Chapter 3 Genotype-Phenotype Mapping. Developmental Biology Confronts the Toolkit Paradox

International Review of Cell and Molecular Biology

Volumn 278, Issue C, 2009, Pages 119-148

  Atallah, Joel ^a,b   Larsen, Ellen ^a  

^a UNIVERSITY OF TORONTO   (Canada)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Cell dynamics; Context; Emergent properties; Gene regulation; Gene morphology relationship; Genetic toolkit; Genotype phenotype map; Morphogenesis; Phenotypic diversity; Self organization

Indexed keywords

ANTENNAPEDIA PROTEIN; CELL DNA; NUCLEOTIDE; TRANSCRIPTION FACTOR; UNTRANSLATED RNA;

BIOMEDICINE; CHROMATIN; DNA SEQUENCE; EMBRYO DEVELOPMENT; EVOLUTIONARY DEVELOPMENTAL BIOLOGY; GENE MAPPING; GENE REGULATORY NETWORK; GENETIC CODE; GENETIC CONSERVATION; GENETIC VARIABILITY; GENOTYPE; HOX GENE; HUMAN; MOLECULAR BIOLOGY; MOLECULAR DYNAMICS; MOLECULAR PHYLOGENY; MORPHOGENESIS; NONHUMAN; NUCLEOTIDE SEQUENCE; PHENOTYPE; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION; ANIMAL; DEVELOPMENTAL BIOLOGY; GENE; GENE EXPRESSION REGULATION; PHYSIOLOGY;

ANIMALS; DEVELOPMENTAL BIOLOGY; GENE EXPRESSION REGULATION, DEVELOPMENTAL; GENES; GENOTYPE; HUMANS; PHENOTYPE;

EID: 73349108812     PISSN: 19376448     EISSN: None     Source Type: Book Series    
DOI: 10.1016/S1937-6448(09)78003-7     Document Type: Review

References (138)

1. Ahituv N., Zhu Y., Visel A., Holt A., Afzal V., Pennacchio L.A., et al. Deletion of ultraconserved elements yields viable mice. PLoS Biol. 5 (2007) e234
2. Alvarez-Castro J.M., Le Rouzic A., and Carlborg O. How to perform meaningful estimates of genetic effects. PLoS Genet. 2 (2008) e1000062
3. Andalfatto P. Adaptive evolution of non-coding DNA in Drosophila. Nature 437 (2005) 1149-1152
4. Arrieta M.I., Criado B., Hauspie R., Martinez B., Lobato N., and Lostao C.M. Effects of genetic and environmental factors on the a-b, b-c and c-d interdigital ridge counts. Hereditas 117 (1992) 189-194
5. Ascioti F.A. Four twins for a paradox: on "sensitive" twins and the biological counterpart of the "twin paradox". Chaos 19 (2009) 013128
6. Atallah J., Dworkin I., Cheung U., Greene A., Ing B., Leung L., et al. The environmental and genetic regulation of obake expressivity: morphogenetic fields as evolvable systems. Evol. Dev. 6 (2004) 114-122
7. Atallah J., Liu N.H., Dennis P., Hon A., Godt D., and Larsen E. Cell dynamics and developmental bias in the ontogeny of a complex sexually dimorphic trait. Evol. Dev. 11 (2009) 191-204
8. Atallah J., Liu N.H., Dennis P., Hon A., Godt D., and Larsen E. Developmental constraints and convergent evolution in Drosophila sex comb formation. Evol. Dev. 11 (2009) 205-218
9. Barmina O., and Kopp A. Sex-specific expression of a HOX gene associated with rapid morphological evolution. Dev. Biol. 311 (2007) 277-286
10. Beadle G.W., and Tatum E.L. Genetic control of biochemical reactions in Neurospora. Proc. Natl. Acad. Sci. USA 27 (1941) 499-506
11. Bejerano G., Pheasant M., Makunin I., Stephen S., Kent W.J., Mattick J.S., et al. Ultraconserved elements in the human genome. Science 304 (2004) 1321-1325
12. Bergman A., and Siegal M.L. Evolutionary capacitance as a general feature of complex gene networks. Nature 424 (2003) 549-552
13. Berman B.P., Nibu Y., Pfeiffer B.D., Tomancak P., Celniker S.E., Levine M., et al. Exploiting transcription factor binding site clustering to identify cis-regulatory modules involved in pattern formation in the Drosophila genome. Proc. Natl. Acad. Sci. USA 99 (2002) 757-762
14. Bock I.R., and Wheeler M.R. The Drosophila melanogaster species group. Univ. Tex. Publ. 7213 (1972) 1-102
15. Bray S., and Johnson R.S. Putting the tissue and environmental 'context' into differentiation and gene regulation. Curr. Opin. Genet. Dev. 18 (2008) 395-396
16. Bridges C.B. The Bar "gene" a duplication. Science 83 (1936) 210-211
17. Brosnan C.A., and Voinnet O. The long and the short of noncoding RNAs. Curr. Opin. Cell Biol. 21 (2009) 416-425
18. Bruder C.E.G., Piotrowski A., Gijsbers A.A.C.J., Andersson R., Erickson S., de Stahl T.D., et al. Phenotypically concordant and discordant monozygotic twins display different DNA Copy-Number-Variation profiles. Am. J. Hum. Genet. 82 (2008) 763-771
19. Butte A.J., and Kohane I.S. Creation and implications of a phenome-genome network. Nat. Biotechnol. 24 (2006) 55-62
20. Carroll S.B. Endless Forms Most Beautiful (2005), W.W. Norton & Co., New York
21. Collins F.S., and McKusick V.A. Implications of the Human Genome Project for medical science. JAMA 285 (2001) 540-544
22. Concolino D., Rossi E., Strisciuglio P., Iembo M.A., Giorda R., Ciccone R., et al. Deletion of 760 kb region at 4p16 determines the prenatal and postnatal growth retardation characteristic of Wolf-Hirschhorn syndrome. J. Med. Genet. 44 (2007) 647-650
23. Copeland J.W., Nasiadka A., Dietrich B.H., and Krause H.M. Patterning of the Drosophila embryo by a homeodomain-deleted Ftz polypeptide. Nature 379 (1996) 162-165
24. Darwin C. On the Origin of the Species. first ed. (1859), Harvard University Press, Cambridge
25. Davidson E.H., and Levine M.S. Properties of developmental gene regulatory networks. Proc. Natl. Acad. Sci. USA 105 (2008) 20063-20066
26. Davidson E.H., Rast J.P., Oliveri P., Ransick A., Calestani C., Yuh C., et al. A genomic regulatory network for development. Science 295 (2002) 1669-1678
27. del Rio A., Perez-Jimenez R., Liu R., Roca-Cusachs P., Fernandez J.M., and Sheetz M.P. Stretching single talin rod molecules activates vinculin binding. Science 323 (2009) 638-641
28. De Renzis S., Yu J., Zinzen R., and Wieschaus E. Dorsal ventral pattern of Delta trafficking is established by a Snail-Tom-Neuralized pathway. Dev. Cell 10 (2006) 257-264
29. Duboule D. The rise and fall of Hox gene clusters. Development 134 (2007) 2549-2560
30. Dworkin I. Evidence for canalization of Distal-less function in the leg of Drosophila melanogaster. Evol. Dev. 7 (2005) 89-100
31. Dworkin I. A study of canalization and developmental stability in the sternopleural bristle system of Drosophila melanogaster. Evolution 59 (2005) 1500-1509
32. Dworkin I., Palsson A., Birdsall K., and Gibson G. Evidence that Egfr contributes to cryptic genetic variation for photoreceptor determination in natural populations of Drosophila melanogaster. Curr. Biol. 13 (2003) 1888-1893
33. Ettensohn C.A. Lessons from a gene regulatory network: echinoderm skeletogenesis provides insights into evolution, plasticity and morphogenesis. Development 136 (2009) 11-21
34. Feil R., and Berger F. Convergent evolution of genomic imprinting in plants and mammals. Trends Genet. 23 (2007) 192-199
35. Ferrier D.E., and Minguillon C. Evolution of the Hox/ParaHox gene clusters. Int. J. Dev. Biol. 47 (2003) 605-611
36. Fontana W. Modelling evo-devo with RNA. Bioessays 24 (2002) 1164-1177
37. Forgács G., and Newman S.A. Biological Physics of the Developing Embryo (2005), Cambridge University Press, Cambridge
38. Genissel A., McIntyre L.M., Wayne M.L., and Nuzhdin S.V. Cis and trans regulatory effects contribute to natural variation in transcriptome of Drosophila melanogaster. Mol. Biol. Evol. 25 (2008) 101-110
39. Gerhart J., and Kirschner M. Cells, Embryos, and Evolution (1997), Blackwell Science, Malden
40. Ghildiyal M., and Zamore P.D. Small silencing RNAs: an expanding universe. Nat. Genet. 10 (2009) 94-108
41. Gibson G., and Dworkin I. Uncovering cryptic genetic variation. Nat. Rev. Genet. 5 (2004) 681-690
42. Gibson G., and Gehring W. Head and thoracic transformations caused by ectopic expression of Antennapedia during Drosophila development. Development 102 (1988) 657-675
43. Gilbert S.F. The reactive genome. In: Muller G., and Newman S.A. (Eds). The Origination of Organismal Form (2003), MIT Press, Cambridge, MA 87-101 Vienna Series in Theoretical Biology
44. Gómez-Skarmeta J.L., Rodríguez I., Martínez C., Culí J., Ferrés-Marcó D., Beamonte D., et al. Cis-regulation of achaete and scute: shared enhancer-like elements drive their coexpression in proneural clusters of the imaginal discs. Genes Dev. 9 (1995) 1869-1882
45. Grad Y.H., Roth F.P., Halfon M.S., and Church G.M. Prediction of similarly acting cis-regulatory modules by subsequence profiling and comparative genomics in Drosophila melanogaster and D. pseudoobscura. Bioinformatics 20 (2004) 2738-2750
46. Hahn M.W., and Wray G.A. The g-value paradox. Evol. Dev. 4 (2002) 73-75
47. Hamant O., Heisler M.G., Jönsson H., Krupinski P., Uyttewaal M., Bokov P., et al. Developmental patterning by mechanical signals in Arabidopsis. Science 322 (2008) 1650-1655
48. Hare E.E., Peterson B.K., Iyer V.N., Meier R., and Eisen M.B. Sepsid even-skipped enhancers are functionally conserved in Drosophila despite lack of sequence conservation. PLoS Genet. 4 (2008) e1000106
49. Held Jr. L.I. Imaginal Discs: The Genetic and Molecular Logic of Pattern Formation (2002), Cambridge University Press, Cambridge
50. Held Jr. L.I., Grimson M.J., and Du Z. Proving an old prediction: the sex comb rotates at 16 to 24 hours after pupariation. Drosoph. Inf. Serv. 87 (2004) 76-78
51. Hilgenfeldt S., Erisken S., and Carthew R.W. Physical modeling of cell geometric order in an epithelial tissue. Proc. Natl. Acad. Sci. USA 105 (2008) 907-911
52. Hinman V.F., Nguyen A.T., Cameron R.A., and Davidson E.H. Developmental gene regulatory network architecture across 500 million years of echinoderm evolution. Proc. Natl. Acad. Sci. USA 100 (2003) 13356-13361
53. Ikuta T., Yoshida N., Satoh N., and Saiga H. Ciona intestinalis Hox gene cluster: its dispersed structure and residual collinear expression in development. Proc. Natl. Acad. Sci. USA 101 (2004) 15118-15123
54. International Human Genome Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature 409 (2001) 860-921
55. International Human Genome Sequencing Consortium. Finishing the euchromatic sequence of the human genome. Nature 431 (2004) 931-945
56. Johannsen W. The genotype conception of heredity. Am. Nat. 45 (1911) 129-159
57. Kamath B.M., Thiel B.D., Gai X., Conlin L.K., Munoz P.S., Glessner J., et al. SNP array mapping of chromosome 20p deletions: genotypes, phenotypes, and copy number variation. Hum. Mutat. 30 (2008) 371-378
58. Katzman S., Kern A.D., Bejerano G., Fewell G., Fulton L., Wilson R.K., et al. Human genome ultraconserved elements are ultraselected. Science 317 (2007) 915
59. Kauffman S.A. The Origins of Order: Self-Organization and Selection in Evolution (1993), Oxford University Press, Oxford
60. Kmita M., and Duboule D. Organizing axes in time and space; 25 years of colinear tinkering. Science 301 (2003) 331-333
61. Kopp A., and True J.R. Evolution of male sexual characters in the Oriental Drosophila melanogaster species group. Evol. Dev. 4 (2002) 278-291
62. Kucharski R., Maleszka J., Foret S., and Maleszka R. Nutritional control of reproductive status in honeybees via DNA methylation. Science 319 (2008) 1827-1830
63. Lai E.C., Tomancak P., Williams R.W., and Rubin G.M. Computational identification of Drosophila microRNA genes. Genome Biol. 4 (2003) R42
64. Larsen E. Tissue strategies as developmental constraints: implications for animal evolution. Trends Ecol. Evol. 7 (1992) 414-417
65. Larsen E., and Atallah J. Epigenesis, preformation and the Humpty Dumpty problem. In: Hall B.K., and Hallgrimmsson B. (Eds). Epigenesis (2009), University of California Press, Berkeley
66. Larsen E., and McLaughlin H. The morphogenetic alphabet: lessons for simple-minded genes. Bioessays 7 (1987) 130-132
67. Larsen E., Lee T., and Glickman N. Antenna to leg transformation: dynamics of developmental competence. Dev. Genet. 19 (1996) 333-339
68. Lee R.C., Feinbaum R.L., and Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75 (1993) 843-854
69. Levine M., and Davidson E.H. Gene regulatory networks for development. Proc. Natl. Acad. Sci. USA 102 (2005) 4936-4942
70. Lewis E.B. A gene complex controlling segmentation in Drosophila. Nature 276 (1978) 565-570
71. Lim L.P., Lau N.C., Weinstein E.G., Abdelhakim A., Yekta S., Rhoades M.W., et al. The micro-RNAs of Caenorhabditis elegans. Genes Dev. 17 (2003) 991-1008
72. Ludwig M.Z., Patel N.H., and Kreitman M. Functional analysis of eve stripe 2 enhancer evolution in Drosophila: rules governing conservation and change. Development 125 (1998) 949-958
73. Ludwig M.Z., Bergman C., Patel N.H., and Kreitman M. Evidence for stabilizing selection in a eukaryotic enhancer element. Nature 403 (2000) 564-567
74. Lund A.M., Aström E., Söderhäll S., Schwartz M., and Skovby F. Osteogenesis imperfecta: mosaicism and refinement of the genotype-phenotype map in OI type III. Hum Mutat. 13 (1999) 503 Mutations in brief no. 242. Online
75. Mammoto A., Connor K.M., Mammoto T., Yung C.W., Huh D., Aderman C.M., et al. A mechanosensitive transcriptional mechanism that controls angiogenesis. Nature 457 (2009) 1103-1108
76. Marcellini S., and Simpson P. Two or four bristles: functional evolution of an enhancer of scute in Drosophilidae. PLoS Biol. 4 (2006) e386
77. Markstein M., Markstein P., Markstein V., and Levin M.S. Genome-wide analysis of clustered dorsal binding sites identifies putative target genes in the Drosophila embryo. Proc. Natl. Acad. Sci. USA 99 (2002) 546-548
78. Mathi S.K., and Larsen E. Patterns of cell division in imaginal discs of Drosophila. Tissue Cell 20 (1988) 461-472
79. Mayr E. Animal Species and Evolution (1963), Harvard University Press, Cambridge, MA
80. Mayr E. The Growth of Biological Thought (1982), Harvard University Press, Cambridge, MA
81. McDonald J.H., and Kreitman M. Adaptive protein evolution at the Adh locus in Drosophila. Nature 351 (1991) 114-116
82. McNellis T.W., and Deng X.W. Light control of seedling morphogenetic pattern. Plant Cell 7 (1995) 1749-1761
83. Medrano-Soto A., Pal D., and Eisenberg D. Inferring molecular function: contributions from functional linkages. Trends Genet. 24 (2008) 587-589
84. Medrano-Soto A., Pal D., and Eisenberg D. Inferring molecular function: contributions from functional linkages. Trends Genet. 12 (2008) 587-590
85. Moore D.S. The Dependent Gene: The Fallacy of 'Nature vs. Nurture (2003), Henry Holt and Company, New York
86. Morgan T.H. Experimental Zoology (1907), The Macmillan Company, New York
87. Morimoto R. Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes Dev. 12 (1998) 3788-3796
88. Moses A.M., Pollard D., Nix D.A., Iyer V.N., Li X.Y., Biggin M.D., et al. Large-scale turnover of functional transcription factor binding sites in Drosophila. PLoS Comput. Biol. 2 (2006) e130
89. Moses A.M., Hériché J., and Durbin R. Clustering of phosphorylation site recognition motifs can be exploited to predict the targets of cyclin-dependent kinase. Genome Biol. 8 (2007) R23
90. Moses A.M., Liku M.E., Li J.J., and Durbin R. Regulatory evolution in proteins by turnover and lineage-specific changes of cyclin-dependent kinase concensus sites. Proc. Natl. Acad. Sci. USA 104 (2007) 17713-17718
91. Moss E.G. Heterochronic genes and the nature of developmental time. Curr. Biol. 17 (2007) R425-R434
92. Muller G.B., and Streicher J. Ontogeny of the syndesmosis tibiofibularis and the evolution of the bird hindlimb: a caenogenetic feature. Anat. Embryol. (Berl.) 179 (1989) 327-339
93. Nelson C.E., Hersh B.M., and Carroll S.B. The regulatory content of intergenic DNA shapes genome architecture. Genome Biol. 5 (2004) R25
94. Nuzhdin S.V., Tufts D.M., and Hahn M.W. Abundant genetic variation in transcript level during early Drosophila development. Evol. Dev. 10 (2008) 683-689
95. Olivieri P., Tu Q., and Davidson E.H. Global regulatory logic for specification of an embryonic cell lineage. Proc. Natl. Acad. Sci. USA 105 (2008) 5955-5962
96. Patterson D., Rahmani Z., Donaldson D., Gardiner K., and Jones C. Physical mapping of chromosome 21. Prog. Clin. Biol. Res. 384 (1993) 33-50
97. Pennacchio L.A., Ahituv N., Moses A.M., Prabhakar S., Nobrega M.A., Shoukry M., et al. In vivo enhancer analysis of human conserved non-coding sequences. Nature 444 (2006) 499-502
98. Pontecorvo G. Untitled book review. Q. Rev. Biol. 26 (1951) 52-53
99. Probst A.V., Dunleavy E., and Almouzni G. Epigenetic inheritance during the cell cycle. Nat. Rev. Mol. Cell Biol. 10 (2009) 192-206
100. Rajewsky N. microRNA target predictions in animals. Nat. Genet. 38 (2006) 8-13
101. Randsholt N.B., and Santamaria P. How Drosophila change their combs: the Hox gene Sex combs reduced and sex comb variation among Sophophora species. Evol. Dev. 10 (2008) 121-133
102. Revilla-i-Domingo R., Oliveri P., and Davidson E.H. A missing link in the sea urchin embryo gene regulatory network: hsC and the double negative specification of micromeres. Proc. Natl. Acad. Sci. USA 104 (2007) 12383-12388
103. Ririe T.O., Fernandes J.S., and Sternberg P.W. The Caenorhabditis elegans vulva: a post-embryonic gene regulatory network controlling organogenesis. Proc. Natl. Acad. Sci. USA 105 (2008) 20095-20099
104. Rockman M.V. Reverse engineering the genotype-phenotype map with natural genetic variation. Nature 456 (2008) 738-744
105. Ronshaugen M., McGinnis N., and McGinnis W. Hox protein mutation and macroevolution of the insect body plan. Nature 415 (2002) 914-917
106. Ronshaugen M., Biemar F., Piel J., Levine M., and Lai E.C. The Drosophila microRNA iab-4 causes a dominant homeotic transformation of halteres to wings. Genes Dev. 19 (2005) 2947-2952
107. Rosner F. Medicine in the Bible and the Talmud (1995), KTAV Publishing House, Inc., Jersey City
108. Rosso L., Marques A.C., Weier M., Lambert N., Lambot M., Vanderhaeghen P., et al. Birth and rapid subcellular adaptation of a hominoid-specific CDC14 protein. PLoS Biol. 6 (2008) e140
109. Scanga S., Manoukian A., and Larsen E. Time- and concentration-dependent response of the Drosophila antenna imaginal disc to Antennapedia. Dev. Biol. 169 (1995) 673-682
110. Seo H.C., Edvardsen R.B., Maeland A.D., Bjordal M., Jensen M.F., Hansen A., et al. Hox cluster disintegration with persistent anteroposterior order of expression in Oikopleura dioica. Nature 431 (2004) 67-71
111. Shermoen A.W., and O'Farrell P.H. Progression of the cell cycle through mitosis leads to abortion of nascent transcripts. Cell 67 (1991) 303-310
112. Shi W., Levine M., and Davidson B. Unraveling genomic regulatory networks in the simple chordate, Ciona intestinalis. Genome Res. 15 (2009) 1668-1674
113. Shippy T.D., Ronshaugen M., Cande J., He J., Beeman R.W., Levine M., et al. Analysis of the Tribolium homeotic complex: insights into mechanisms constraining insect Hox clusters. Dev. Genes Evol. 218 (2008) 127-139
114. Siegal M.L., and Bergman A. Waddington's canalization revisited: developmental stability and evolution. Proc. Natl. Acad. Sci. USA 99 (2002) 10528-10532
115. Siepel A., Bejerano G., Pedersen J.S., Hinrichs A.S., Hou M., Rosenbloom K., et al. Evolutionarily conserved elements in vertebrate, insect, worm and yeast genomes. Genome Res. 15 (2006) 1034-1050
116. Siggia E. Computational methods for transcriptional regulation. Curr. Opin. Genet. Dev. 15 (2005) 214-221
117. Stark A., Brennecke J., Bushati N., Russell R.B., and Cohen S.M. Animal microRNAs confer robustness to gene expression and have a significant impact on 3′UTR evolution. Cell 123 (2005) 1133-1146
118. Stathopoulos A., Van Drenth M., Erives A., Markstein M., and Levine M. Whole-genome analysis of dorsal-ventral patterning in the Drosophila embryo. Cell 111 (2002) 687-701
119. Stern C. Genetic Mosaics and Other Essays (1968), Harvard University Press, Boston
120. Sturtevant A.H. Inheritance of direction of coilling in limnaea. Science 58 (1923) 269-270
121. Surkova S., et al. Characterization of the Drosophila segment determination morphome. Dev. Biol. 313 (2008) 844-862
122. Tamada M., Sheetz M.P., and Sawada Y. Activation of a signaling cascade by cytoskeleton stretch. Dev. Cell 7 (2004) 709-718
123. Tanaka K., Barmina O., and Kopp A. Distinct developmental mechanisms underlie the evolutionary diversification of Drosophila sex combs. Proc. Natl. Acad. Sci. USA 106 (2009) 4764-4769
124. Tokunaga C. Cell lineage and differentiation on the male foreleg of Drosophila melanogaster. Dev. Biol. 4 (1962) 489-516
125. Townes P., and Holtfreter J. Directed movements and selective adhesions of embryonic amphibian cells. J. Exp. Zool. 128 (1955) 53-120
126. Tümpel S., Cambronero F., Sims C., Krumlauf R., and Wiedemann L.M. A regulatory module embedded in the coding region of Hoxa2 controls expression in rhombomere 2. Proc. Natl. Acad. Sci. USA 105 (2008) 20077-20082
127. Usui K., Goldstone C., Gilbert J., and Simpson P. Redundant mechanisms mediate bristle patterning on the Drosophila thorax. Proc. Natl. Acad. Sci. USA 105 (2008) 20112-20117
128. Vogel V., and Sheetz M. Local force and geometry sensing regulate cell functions. Nat. Rev. Mol. Cell Biol. 7 (2006) 265-275
129. von Dassow G., and Odell G.M. Design and constraints of the Drosophila segment polarity module: robust spatial patterning emerges from intertwined cell state switches. J. Exp. Zool. (Mol. Dev. Evol.) 294 (2002) 179-215
130. von Dassow G., Meir E., Munro E.M., and Odell G.M. The segment polarity network is a robust developmental module. Nature 406 (2000) 188-192
131. Waddington C.H. Genetic assimilation. Advances in Genetics (1961) 257-293
132. Wagner R.P., and Mitchell H.K. Genetics and Metabolism (1964), Wiley, New York
133. Weiss K.M. Phenotype and genotype. In: Hall B.K., and Olson W.M. (Eds). Keywords and Concepts in Evolutionary Developmental Biology (2003), Harvard University Press, Cambridge, USA 279-288
134. Weiss K.M., and Terwilliger J.D. How many diseases does it take to map a gene with SNPs?. Nat. Genet. 26 (2000) 151-157
135. Wightman B., Ha I., and Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75 (1993) 855-862
136. Woolfe A., Goodson M., Goode D.K., Snell P., McEwen G.K., Vavouri T., et al. Highly conserved non-coding sequences are associated with vertebrate development. PLoS Biol. 3 (2005) e7
137. Yu X., Lin J., Zack D.J., Mendell J.T., and Qian J. Analysis of regulatory network topology reveals functionally distinct classes of microRNAs. Nucleic Acids Res. 36 (2008) 6494-6503
138. Zacharias H. Emil Heitz (1892-1965): chloroplasts, heterochromatin, and polytene chromosomes. Genetics 141 (1995) 7-14