Abstract
The concept of clone is analysed with the aim of exploring the limits to which a phenotype can be said to be determined geneticaly. First of all, mutations that result from the replication, topological manipulation or lesion of DNA introduce a source of heritable variation in an otherwise identical genetic background. But more important, stochastic effects in many biological processes may superimpose a phenotypic variation which is not encoded in the genome. The source of stochasticity ranges from the random selection of alleles or whole chromosomes to be expressed in small cell populations, to fluctuations in processes such as gene expression, due to limiting amounts of the players involved. The picture emerging is that the term clone is a statistical over-simplification representing a series of individuals having essentially the same genome but capable of exhibiting wide phenotypic variation. Finally, to what extent fluctuations in biological processes, usually thought of as noise, are in fact signal is also discussed.
Similar content being viewed by others
Abbreviations
- GFP:
-
Green fluorescent protein
- lac:
-
lactose
- PEV:
-
position effect varigation
- TF:
-
transcription factor
- w +:
-
while +
References
Abkowitz J L, Taboada M, Shelton G H, Catlin S N, Guttorp P and Kiklevich J V 1998 An X chromosome gene regulates hematopoietic stem cell kinetics;Proc. Natl. Acad. Sci. USA 95 3862–3866
Ayoub N, Goldshmidt I and Cohen A 1999 Position effect variegation at the mating-type locus of fission yeast: a cisacting element inhibits covariegated expression of genes in the silent and expressed domains;Genetics 152 495–508
Becskei A, Seraphin B and Serrano L 2001 Positive feedback in eukaryotic gene networks: cell differentiation by graded to binary response conversion;EMBO J. 20 2528–2535
Biggar S R and Crabtree G R 2001 Cell signaling can direct either binary or graded transcriptional responses;EMBO J. 20 3167–3176
Blake W J, Ka M, Cantor C R and Collins J J 2003 Noise in eukaryotic gene expression;Nature (London) 422 633–637
Blattner F R, Plunkett G 3rd, Bloch C A, Perna N T, Burland V, Riley M, Collado-Vides J, Glasner J D, Rode C K, Mayhew G F, Gregor J, Davis N W, Kirkpatrick H A, Goeden M A, Rose D J, Mau B and Shao Y 1997 The complete genome sequence ofEscherichia coli K-12;Science 277 1453–1474
Boulanger P A, Yoshinaga S K and Berk A J 1987 DNA-binding properties and characterization of human transcription factor TFIIIC2;J. Biol. Chem. 262 15098–15105
Brown S W and Chandra H S 1973 Inactivation system of the mammalian X chromosome;Proc. Natl. Acad. Sci. USA 70 195–199
Bustabad S, Gonzalez T and Trujillo E 1997 Systemic lupus erythematosus in childhood. Concordance in a pair of monozygotic twins for anti-dsDNA antibodies and discordance for disease expression;J. Rheumatol. 24 1450–1451
Chargaff E 2000 Molecular slavery;J. Biosci. 25 7–8
Cook D L, Gerber A N and Tapscott S J 1998 Modeling stochastic gene expression: implications for haploinsufficiency;Proc. Natl. Acad. Sci. USA 95 15641–15646
Corballis M C 1991The lopsided ape (Oxford: Oxford University Press), p. 97
Davey H M and Kell D B 1996 Flow cytometry and cell sorting of heterogeneous microbial populations: the importance of single-cell analyses;Microbiol. Rev. 60 641–696
Dingemanse M A, de Boer P A, Moorman A F, Charles R and Lamers W H 1994 The expression of liver-specific genes within rat embryonic hepatocytes is a discontinuous process;Differentiation 56 153–162
Elowitz M B, Levine A J, Siggia E D and Swain P S 2002 Stochastic gene expression in a single cell;Science 297 1183–1186
Ehrlich J, Sankoff D and Nadeau J H 1997 Synteny conservation and chromosome rearrangements during mammalian evolution;Genetics 147 289–296
Fiering S, Whitelaw E and Martin D I 2000 To be or not to be active: the stochastic nature of enhancer action;Bioessays 22 381–387
Francastel C, Walters M C, Groudine M and Martin D I 1999 A functional enhancer suppresses silencing of a transgene and prevents its localization close to centrometric heterochromatin;Cell 99 259–269
Gardner T S, Cantor C R and Collins J J 2000 Construction of a genetic toggle switch inEscherichia coli.Nature (London) 403 339–342
Gregersen P K 1993 Discordance for autoimmunity in monozygotic twins. Are “identical” twins really identical?;Arthritis Rheum. 36 1185–1192
Grunstein M 1998 Yeast Heterochromatin: Regulation of Its Assembly and Inheritance by Histones;Cell 93 325–328
Gurdon J B, Kato K and Lemaire P 1993 The community effect, dorsalization and mesoderm induction;Curr. Opin. Genet. Dev. 3 662–667
Gu Z, Steinmetz L M, Gu X, Scharfe C, Davis R W and Li W H 2003 Role of duplicate genes in genetic robustness against null mutations;Nature (London) 421 63–66
Kato H, Nagamine M, Kominami R and Muramatsu M 1986 Formation of the transcription initiation complex on mammalian rDNA;Mol. Cell. Biol. 6 3418–3427
Kellner J R and Alford R A 2003 The ontogeny of fluctuating asymmetry;Am. Nat. 161 931–947
Klingenberg C P 2003 A developmental perspective on developmental instability theory, models and mechanisms; inDevelopmental instability causes and consequences (ed.) M Polak (New York: Oxford University Press) pp 14–34
Kruglyak L and Nickerson D A 2001 Variation is the spice of life;Nat. Genet. 27 234–236
Lewis J, Slack J M W and Wolpert L 1977 Thresholds in development;J. Theor. Biol. 65 579–590
Liyanage M, Coleman A, du Manoir S, Veldman T, McCormack S, Dickson R B, Barlow C, Wynshaw-Boris A, Janz S, Wienberg J, Ferguson-Smith MA, Schrock E and Ried T 1996 Multicolour spectral karyotyping of mouse chromosomes;Nat. Genet. 14 312–315
Lyon M F 1962 Sex chromatin and gene action in the mammalian X-chromosome;Am. J. Hum. Genet. 14 135–148
Machin G A 1996 Some causes of genotypic and phenotypic discordance in monozygotic twin pairs;Am. J. Med. Genet. 61 216–228
McAdams H H and Arkin A 1997 Stochastic mechanisms in gene expression;Proc. Natl. Acad. Sci. USA 94 814–819
Muller H J 1930 Types of visible variations induced by X-rays inDrosophila;J. Genet. 22 299–334
Murray J D 1989Mathematical biology (New York: Springer-Verlag)
Novick A and WeinerM 1957 Enzyme induction as an all-or-none phenomenon;Proc. Natl. Acad. Sci. USA 43 553–566
Newlands S, Levitt L K, Robinson C S, Karpf A B, Hodgson V R, Wade R P and Hardeman E C 1998 Transcription occurs in pulses in muscle fibers;Genes Dev. 12 2748–2758
Nijhout H F 2005 Stochastic Gene expression: Dominance, thresholds, and boundaries; inThe biology of genetic dominance Veitia R (ed.) (Georgetown: Landes Biosciences) (in press)
Nutt S L and Busslinger M 1999 Monoallelic expression of Pax5: a paradigm for the haploinsufficiency of mammalian Pax genes;Biol. Chem. 380 601–611
Ogawa Y, Lee J T and Xite 2003 X-inactivation intergenic transcription elements that regulate the probability of choice;Mol. Cell. 11 731–733
Osborne C S, Chakalova L, Brown K E, Carter D, Horton A, Debrand E, Goyenechea B, Mitchell J A, Lopes S, Reik W and Fraser P 2004 Active genes dynamically colocalize to shared sites of ongoing transcription;Nat. Genet. 36 1065–1071
Ozbudak E M, Thattai M, Kurtser I, Grossman A D and van Oudenaarden A 2002 Regulation of noise in the expression of a single gene;Nat. Genet. 31 69–73
Queitsch C, Sangster T A and Lindquist S 2002 Hsp90 as a capacitor of phenotypic variation;Nature (London) 417 618–624
Rutherford S L and Lindquist S 1998 Hsp90 as a capacitor for morphological evolution;Nature (London) 396 336–342
Schweidler E V 1906 Uber schwankungen der radioaktiven umwandlung;Comptes Rendus du Premièr Congrès International pour L’étude de la Radiologie et de l’Ionisation, Liège, Sep. 12–14, 1905. H Dunod and E Pinat, Paris, Section de physique
Shang Y, Hu X, DiRenzo J, Lazar M A and Brown M 2000 Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription;Cell 103 843–852
Siegele D A and Hu J C 1997 Gene expression from plasmids containing thearaBAD promoter at subsaturating inducer concentrations represents mixed populations;Proc. Natl. Acad. Sci. USA 94 8168–8172
Sutherland H G, Martin D I and Whitelaw E 1997 A globin enhancer acts by increasing the proportion of erythrocytes expressing a linked transgene;Mol. Cell. Biol. 17 1607–1614
Tiberio G 1994 M Z female twins discordant for X-linked diseases: a review;Acta. Genet. Med. Gemellol (Roma) 43 207–214
Veitia R A 2003 A sigmoidal transcriptional response: cooperativity, synergy and dosage effects;Biol. Rev. Camb. Philos. Soc. 78 149–170
Waddington C H 1942 Canalization of development and the inheritance of acquired characters;Nature (London) 150 563–565
Wakimoto B T 1998 Beyond the nucleosome: epigenetic aspects of position-effect variegation inDrosophila;Cell 93 321–324
Weinstein L S 2001 The role of tissue-specific imprinting as a source of phenotypic heterogeneity in human disease;Biol. Psychiatry 50 927–931
Wijgerde M, Grosveld F and Fraser P 1995 Transcription complex stability and chromatin dynamics in vivo;Nature (London) 377 209–213
Willard H F 1996 X chromosome inactivation, XIST, and pursuit of the X-inactivation center;cell 86 5–7
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Veitia, R.A. Stochasticity or the fatal ‘imperfection’ of cloning. J Biosci 30, 21–30 (2005). https://doi.org/10.1007/BF02705147
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF02705147