DOCSLIB.ORG

Environmental Programming of Heritable Epigenetic Changes In

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Environmental Programming of Heritable Epigenetic Changes In Copyright 8 1995 by the Genetics Society of America Environmental Programming of Heritable Epigenetic Changes in Paramutant r-gene Expression Using Temperatureand Light at a Specific Stage of Early Development in Maize Seedlings Bernard C. Mikula Defiance College, Defiance, Ohio 43512 Manuscript received April 21, 1994 Accepted for publication May 12, 1995 ABSTRACT Different heritable expression-states wereprogrammed into R alleles fromR/R-lst heterozygotes under different temperature conditions applied during a developmental period in which flowering is induced. At maturity, R-allele expressions in test crosses of male gametes derivedfrom R/R-lst seedlings raised 15 days in 32" and continuous light conditions differed significantly from those of sib seedlings raisedfor 15 days in 22" and continuous light conditions and shifted to six 12-hr light-dark cycles, days 16-21. This experiment provides the first evidencein higher organisms that environmental conditions, applied at a specific stage of development cause a heritable change in a specific allele expression. My earlier evidence required a statistical analysis for demonstrating heritable change; I present photographic evidence of this environmental effect on four R alleles. ARAMUTATION (BRINK1956) provides a sensitive controlled before or during tassel differentiation. I re- P genetic system where heritable quantitative varia- ported in a previous paper (MIKULA1967) that when tion in the expression of a single gene can be followed R is exposed to a paramutagenic allele (R-st),the envi- from generation to generation. BRINK showed that ronmental conditions canpromote significant heritable when the R allele (dark kernel pigmentation) is made change inR-allele expression. R alleles from plantsthat heterozygous with its allele, R-st (stippled pigment pat- as seedlings were raisedat 21" and LL conditions (con- tern), the R allele produces significantly less pigment tinuous light) during the third and fourth week of seed- after removal from a heterozygote withR-st. The change ling development, whencompared in testcross progeny, in R-allele expression is heritable; furthermore, all R conditioned significantly less pigment in test crossesat alleles (100%) upon removal from this R/R-st heterozy- maturity than Ralleles of plants matured from seedlings gous combination are changed, and the change is di- grown at the same temperature in LD (12-hr lightdark rected at the R locus only. Later studies(MIKULA 1961; cycles) conditions for this same period. The identifica- MCWHIRTERand BRINK 1962; COOPER 1964; STYLESand tion of acritical developmental period leading to BRINK1966) showedthat if the R allelewas maintained changes in R expression suggested that experimental with R-st alleles for several generations, paramutation control of paramutation was possible. Three other ob of the R allele was additive. This additive effecton theR servations reinforced this inference: the level of para- allele was followed in male gametesfor five generations mutation could be correlated with the number of LD (STYLESand BRINK 1966). FEDOROFF (1989), while .kycles in the third week of seedling development; pre- studying the ontogenetic expression of the transposon liminary tests showed a polarity ofparamutant R allele Spm (SupP-essm-Mutatm),reported evidence that an in- expression in which early pollen samples from the up active Spm, by association over severalgenerations with per branches of single tassels showed more paramuta- an active Spm, can become progressively more active. tion than samples taken from lower branches of the The R alleles and cryptic Spm elements in maize repre- same tassel; and incremental changes in paramutant sent genetic systems whose phenotypes can be incre- R expression from generation to generation (MIKULA mentallyprogrammed by previousassociation with 1961) showedthat small changes inthe level ofparamu- other genetic elementsduring development (FEDOROFF tation couldbe detected and amplified fromgeneration and BANKS 1988). to generation. Paramutation (BRINKet aL 1968; DOONERet al. 1991) Further, it was found that tassel initiation in the was considered to be the result of changes accumulated W22 inbred could be delayed under continuous light in the R gene throughout somatic development. Coo conditions. It then became possible to askthe following PER (1964) and SASTRY et al. (1965) reported variation questions: how early in the life of the seedling could in paramutation from gametes sampledfrom different tassel determination take place; did temperature and tassel branches reflected a mosaicism developmentally light play a role; how many lightdark cycles were re- Genetics 140 1379-1387 (August, 1995) 1380 Mikula B. C. quired fortassel determination; could thelevel ofpara- Scoring procedures: A sample of 50 kernels from each test- mutation be correlatedwith programmed environmen- cross ear was scored by matching each kernel against a set of standard kernels ranging from 0 (colorless) to20 (completely tal conditions applied in early seedling development; pigmented). Pooled means and standard deviations for each could paramutation be inhibited or driven toward the environmental treatment are reported in Figure 6. completely colorless level; when during early develop- ment is the seedling most responsive to environmental RESULTS variables of temperature and light; and could the level of paramutation in four new R accessions be correlated Extensive preliminary testing showed no tassels were with environmental conditions administered to young initiated in inbred W22 under LL conditions. This seedlings? made it possible to determine the number of LD cycles essential for tassel initiation. Tassel initiation was deter- MATERIALS AND METHODS mined 1 week after LD treatments, however plants re- mained in the inhibitory LL conditions until six to eight Seed stocks: Environmental programming strategy for the first 3 weeks of seedling development was based on work with plants could be assayed for the presence of tassel pri- the Rand R-st alleles in inbred W22 background provided by mordia. The presence of tassel primordia was deter- JERRY KERMICLE, University of Wisconsin. The effect of the mined by dissecting away the leaves surrounding the environment on paramutant R-allele expression,first re- terminal meristem, under magnification. The presence ported in inbred W22 (MIKULA1967), required a statistical of an elongated terminal meristem and the presence analysis for its evaluation. In an effort to find more responsive R alleles, new R allele accessions that had not undergone a of branch primordia were observed when tassel initia- high degree of inbreeding and selection were screened for tion had taken place. Figure l shows that tassels could dark kernel pigment expression. The four newR-g alleles be induced with six LD cycles applied days 16-21 at from New Mexico and Arizona, 221, 229, Z1, 269, supplied 22" or a week earlier with only four LD cycles applied by Native Seeds/SEARCH, Tucson, AZ, are reported as GI, days 11- 15 at 26". The results in Figure 1, based on the G3, G4, and G5, respectively in this document. The new R-g accessions condition, in r/r/R endosperm, a uniformly dark presence or absence of tassel primordia in seedlings of pigmentation, comparable to that of the W22 R-r gene. All the W22 inbred foreach combination of environmental four R-g lines were crossed to a R-kt (light stipple with few conditions, provided a model system that made it possi- very fine spots) known to causeintermediate levels of paramu- ble to test whether paramutation could be influenced tation of the R allele. For convenience, the R-g genes will be by combinations of temperature and light variables ap referred to simply as R, eliminating the lower case designa- tion,-g, signifjmg lackof plant color. The R-kt allele, in W22 plied at a time seedlings were undergoing thetransition background, was supplied by the Maize Genetics Coop., Uni- from vegetative to floral phase of meristematic activity. versity of Illinois. The testcross ears of RR-lst heterozygotes of alleles Growth chamber conditions: Seeds from single ears of the G1, G3, G4, and G5, in Figure 2, A and B, show that a R/R-kt heterozygotes, representing the four different R al- difference in the amount of pigment for all four new leles, were germinated on white, moist facial tissue pads in stainless steel, glasscovered pans. Continuous light was sup R alleles can be observed in response to early environ- plied by 14 200-W VHO cool white fluorescent tubes supple- mental conditions. Seedlings raised in 31" LL condi- mented by 12 60-W incandescent bulbs. In 3 or 4 days, when tions for the first 3 weeks in the left column of both coleoptiles were largeenough to handle safely, seedlings were photographs show kernels with less pigment than those transplanted to soil conditions in plastic pots. Seedlings were raised in 22" LD conditions during the same period. started 50-60 cm distant from the light source and grew to- The paramutagenic allele, R-lst, present in half of the ward the light for the remaining 2- or %week periods they were held in the controlled environment conditions. Average kernels on each ear, has a phenotype too light to be light intensiq during this early stageof seedling development visible in the photographs; thus, it is possible to com- was 35 W/m . Dark conditions were obtained by placing the pare, visually, the environmental contribution to the seedlings into light-tight boxes. For eachenvironmental treat- paramutation of
Load more

Recommended publications
  • Paramutation Alters Regulatory Control of the Maize Pl Locus
    Copyright 2000 by the Genetics Society of America Paramutation Alters Regulatory Control of the Maize pl Locus Jay B. Hollick,*,1 Garth I. Patterson,*,2 Ingrid M. Asmundsson*,3 and Vicki L. Chandler² *Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403-1229 and ²Department of Plant Sciences, University of Arizona, Tucson, Arizona 85721 Manuscript received October 14, 1999 Accepted for publication December 10, 1999 ABSTRACT The maize purple plant (pl) locus encodes a transcription factor required for anthocyanin pigment synthesis in vegetative and ¯oral tissues. The strongly expressed Pl-Rhoades (Pl-Rh) allele is unstable, spontaneously changing to weaker expression states (PlЈ) at low frequencies and exclusively changing to PlЈ in PlЈ/Pl-Rh heterozygotes. The weakly expressed PlЈ state is mitotically and meiotically stable, yet reversible. This type of allele-dependent, heritable alteration of gene control is called paramutation. Expression studies herein demonstrate that visible differences in anthocyanin pigment levels mirror pl RNA abundance and that pl paramutation is associated with reduced transcription of the pl gene. This transcriptional alteration is accompanied by acquisition of light-dependent regulation. Restriction endonu- clease mapping indicates that these changes in pl gene regulation are not associated with detectable DNA alterations or with extensive changes in cytosine methylation patterns. Genetic tests show that Pl-Blotched (Pl-Bh), a structurally similar pl allele encoding an identical pl RNA and PL protein, does not participate in pl paramutation. This result suggests that if cis-acting sequences are required for pl paramutation they are distinct from the protein coding and immediately adjacent regions. A model is discussed in which pl paramutation results in heritable changes of chromatin structure that fundamentally alter regulatory interactions occurring during plant development.
    [Show full text]
  • Frequent Paramutation-Like Features of Natural Epialleles in Tomato
    bioRxiv preprint doi: https://doi.org/10.1101/177972; this version posted August 18, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Frequent paramutation-like features of natural epialleles in tomato Quentin Gouil1,2, and David C. Baulcombe1, 1Department of Plant Sciences, University of Cambridge, Cambridge, UK 2Walter and Eliza Hall Institute of Medical Research, Parkville, Australia Freakish and rare or the tip of the iceberg? Both phrases establishment and/or maintenance of the epigenetic mark. have been used to refer to paramutation, an epigenetic drive Our interest in paramutation follows from an earlier study that contravenes Mendel’s first law of segregation. Although of sRNA in tomato lines in which homozygous regions were its underlying mechanisms are beginning to unravel, its under- introgressed from Solanum pennellii into Solanum lycoper- standing relies only on a few examples that may involve trans- sicum (cv. M82) (14). The resulting introgression lines (ILs) genes or artificially generated epialleles. By using DNA methy- each carry many loci at which sRNAs are more abundant than lation of introgression lines as an indication of past paramu- tation, we reveal that the paramutation-like properties of the in either parent: they are transgressive (15). To explain these H06 locus in hybrids of Solanum lycopersicum and a range of findings we invoked epigenetic mechanisms because, in some tomato relatives and cultivars depend on the timing of sRNA instances, there was hypermethylation of the genomic DNA production and conform to an RNA-directed mechanism.
    [Show full text]
  • The Case for Transgenerational Epigenetic Inheritance in Humans
    Mamm Genome (2008) 19:394–397 DOI 10.1007/s00335-008-9124-y COMMENTARY SERIES: FUTURE CHALLENGES AND OPPORTUNITIES IN MAMMALIAN FUNCTIONAL GENOMICS The case for transgenerational epigenetic inheritance in humans Daniel K. Morgan Æ Emma Whitelaw Received: 26 March 2008 / Accepted: 28 May 2008 / Published online: 29 July 2008 Ó Springer Science+Business Media, LLC 2008 Abstract Work in the laboratory mouse has identified a modifications to the proteins that package DNA. These group of genes, called metastable epialleles, that are modifications affect the transcriptional activity of the informing us about the mechanisms by which the epige- underlying genes and, once established, are relatively sta- netic state is established in the embryo. At these alleles, ble through rounds of cell division. transcriptional activity is dependent on the epigenetic state Some genes, termed metastable epialleles, have been and this can vary from cell to cell in the one tissue type. identified in the mouse at which the establishment of the The decision to be active or inactive is probabilistic and epigenetic state is probabilistic and as a result they exhibit sensitive to environmental influences. Moreover, in some variegation, i.e., cells of the same type do not all express cases the epigenetic state at these alleles can survive across the gene. They also exhibit variable expressivity in the generations, termed transgenerational epigenetic inheri- context of isogenicity, i.e., mice of the same genotype tance. Together these findings raise the spectre of (inbred) do not all express the gene to the same extent. The Lamarckism and epigenetics is now being touted as an agouti viable yellow (Avy) allele and the axin-fused (AxinFu) explanation for some intergenerational effects in human allele are two examples (Rakyan et al.
    [Show full text]
  • Paramutation, an Allelic Interaction, Is Associated with a Stable and Heritable Reduction of Transcription of the Maize B Regulatory Gene
    Copyright 0 1993 by the Genetics Society of America Paramutation, an Allelic Interaction, Is Associated With a Stable and Heritable Reduction of Transcription of the Maize b Regulatory Gene Garth I. Patterson, Christopher J. Thorpe and Vicki L. Chandler Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403 Manuscript received May 10, 1993 Accepted for publicationJuly 17, 1993 ABSTRACT The b gene of maize encodes a transcriptional activatorof anthocyanin pigment biosynthetic genes. Certain b alleles undergo paramutation: a unidirectional, heritable alterationof one allele causedby the presence of another allele. B-I (intensely pigmented plant) is always changed to B’ (weakly pigmented plant) in the B’/B-Z heterozygote, such that all progeny receive the B‘ allele. The “new” B’, which was B-I in the previous generation, is weakly pigmented and fully capable of changing another B-Z allele intoB’. It was not previously knownwhether paramutationis associated with altered b expression, altered B protein function or both. Our results show that B’ acts in trans to suppress the transcription of B-I, with transcription remaining low in subsequent generations,even when the original B’ allele segregates away. The products of B-Z and B’ are equally capable of activating the transcription of their target genes, indicating they are functionally equivalent. Genomic restriction maps, DNA sequence and methylationof B’ and B-I were compared. Despite dramatic differencesin phenotype and transcription of B’ and B-I, no evidence for rearrangements, changesin sequence or changes in methylation was found. These results provide no support for models involving “dominant negative” proteins, gene conversionor transposable element interactions.We suggest that b paramu- tation involves a physical interaction between the alleles that suppresses transcription and promotesa change in chromatin structure that is heritable.
    [Show full text]
  • Paramutation: an Encounter Leaving a Lasting Impression
    Review TRENDS in Plant Science Vol.10 No.6 June 2005 Paramutation: an encounter leaving a lasting impression Maike Stam1 and Ortrun Mittelsten Scheid2 1Swammerdam Institute for Life Sciences, Universiteit van Amsterdam, Kruislaan 318, 1098 SM Amsterdam, The Netherlands 2Gregor Mendel Institute of Molecular Plant Biology, Austrian Academy of Sciences, and University of Natural Resources and Applied Life Science, Muthgasse 18, A-1190 Vienna, Austria Paramutation is the result of heritable changes in gene associated with changes in transposition frequency [5], expression that occur upon interaction between alleles. transposition mechanism [6] or recombination [7].In Whereas Mendelian rules, together with the concept of addition, the term paramutation was recently applied to genetic transmission via the DNA sequence, can account trans inactivations between non-allelic homologous for most inheritance in sexually propagating organisms, sequences [8–10] but, for simplicity, we here use the paramutation-like phenomena challenge the exclusive- term ‘alleles’ for the interacting loci. ness of Mendelian inheritance. Most paramutation-like Paramutation alleles come in pairs of one ‘paramutable’ phenomena have been observed in plants but there is allele and one ‘paramutagenic’ allele (Figure 1b). The increasing evidence for its occurrence in other organ- paramutagenic allele provokes the change and conveys its isms, including mammals. Our knowledge of the own expression state, whereas the paramutable allele underlying mechanisms, which might involve RNA undergoes the epigenetic change and becomes a para- silencing, physical pairing of homologous chromosomal mutated allele, in genetic nomenclature often marked regions or both, is still limited. Here, we discuss the with a prime symbol (for example, R-r0).
    [Show full text]
  • Paramutation: Just a Curiosity Or Fine Tuning of Gene Expression in the Next Generation?
    298 Current Genomics, 2011, 12, 298-306 Paramutation: Just a Curiosity or Fine Tuning of Gene Expression in the Next Generation? Roberto Pilu* Dipartimento di Produzione Vegetale, Università degli Studi di Milano, Via Celoria 2, 20133 Milano, Italy Abstract: Gene silencing is associated with heritable changes in gene expression which occur without changes in DNA sequence. In eukaryotes these phenomena are common and control important processes, such as development, imprinting, viral and transposon sequence silencing, as well as transgene silencing. Among the epigenetic events, paramutation occurs when a silenced allele (named paramutagenic) is able to silence another allele (paramutable) in trans and this change is heritable. The silenced paramutable allele acquires paramutagenic capacity in the next generations. In the 1950s, Alexander Brink described for the first time the phenomenon of paramutation, occurring in maize at the colored1 (r1) gene, a complex locus (encoding myc-homologous transcription factors) that regulates the anthocyanin biosynthetic pathway. Since then, paramutation and paramutation-like interactions have been discovered in other plants and animals, suggesting that they may underlie important mechanisms for gene expression. The molecular bases of these phenomena are unknown. However in some cases, the event of paramutation has been correlated with changes in DNA methylation, chromatin structure and recently several studies suggest that RNA could play a fundamental role. This last consideration is greatly supported by genetic screening for mutants inhibiting paramutation, which allowed the identification of genes involved in RNA-directed transcriptional silencing, although it is possible that proteins are also required for paramutation. The meaning of paramutation in the life cycle and in evolution remains to be determined even though we might conjecture that this phenomenon could be involved in a fast heritability of favourable epigenetic states across generations in a non- Mendelian way.
    [Show full text]
  • Transgenerational Epigenetics
    CHAPTER Paternal epigenetic inheritance 6 Rahia Mashoodh1, Frances A. Champagne2 Department of Zoology, University of Cambridge, Cambridge, United Kingdom1; Department of Psychology, University of Texas at Austin, Austin, TX, United States2 Chapter outline Introduction.........................................................................................................................................107 Paternal intergenerational and transgenerational effects........................................................................108 Nutritional effects ................................................................................................................ 108 Drugs and toxins .................................................................................................................. 108 Social environments ............................................................................................................. 109 Paternal age......................................................................................................................... 110 Mechanisms of paternal intergenerational and transgenerational effects.................................................111 Genetic modification............................................................................................................. 111 Epigenetic modifications ....................................................................................................... 113 DNA methylation .................................................................................................................
    [Show full text]
  • Genetically Modified Plants
    Acta Bot. Neerl. 46(1), March 1997, p. 3-24 REVIEW Genomic stability and stability of expression in genetically modified plants G.D.F. Maessen Department ofExperimental Botany, KU Nijmegen Toernooiveld, 6525 ED Nijmegen, The Netherlands CONTENTS Summary 3 Introduction 4 Genetic stability 5 Genome size 8 Site of integration 8 Stability of expression 11 Conclusions 17 Acknowledgements 18 References 18 SUMMARY This review provides a survey of those factors that might influence genetic stability of genetically modified organisms and somatic in In this several hybrids breeding programmes. respect aspects may be distinguished: (i) host genomic factors that might influence genetic stability, (ii) events related to the introduction of new DNA into the genome and their effect on genetic stability, (iii) stability of of introduced gene expression newly DNA, and (iv) stability of the modified view genome. In our a gene is defined as being stable if it inherits according to Mendelian laws. Obviously, this can be valid for nuclear Non-Mendelian inheritance be caused only genes. may by intrinsic genomic factors or be the result of skewed segregation during meiosis. Newly introduced DNA may be stably integrated into the genome, yet data on its site of integration is limited. The level of expression and, thus, the strength of the related trait, may Variation in vary. expression may depend on the construct, such as the additional promoter or sequences such as MAR elements or the coding sequence itself, the site of integration and the species used. Another, and undesired, phenomenon is the silencing of expression of introduced The described the genes.
    [Show full text]
  • Bridging the Transgenerational Gap with Epigenetic Memory
    TIGS-1027; No. of Pages 11 Review Featured Review Bridging the transgenerational gap with epigenetic memory 1,2 1,2,3 Jana P. Lim and Anne Brunet 1 Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA 2 Neurosciences Program, Stanford University School of Medicine, Stanford, CA 94305, USA 3 Glenn Laboratories for the Biology of Aging, Stanford, CA 94305, USA It is textbook knowledge that inheritance of traits is suggesting that this phenomenon is more widespread than governed by genetics, and that the epigenetic modifica- originally thought. In parallel, a growing body of work has tions an organism acquires are largely reset between revealed that exposure of parents to environmental stimuli generations. Recently, however, transgenerational epi- could affect the phenotype of several generations of des- genetic inheritance has emerged as a rapidly growing cendants, suggesting that changes in epigenetic modifica- field, providing evidence suggesting that some epige- tions induced by environmental stimuli might be passed on netic changes result in persistent phenotypes across to descendants via the gametes. Importantly, the field has generations. Here, we survey some of the most recent recently made significant progress in garnering mechanis- examples of transgenerational epigenetic inheritance tic insight into the processes underlying transgenerational in animals, ranging from Caenorhabditis elegans to epigenetic inheritance, by implicating specific chromatin humans, and describe approaches and limitations to modifications and noncoding RNA molecules. studying this phenomenon. We also review the current In this review, we survey the most recent examples of body of evidence implicating chromatin modifications epigenetic inheritance induced by genetic and environmen- and RNA molecules in mechanisms underlying this un- tal perturbations in animals (epigenetic inheritance in conventional mode of inheritance and discuss its evolu- plants has been reviewed elsewhere [14,15]).
    [Show full text]
  • RNA-Mediated Trans-Communication Can Establish Paramutation at the B1 Locus in Maize
    RNA-mediated trans-communication can establish paramutation at the b1 locus in maize Mario Arteaga-Vazqueza, Lyudmila Sidorenkoa, Fernando A. Rabanala,b, Roli Shrivistavac, Kan Nobutac, Pamela J. Greenc, Blake C. Meyersc, and Vicki L. Chandlera,1 aBIO5 Institute and Department of Plant Sciences, University of Arizona, Tucson, AZ 85721; bDepartamento de Biología Molecular de Plantas, Instituto de Biotecnología, Universidad Nacional Autónoma de México, 62210 Cuernavaca, Morelos, Mexico; and cDepartment of Plant and Soil Sciences and Delaware Biotechnology Institute, University of Delaware, Newark, DE 19711 Contributed by Vicki L. Chandler, June 6, 2010 (sent for review April 23, 2010) Paramutation is the epigenetic transfer of information between a subset of transposable elements (TEs), transgenes, and several alleles that leads to the heritable change of expression of one allele. non-TE genes (7, 13–18). Paramutation at the b1 locus in maize requires seven noncoding tan- The b1 gene is one of only two genes for which the sequences dem repeat (b1TR) sequences located ∼100 kb upstream of the tran- mediating paramutation have been defined (12, 19, 20). The key scription start site of b1, and mutations in several genes required for sequences required for b1 paramutation are seven b1TR units b1TR paramutation implicate an RNA-mediated mechanism. The mediator (each of the units is 853 bp in length) of noncoding DNA ∼ b1 of paramutation (mop1) gene, which encodes a protein closely re- located 100 kb upstream of the transcription start site (20, 21). This sequence is unique to this location within the maize lated to RNA-dependent RNA polymerases, is absolutely required for B-I B′ paramutation.
    [Show full text]
  • Normal Botany
    Normal Botany David Baulcombe (2009) I wrote this short text for the Annual Record of Trinity College, Cambridge. An introduction to beachcombing Having reached a certain age I can now look back and reflect on the different approaches to scientific discovery. I see that very few people are visionaries who can both identify the big questions at the frontiers of knowledge and, just as important, see how to find an answer. The rest of us – practitioners of Thomas Kuhn’s “normal science” - are beachcombers. Like Newton we are as “a boy (or girl) playing on the seashore, and diverting myself in now and then finding a smoother pebble or a prettier shell than ordinary”. Newton of course was aware of the nearby “great ocean of truth” but the rest of us only see it if we pick up the smoother pebble, if ever. My life as a beachcomber started when I decided to do a PhD. My tutor at Leeds University advised that I should focus on what I thought is the most important question in biology and that, for me, involved genetic regulation. It would hold the key to many of the mysteries of biology and help meet challenges in healthcare and agriculture. Genetic regulation is best understood in terms of development: the sequence of events in which a single egg cell differentiates into a multicellular adult. Each of the cells in the adult has the same genes as the egg but different proteins. Crick’s central dogma of molecular biology tells us that ‘DNA makes RNA makes protein’ when a gene is switched on and so there must be an off switch if protein is not being made.
    [Show full text]
  • Paramutation and Gene Silencing in Plants Rob Martienssen
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE 810 Dispatch provided by Elsevier - Publisher Connector Epigenetic phenomena: Paramutation and gene silencing in plants Rob Martienssen Four cases of paramutation and gene silencing in transposable element (I-R), but neither this gene alone nor plants differ in their genetic properties, but each may the I-R transposon is responsible for the paramutation [4]. involve epigenetic interactions between transposable Instead, it is the other three r genes — or the duplicated elements. sequences that lie between them — that confer paramuta- genicity on this complex locus [4,5]. These three genes, Address: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. Nc1–3, are expressed at a very low level, resulting in a near-colorless (Nc) phenotype. Derivative alleles, gener- Current Biology 1996, Vol 6 No 7:810–813 ated by unequal crossing-over, have fewer repeats, are less paramutagenic and confer higher levels of seed pigmenta- © Current Biology Ltd ISSN 0960-9822 tion [4]. The upstream regions of the component r genes are extensively methylated in the most paramutagenic Gene silencing is a widespread phenomenon in plants, derivatives [5]. and can affect endogenous genes as well as transgenes integrated into the genome [1,2]. Gene silencing can be The paramutable R-r allele has three functional r genes induced by interactions between related genes, and one of [6]. One is expressed in plant (as opposed to seed) tissues, the best-known examples is named paramutation. Para- and is separated from the others by more than 190 kilo- mutation is the directed heritable alteration of one allele bases; it is not thought to play a major role in paramutation.
    [Show full text]