Genes, Development, and Cancer
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Uniting Micro- with Macroevolution Into an Extended Synthesis: Reintegrating Life’S Natural History Into Evolution Studies
Uniting Micro- with Macroevolution into an Extended Synthesis: Reintegrating Life’s Natural History into Evolution Studies Nathalie Gontier Abstract The Modern Synthesis explains the evolution of life at a mesolevel by identifying phenotype–environmental interactions as the locus of evolution and by identifying natural selection as the means by which evolution occurs. Both micro- and macroevolutionary schools of thought are post-synthetic attempts to evolution- ize phenomena above and below organisms that have traditionally been conceived as non-living. Microevolutionary thought associates with the study of how genetic selection explains higher-order phenomena such as speciation and extinction, while macroevolutionary research fields understand species and higher taxa as biological individuals and they attribute evolutionary causation to biotic and abiotic factors that transcend genetic selection. The microreductionist and macroholistic research schools are characterized as two distinct epistemic cultures where the former favor mechanical explanations, while the latter favor historical explanations of the evolu- tionary process by identifying recurring patterns and trends in the evolution of life. I demonstrate that both cultures endorse radically different notions on time and explain how both perspectives can be unified by endorsing epistemic pluralism. Keywords Microevolution · Macroevolution · Origin of life · Evolutionary biology · Sociocultural evolution · Natural history · Organicism · Biorealities · Units, levels and mechanisms of evolution · Major transitions · Hierarchy theory But how … shall we describe a process which nobody has seen performed, and of which no written history gives any account? This is only to be investigated, first, in examining the nature of those solid bodies, the history of which we want to know; and 2dly, in exam- ining the natural operations of the globe, in order to see if there now actually exist such operations, as, from the nature of the solid bodies, appear to have been necessary to their formation. -
Transvection in 2012: Site-Specific Transgenes Reveal a Plethora of Trans-Regulatory Effects
COMMENTARY Transvection in 2012: Site-Specific Transgenes Reveal a Plethora of Trans-Regulatory Effects Judith A. Kassis1 Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 In this commentary, Judith Kassis discusses Bateman et al., widespread in the Drosophila genome (Bateman et al. 2012; “Comparing Enhancer Action in cis and in trans” and Mellert Mellert and Truman 2012). and Truman “Transvection is Common Throughout the Dro- Both groups of researchers used the phi-C31 system to in- sophila Genome”, which are published in this issue of GENETICS. tegrate transgenes into specific genomic locations to look at the ability of one transgene to activate the expression of another, N Drosophila, homologous chromosomes are paired in so- greatly increasing our knowledge of trans-interactions and sug- Imatic cells (reviewed in McKee 2004), leading to the oppor- gesting many experiments for the future. However, beyond that, tunity for regulatory DNA on one chromosome to influence their approaches to studying transvection and the questions they the expression of a promoter located on the homologous addressed differ. Bateman et al. (2012) used recombination- chromosome (reviewed in Duncan 2002; Kennison and mediated cassette exchange (Bateman et al. 2006) to insert Southworth 2002). Such trans-regulatory interactions were a simple, defined enhancer, the GMR (which consists of five first reported by Ed Lewis (Lewis 1954) who found that binding sites for the eye transcriptional activator Glass) and allelic complementation between particular mutations within adefined promoter driving the expression of either GFP or the bithorax complex did not occur when the pairing of ho- mCherry into three different chromosomal insertion sites to ad- mologous chromosomes was disrupted. -
Hermann J. Muller's 1936 Letter to Stalin
The Mankind Quarterly 43 (3), Spring 2003, pp. 305-319 Hermann J. Muller’s 1936 Letter to Stalin John Glad1 University of Maryland This is the full text of a 1936 letter sent by the American geneticist H.J. Muller to Joseph Stalin advocating the creation of a eugenic program in the USSR. It was rejected by Stalin in favor of Lysenkoism. Key words: eugenics, communism, Lysenkoist theory, liberal roots of eugenics movement, Jewish scholars, Hermann J. Muller, Joseph Stalin, Stalinist, purges. Hermann Joseph Muller (1890-1967) received the Nobel Prize in 1946 for his work on the genetics of drosophila, whose brief generational life made it an ideal laboratory in miniature. Within a decade, however, following the discovery in 1953 of the double helical structure of DNA, drosophila studies began to be regarded as classical genetics and gave way to microbial and molecular genetics devoted to gene structure and function. Muller looked upon his drosophila research as science to be applied to the genetic betterment of the human species. A popular misconception with regard to eugenics is that it was exclusively a product of political conservatism. In point of fact the movement had its roots in the left as much as in the right. Muller himself was a devoted communist and an idealistic believer in human rights. Bearing in mind that Jewish scholars played a significant role in the eugenics movement, it should not come as a surprise to find that Muller was Jewish on his mother’s side. Indeed, he wrote a letter to Stalin on the subject of eugenics at the suggestion of the Russian-Jewish physician Solomon Levit, whose main interests lay in the field of genetics, especially in twin studies. -
Perspectives
Copyright Ó 2007 by the Genetics Society of America Perspectives Anecdotal, Historical and Critical Commentaries on Genetics Edited by James F. Crow and William F. Dove Guido Pontecorvo (‘‘Ponte’’): A Centenary Memoir Bernard L. Cohen1 *Institute of Biomedical and Life Sciences, Division of Molecular Genetics, University of Glasgow, Glasgow G11 6NU, Scotland N a memoir published soon after Guido Pontecor- mendation, Pontecorvo applied for and was awarded a I vo’s death (Cohen 2000), I outlined his attractive, small, short-term SPSL scholarship. Thus, he could again but sometimes irascible, character, his history as a apply a genetical approach to a problem related to refugee from Fascism, and his most significant contribu- animal breeding (Pontecorvo 1940a), the branch of tions to genetics. The centenary of his birth (November agriculture in which he had most recently specialized 29, 1907) provides an opportunity for further reflec- with a series of data-rich articles (e.g.,Pontecorvo 1937). tions—personal, historical, and genetical.2 But Ponte was stranded in Edinburgh by the outbreak of Two points of interest arise from the support that war and the cancellation of a Peruvian contract and Ponte received from the Society for the Protection of continued for about 2 years to be supported by SPSL. Science and Learning (SPSL). Formed in 1933 as the The first point of interest is a prime example of the Academic Assistance Council, SPSL aimed to assist the power of chance and opportunity. Renting a small room refugees who had started to arrive in Britain from the in the IAG guest house, Ponte there met Hermann European continent (among them Max Born, Ernst Joseph Muller, who had recently arrived from Russia. -
Multi-Scale Organization of the Drosophila Melanogaster Genome
G C A T T A C G G C A T genes Review Multi-Scale Organization of the Drosophila melanogaster Genome Samantha C. Peterson † , Kaylah B. Samuelson † and Stacey L. Hanlon * Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, USA; [email protected] (S.C.P.); [email protected] (K.B.S.) * Correspondence: [email protected] † These authors contributed equally to this work. Abstract: Interphase chromatin, despite its appearance, is a highly organized framework of loops and bends. Chromosomes are folded into topologically associating domains, or TADs, and each chromosome and its homolog occupy a distinct territory within the nucleus. In Drosophila, genome organization is exceptional because homologous chromosome pairing is in both germline and somatic tissues, which promote interhomolog interactions such as transvection that can affect gene expression in trans. In this review, we focus on what is known about genome organization in Drosophila and discuss it from TADs to territory. We start by examining intrachromosomal organization at the sub-chromosome level into TADs, followed by a comprehensive analysis of the known proteins that play a key role in TAD formation and boundary establishment. We then zoom out to examine interhomolog interactions such as pairing and transvection that are abundant in Drosophila but rare in other model systems. Finally, we discuss chromosome territories that form within the nucleus, resulting in a complete picture of the multi-scale organization of the Drosophila genome. Keywords: Drosophila; topologically associating domain; insulator; pairing; transvection; B chromo- some; cytogenetics Citation: Peterson, S.C.; Samuelson, K.B.; Hanlon, S.L. -
September: Forskarnas Älsklingsdjur
Forskarnas älsklingsdjur Slå inte ihjäl den irriterande bananflugan nästa gång den lilla, 2-3 mm långa bumlingen surrar runt i köket. Den är ett under- verk när det gäller iakttagelseförmåga och flygprecision. Förundras i Karl von Frisch Konrad Lorenz Nikolaas Tinbergen stället över denna lilla fluga som lärt forskarna så mycket! Nobelpriset i fysiologi eller medicin 1973 tilldelades gemensamt Bananflugan Drosophila( melanogaster) är en favorit för forskare. Karl von Frisch, Konrad Lorenz och Nikolaas Tinbergen ”för deras Redan i början av 1900-talet började man studera bananflugor upptäckter rörande organisation och utlösning av individuella eftersom de är lätta att odla och förökar sig snabbt med en ge- och sociala beteendemönster”. Frisch och Tinbergen studerade insekter, dock inte bananflugor. Läs mer på www.nobelprize.org nerationstid på endast cirka två veckor. Många genetiska varian- Bananfluga (Wikimedia Commons) ter med exempelvis olika ögon- och kroppsfärg har bildats på na- turlig väg eller framkallats med röntgenstålning eller kemikalier. Nobelpristagare som arbetat med bananflugor (se www.nobel- prize.org, Education): Beteendestudier med bananflugor • Thomas Hunt Morgan (1933) beskrev kromosomernas be- Vilda bananflugor massförökas ofta inomhus tydelse för hur egenskaper ärvs. på sensommaren om övermogen frukt får ligga • Hermann Joseph Muller (1946) upptäckte att röntgenstrål- framme. Fånga in dem i en burk med en tuss ning ger mutationer. bomull indränkt med vinäger. Se även www. • Edward B. Lewis, Christiane Nüsslein-Volhard och Eric F. bioresurs.uu.se (Inköp/Levande organismer) för Wieschaus (1995) studerade embryonalutveckling. adresser till företag som säljer bananflugor. Odlingsrör med bananflugor och parande bananflugor Klassiska skollaborationer är korsningsförsök med bananflugor Bygg en testkammare av två stora petflaskor. -
And Abdominal-B in Drosqbhilu Melanogaster
Copyright 0 1995 by the Genetics Society of America and Trans Interactions Between the iab Regulatory Regions and abdominal-A and Abdominal-B in Drosqbhilu melanogaster Jd Eileen Hendrickson and Shigeru Sakonju Department of Human Genetics, Howard Hughes Medical Institute, University of Utah, Salt Lake City, Utah 841 12 Manuscript received August 15, 1994 Accepted for publication November 8, 1994 ABSTRACT The infra-abdominal ( iab) elements in the bithorax complex of Drosophila melanogaster regulate the transcription of the homeotic genesabdominal-A ( abd-A) and Abdominal-B ( Abd-B) in cis. Here we describe two unusual aspects of regulation by the iab elements, revealed by an analysis of an unexpected comple- mentation between mutations in the Abd-B transcription unit and these regulatory regions. First,we find that iab-6 and iab7 can regulate Abd-B in trans. This iab trans regulation is insensitive to chromosomal rearrangements that disrupt transvection effects at the nearby Ubx locus. In addition, we show that a transposed Abd-B transcription unitand promoter on the Ychromosomecan be activatedby iabelements located on the third chromosome. These results suggest that the iab regions can regulate their target promoter located ata distant sitein the genomein a manner that is much less dependent on homologue pairing than other transvection effects.The iab regulatory regionsmay have a very strong affinity for the target promoter, allowing them to interactwith each other despite the inhibitory effectsof chromosomal rearrangements. Second, by generating abd-A mutations on rearrangement chromosomes that break in the iab-7 region, we show that these breaks induce theiab elements to switch their target promoter from Abd-B to abd-A. -
Timeline of Genomics (1901–1950)*
Research Resource Timeline of Genomics (1901{1950)* Year Event and Theoretical Implication/Extension Reference 1901 Hugo de Vries adopts the term MUTATION to de Vries, H. 1901. Die Mutationstheorie. describe sudden, spontaneous, drastic alterations in Veit, Leipzig, Germany. the hereditary material of Oenothera. Thomas Harrison Montgomery studies sper- 1. Montgomery, T.H. 1898. The spermato- matogenesis in various species of Hemiptera and ¯nds genesis in Pentatoma up to the formation that maternal chromosomes only pair with paternal of the spermatid. Zool. Jahrb. 12: 1-88. chromosomes during meiosis. 2. Montgomery, T.H. 1901. A study of the chromosomes of the germ cells of the Metazoa. Trans. Am. Phil. Soc. 20: 154-236. Clarence Ervin McClung postulates that the so- McClung, C.E. 1901. Notes on the acces- called accessory chromosome (now known as the \X" sory chromosome. Anat. Anz. 20: 220- chromosome) is male determining. 226. Hermann Emil Fischer(1902 Nobel Prize Laure- 1. Fischer, E. and Fourneau, E. 1901. UberÄ ate for Chemistry) and Ernest Fourneau report einige Derivate des Glykocolls. Ber. the synthesis of the ¯rst dipeptide, glycylglycine. In Dtsch. Chem. Ges. 34: 2868-2877. 1902 Fischer introduces the term PEPTIDES. 2. Fischer, E. 1907. Syntheses of polypep- tides. XVII. Ber. Dtsch. Chem. Ges. 40: 1754-1767. 1902 Theodor Boveri and Walter Stanborough Sut- 1. Boveri, T. 1902. UberÄ mehrpolige Mi- ton found the chromosome theory of heredity inde- tosen als Mittel zur Analyse des Zellkerns. pendently. Verh. Phys -med. Ges. WÄurzberg NF 35: 67-90. 2. Boveri, T. 1903. UberÄ die Konstitution der chromatischen Kernsubstanz. Verh. Zool. -
Interallelic Transcriptional Enhancement As an in Vivo Measure of Transvection in Drosophila Melanogaster
INVESTIGATION Interallelic Transcriptional Enhancement as an in Vivo Measure of Transvection in Drosophila melanogaster Geoffrey P. Noble,*,† Patrick J. Dolph,‡ and Surachai Supattapone*,†,1 *Department of Biochemistry and Cell Biology and †Department of Medicine, Geisel School of Medicine, and ‡Department of Biology, Dartmouth College, Hanover, New Hampshire 03755 ABSTRACT Transvection—pairing-dependent interallelic regulation resulting from enhancer action in KEYWORDS trans—occurs throughout the Drosophila melanogaster genome, likely as a result of the extensive somatic transvection homolog pairing seen in Dipteran species. Recent studies of transvection in Drosophila have demonstrated enhancer important qualitative differences between enhancer action in cis vs. in trans, as well as a modest synergistic somatic pairing effect of cis- and trans-acting enhancers on total tissue transcript levels at a given locus. In the present study, GAL4-UAS we identify a system in which cis- and trans-acting GAL4-UAS enhancer synergism has an unexpectedly large quantitative influence on gene expression, boosting total tissue transcript levels at least fourfold relative to those seen in the absence of transvection. We exploit this strong quantitative effect by using publicly available UAS-shRNA constructs from the TRiP library to assay candidate genes for transvection activity in vivo. The results of the present study, which demonstrate that in trans activation by simple UAS enhancers can have large quantitative effects on gene expression in Drosophila, have important new implications for experimental design utilizing the GAL4-UAS system. The nuclear genome is often pictured to function as a linear arrange- which there is widespread physical interaction between maternal and ment of nucleotides grouped into genes and regulatory elements paternal homologous chromosomes (McKee 2004; Metz 1916; Stevens operating more or less locally in cis . -
Transvection Is Common Throughout the Drosophila Genome
INVESTIGATION Transvection Is Common Throughout the Drosophila Genome David J. Mellert1 and James W. Truman Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147 ABSTRACT Higher-order genome organization plays an important role in transcriptional regulation. In Drosophila, somatic pairing of homologous chromosomes can lead to transvection, by which the regulatory region of a gene can influence transcription in trans.We observe transvection between transgenes inserted at commonly used phiC31 integration sites in the Drosophila genome. When two transgenes that carry endogenous regulatory elements driving the expression of either LexA or GAL4 are inserted at the same integration site and paired, the enhancer of one transgene can drive or repress expression of the paired transgene. These transvection effects depend on compatibility between regulatory elements and are often restricted to a subset of cell types within a given expression pattern. We further show that activated UAS transgenes can also drive transcription in trans. We discuss the implication of these findings for (1) understanding the molecular mechanisms that underlie transvection and (2) the design of experiments that utilize site- specific integration. HOUGH much of transcriptional regulation is due to hypomorphic or loss-of-function alleles of a gene exhibit Tregulatory elements that act in cis, relatively near the pairing-dependent complementation. Because of the low transcriptional start site of a gene, long-range and trans frequency of finding such complementary mutations, work interactions can also affect gene regulation (reviewed in on understanding transvection has focused on test cases in- Henikoff and Comai 1998; Dekker 2008). To understand cluding, but not limited to, the yellow (Geyer et al. -
Perspectives
Copyright 2000 by the Genetics Society of America Perspectives Anecdotal, Historical and Critical Commentaries on Genetics Edited by James F. Crow and William F. Dove Guido Pontecorvo (ªPonteº), 1907±1999 Bernard L. Cohen IBLS Division of Molecular Genetics, University of Glasgow, Glasgow G11 6NU, Scotland UIDO Pontecorvo died on September 25, 1999, and enjoy Aristophanes in Greek. During studies in the G age 91, of complications following a fall while col- Faculty of Agriculture in the University of Pisa, his inter- lecting mushrooms in his beloved Swiss mountains; he est in genetics was aroused by E. Avanzi, a plant geneti- was a signi®cant contributor to modern genetics. He cist. And in my recollection of a distant conversation, his was also an irascible yet genial friend and advisor who orientation toward agriculture resulted from working a attracted the great affection and admiration of col- relative's chicken farm when he was a teenager. Under- leagues and students worldwide and who, as head of graduate friends, among them Enrico Fermi (known department and Professor of Genetics, served the Uni- even then as ªthe Popeº because of his infallibility), were versity of Glasgow with distinction from 1945 until 1968. also in¯uential mountaineering and skiing companions. It was characteristic that in 1955, when promoted to the After two years' compulsory military service in the light newly created Chair of Genetics and also elected Fellow horse artilleryÐand somehow the image of Lieutenant of the Royal Society, he circulated a note saying that Pontecorvo exercising the commanding of®cer's horse henceforth the head of department should be known seems not at all incongruous!ÐPonte became assistant as ªPonteºÐmeaning of course no change; he was any- to Avanzi, now director of an experimental agricultural thing but pompous. -
Unifying Homology Effects Carlo Cogoni
news & views Unifying homology effects Carlo Cogoni University of Rome ‘La Sapienza’, Dipartimento di Biotecnologie Cellulari ed Ematologia, Viale Regina Elena, 324, 00161 Rome, Italy. e-mail: [email protected] Meiotic silencing by unpaired DNA is a new mechanism, related to other homology-dependent gene silencing phenomena, with implications not only for genome protection against invasive nucleic acids but for genome maintenance and speciation as well. The ability of DNA sequences to pair with A single ancient origin silencing). Based on these characteristics, each other on the basis of sequence homol- Neurospora crassa is haploid during vege- which differ from transvection as it is ogy is well recognized, being the basis for tative growth, whereas in the sexual cycle, observed in Drosophila, meiotic transvec- homologous chromosome pairing during two haploid nuclei of opposite mating tion has been renamed ‘meiotic silencing meiotic prophase. In the past decade, it has type fuse to produce a diploid cell, the by unpaired DNA’ (MSUD). Shiu et al.2 become clear that homology-based interac- zygote. The zygote immediately under- also discovered that MSUD is not tions between nucleic acids, both DNA and goes the two meiotic divisions, followed restricted to a few genes as was previously RNA, can be influential not only in accom- by one mitotic division, to produce hap- believed, but that virtually the entire plishing pairing and recombination during loid ascospores. Thus, the brief period genome is subject to this process. A note- meiosis, but also in regulation of gene after karyogamy and before meiosis is the worthy finding is that a putative RNA- expression at other times in the cell cycle.