholar
  25. 25.
    Kaufman TC, Lewis R, Wakimoto B. Cytogenetic analysis of chromosome 3 in Drosophila melanogaster, the homeotic gene complex in polytene chromosomal interval 84A,B. Genetics 1980;94:115–133.PubMedGoogle Scholar
  26. 26.
    Lewis EB. The theory and application of a new method of detecting chromosomal rearrangements in Drosophila melanogaster. American Naturalist 1954;88:225–239.CrossRefGoogle Scholar
  27. 27.
    Gelbart WM. Synapsis-dependent allelic complementation at the decapentaplegic gene-complex in Drosophila melanogaster. Proceedings of the National Academy of Sciences, USA 1982;79(8):2636–2640.CrossRefGoogle Scholar
  28. 28.
    Leiserson WM, Bonini N.M., Benzer S. Transvection at the eyes absent gene of Drosophila. Genetics 1994;138(4):1171–1179.PubMedGoogle Scholar
  29. 29.
    Lewis EB. A gene complex controlling segmentation in Drosophila. Nature 1978;276:565–570.PubMedCrossRefGoogle Scholar
  30. 30.
    Celniker SE, Lewis EB. Transabdominal: a dominantmutant of the bithorax complex produces a sexually dimorphic segmental transformation in Drosophila. Genes and Development 1987;1:111–123.PubMedCrossRefGoogle Scholar
  31. 31.
    Judd BH, Shen MW, Kaufman TC. The anatomy and function of a sement of the X chromosome of Drosophila melanogaster. Genetics 1972;71:139–156.PubMedGoogle Scholar
  32. 32.
    Gans M. Genetic and physiological study of mutant Z of Drosophila melanogaster. Bulletin Biologique de France et de Belgique 1953; 28:1–90.Google Scholar
  33. 33.
    Benson M, Pirrotta V. The product of the Drosophila-zeste gene binds ot specific DNA-sequences in white and Ubx EMBO Journal 1987; 6:1387–1392.PubMedGoogle Scholar
  34. 34.
    Benson M, Pirrotta V. The Drosophila zeste protein binds cooperatively to sites in many gene regulatory regions: implications for transvection and gene regulation EMBO Journal 1988; 7:3907–3915.PubMedGoogle Scholar
  35. 35.
    Bridges C. Specific Suppressors in Drosophila Proceedings of the 6th International Congress of Genetics 1932; 2:12–14.Google Scholar
  36. 36.
    Lewis EB. su2-Hw: suppressor-2-Hairy-wing Drosophila Information Service 1949; 23:59–60.Google Scholar
  37. 37.
    Modolell J, Bender W, Meselson M. Drosophila melanogaster mutations suppressible by the suppressor Hairy-wing are insertions of a 7.3-kilobase mobile element Proceedings of the National Academy of Sciences USA 1983; 80:1678–1682.CrossRefGoogle Scholar
  38. 38.
    Parkhurst SM, Harrison DA, Remington MP, Spana C, Kelly RL, Coyne RS, Corces VG. The Drosophila su(Hw) gene, which controls the phenotypic effect of the gypsy transposable element, encodes a putative DNA-binding protein Genes & Development 1988; 2(10):1205–1215.CrossRefGoogle Scholar
  39. 39.
    Parkhurst SM Corces V. G. Mutations at the suppressor of forked locus increase the accumulation of Gypsy-encoded transcripts in Drosophila melanogaster Molecular & Cellular Biology 1986; 6(6):2271–2274.Google Scholar
  40. 40.
    Bender W, Akam M, Karch FA, Beachy PA, Peifer M, Spierer P, Lewis EB, Hogness DS. Molecular genetics of the Bithorax Complex in Drosophila melanogaster Science 1983; 221:23–29.PubMedCrossRefGoogle Scholar
  41. 41.
    Holliday R. A mechanism for gene conversion in fungi Genetic Research 1964; 5:282–304.CrossRefGoogle Scholar
  42. 42.
    Lindsley DL, Grell EH. Genetic Variations of Drosophila melanogaster. Carnegie Institution of Washington Washington D. C., 1968; Publication 627).Google Scholar
  43. 43.
    Lewis EB. Genes and gene complexes. In: Brink RA, ed. Heritage from Mendel. University of Wisconsin Press Madison, Wis. 1967: 17–47.Google Scholar
  44. 44.
    Lewis EB. The pseudoallelism of white and apricot in Drosophila melanogaster Proceedings of the National Academy of Sciences USA 1952; 38:953–961.CrossRefGoogle Scholar
  45. 45.
    Duncan I. The Bithorax Complex Annual Review of Genetics 1987; 21:285–319.PubMedCrossRefGoogle Scholar
  46. 46.
    Lewis EB. Clusters of master control genes regulate the development of higher organisms Journal of the American Medical Association 1992; 267:1524–1531.PubMedCrossRefGoogle Scholar
  47. 47.
    Lewis EB. Genes and developmental pathways American Zoologist 1963; 3:33–56.Google Scholar
  48. 48.
    Morata G, Garcia-Bellido A. Developmental analysis of some mutants of the Bithorax System of Drosophila Wilhelm Roux Archives 1976; 179:125–143.CrossRefGoogle Scholar
  49. 49.
    Lewis EB. Genetic control and regulation of developmental pathways. In: Locke M, sed. Role of Chromosomes in Development. Academic Press Inc. New York: 1964:231–252.Google Scholar
  50. 50.
    Garcia-Bellido A. Genetic control of wing disc development in Drosophila. In: Brenner S, ed. Cell Patterning, Ciba Foundation Symposium. Associated Scientific Publishers, 1975: 161–182.Google Scholar
  51. 51.
    Sanchez-Herrero E, Vernos I, Marco R, Morata G. Genetic organization of Drosophila Bithorax Complex Nature 1985; 313:108–113.PubMedCrossRefGoogle Scholar
  52. 52.
    Tiong S, Bone LM, Whittle JR. Recessive lethalmutations within the Bithorax Complex in Drosophila Molecular and General Genetics 1985; 200:335–342.PubMedCrossRefGoogle Scholar
  53. 53.
    Karch F, Weiffenbach B, Peifer M, Bender W, Duncan I, Celniker S, Crosby M, Lewis EB. The abdominal region of the Bithorax Complex Cell 1985; 43:81–96.PubMedCrossRefGoogle Scholar
  54. 54.
    Lewis EB. Regulation of the genes of the Bithorax Complex in Drosophila Cold Spring Harbor Symposium of Quantitative Biology 1985; 50: 155–164.CrossRefGoogle Scholar
  55. 55.
    Lewis PH. Pc: Polycomb. Drosophila Information Service 1949; 21:69.Google Scholar
  56. 56.
    Duncan I. Polycomblike: A gene that appears to be required for the normal expression of the bithorax and Antennapedia gene complexes of Drosophila melanogaster Genetics 1982; 102:49–70.PubMedGoogle Scholar
  57. 57.
    Jurgens G. A group of genes controlling the spatial expression of the bithorax complex in Drosophila Nature 1985; 316:153–155.CrossRefGoogle Scholar
  58. 58.
    Zink B, Paro R. In vivo binding pattern of a trans-regulator of homeotic genes in Drosophila melanogaster Nature 1989; 337:468–471.PubMedCrossRefGoogle Scholar
  59. 59.
    Paro R, Hogness DS. The Polycomb protein shares a homologous domain with a heterochromatinassociated protein of Drosophila Proceedings of the National Academy of Sciences USA 1991; 88:263–267.CrossRefGoogle Scholar
  60. 60.
    Lewis EB. Developmental genetics of the bithorax complex in Drosophila. In: Brown DD, Fox CF, ed. Developmental Biology Using Purified Genes. ICN-UCLA Symposia on Molecular and Cellular Biology. Keystone, Colorado Academic Press, 1981: 189–208.Google Scholar
  61. 61.
    Ingham P, Whittle JRS. Trithorax: A new homeotic mutation of Drosophila melanogaster causing transformations of abdominal and thoracic imaginal segments Molecular and General Genetics 1980; 179:607–614.CrossRefGoogle Scholar
  62. 62.
    Kuzin B, Tillib S, Sedkov Y, Mizrokhi L, Mazo A. The Drosophila trithorax gene encodes a chromosomal protein and directly regulates the region-specific homeotic gene fork head Genes and Development 1994; 8:2478–2490.PubMedCrossRefGoogle Scholar
  63. 63.
    Stassen MJ, Bailey D, Nelson S, Chinwalla V, Harte PJ. The Drosophila trithorax proteins contain a novel variant of the nuclear receptor-type DNA-binding domain and an ancient conserved motif found in other chromosomal proteins Mechanisms of Development 1995; 52:209–223.PubMedCrossRefGoogle Scholar
  64. 64.
    Kennison JA, Tamkun JW. Dosage-dependent modifiers of Polycomb and Antennapedia mutations in Drosophila Proceedings of the National Academy of Science 1988; 85:8136–8140.CrossRefGoogle Scholar
  65. 65.
    Qian S, Capovilla M, Pirrotta V. The bx region enhancer, a distant cis-control element of the Drosophila Ubx gene and its regulation by hunchback and other segmentation genes EMBO Journal 1991; 10:1415–1425.PubMedGoogle Scholar
  66. 66.
    Bender M, Turner FR, Kaufman TC. A developmental genetic analysis of the gene regulator of postbithorax in Drosophila melanogaster. Developmental Biology 1987; 119:418–432.PubMedCrossRefGoogle Scholar
  67. 67.
    Lewis EB. Genetic control of developmental pathways in Drosophila melanogaster. Proceedings of the 12th International Congress of Genetics. Tokyo, Japan Science Council of Japan, 1968: 96–97.Google Scholar
  68. 68.
    Gloor H. Phänotypus der Heterozygoten bei der unvollständing dominanten, homozygot letalen Mutante Kr (= Krüppel) von Drosophila melanogaster. Arch. Julius Klaus-Stift. Vererbungsforsch. Sozialanthropol. Rassenhyg 1950; 25:38–44.Google Scholar
  69. 69.
    Rosenberg UB, Schroder C, Preiss A, Kienlin A, Cote S, Riede I, Jackle H. Structural homology of the product of the Drosophila Kruppel gene with Xenopus transcription factor IIIA. Nature 1986; 319:336–339.CrossRefGoogle Scholar
  70. 70.
    Schuh R, Aicher W, Gaul U, Cote S, Preiss A, Maier D, Seifert E, Nauber U, Schroder C, Kemler R, Jackle H. A conserved family of nuclear proteins containing structural elements of the finger protein encoded by Kruppel, a Drosophila segmentation gene. Cell 1986; 47:1025–1032.PubMedCrossRefGoogle Scholar
  71. 71.
    Shimell MJ, Simon J, Bender W, O’Connor MB. Enhancer point mutation results in a homeotic transformation in Drosophila. Science 1994; 264(5161):968–971.CrossRefGoogle Scholar
  72. 72.
    O’Connor MB, Binari R, Perkins LA, Bender W. Alernative RNA products from the Ultrabithorax domain of the bithorax complex. EMBO Journal 1988; 7(2):435–445.PubMedGoogle Scholar
  73. 73.
    Kornfeld K, Saint RB, Beachy PA, Harte PJ, Peattie DA, Hogness DS. Structure and expression of a family of Ultrabithorax mRNAs generated by alternative splicing and polyadenylation in Drosophila. Genes and Development 1989; 3:243–258.PubMedCrossRefGoogle Scholar
  74. 74.
    White RAH, Wilcox M. Protein products of the Bithorax Complex in Drosophila. Cell 1984; 39:163–171.PubMedCrossRefGoogle Scholar
  75. 75.
    Beachy PA, Helfand SL, Hogness DS. Segmental distribution of Bithorax Complex proteins during Drosophila development. Nature 1985; 313:545–551.PubMedCrossRefGoogle Scholar
  76. 76.
    Karch F, Bender W, Weiffenbach B. abd-A expression in Drosophila embryos. Genes and Development 1990; 4:1573–1587.PubMedCrossRefGoogle Scholar
  77. 77.
    Sanchez-Herrero E, Crosby MA. The Abdominal-B gene of Drosophila melanogaster, overlapping transcripts exhibit two different spatial distributions. EMBO Journal 1988; 7:2163–2173.PubMedGoogle Scholar
  78. 78.
    Kuziora MA, McGinnis W. Different transcripts of the Drosophila Abd-B gene correlate with distinct genetic sub-functions. EMBO Journal 1988; 7:3233–3244.PubMedGoogle Scholar
  79. 79.
    DeLorenzi M, Ali N, Saari G, Henry C, Wilcox M, Bienz M. Evidence that the Abdominal-B r element function is conferred by a trans-regulatory homeoprotein. EMBO Journal 1988; 7(10):3223–3231.PubMedGoogle Scholar
  80. 80.
    Celniker SE, Keelan DJ, Lewis EB. The molecular genetics of the bithorax complex of Drosophila: characterization of the products of the Abdominal-B domain. Genes and Develo