G Model CRASS3-3451; No. of Pages 6 C. R. Biologies xxx (2016) xxx–xxx Contents lists available at ScienceDirect Comptes Rendus Biologies ww w.sciencedirect.com Trajectories of genetics, 150 years after Mendel/Trajectoires de la ge´ne´tique, 150 ans apre`s Mendel From Mendel to epigenetics: History of genetics De Mendel a` l’e´pige´ne´tique : histoire de la ge´ne´tique Jean Gayon Institut d’histoire et de philosophie des sciences et des techniques (IHPST), UMR8590, Universite´ Paris-1/CNRS/ENS, 6, rue du Four, 75006 Paris, France A R T I C L E I N F O A B S T R A C T Article history: The origins of genetics are to be found in Gregor Mendel’s memoir on plant hybridization Received 26 April 2016 (1865). However, the word ‘genetics’ was only coined in 1906, to designate the new Accepted after revision 30 April 2016 science of heredity. Founded upon the Mendelian method for analyzing the products of Available online xxx crosses, this science is distinguished by its explicit purpose of being a general ‘science of heredity’, and by the introduction of totally new biological concepts (in particular those of Keywords: gene, genotype, and phenotype). In the 1910s, Mendelian genetics fused with the Mendel chromosomal theory of inheritance, giving rise to what is still called ‘classical genetics’. Mendelian genetics Within this framework, the gene is simultaneously a unit of function and transmission, a Chromosomal theory of inheritance unit of recombination, and of mutation. Until the early 1950s, these concepts of the gene Gene coincided. But when DNA was found to be the material basis of inheritance, this Molecular biology congruence dissolved. Then began the venture of molecular biology, which has never stopped revealing the complexity of the way in which hereditary material functions. ß 2016 Acade´mie des sciences. Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/). R E´ S U M E´ Mots cle´s : La ge´ne´tique puise ses origines dans le me´moire de Mendel sur l’hybridation des plantes Mendel (1865). Le mot « ge´ne´tique » ne fut cependant introduit qu’en 1906 pour de´signer la Ge´ne´tique mende´lienne nouvelle science de l’he´re´dite´. Fonde´e sur la me´thode mende´lienne d’analyse des produits The´orie chromosomique de l’he´re´dite´ de croisements, cette science se distingue par son but explicite — eˆtre une science ge´ne´rale Ge`ne de l’he´re´dite´ —, et par l’introduction de concepts biologiques totalement nouveaux Biologie mole´culaire (notamment ceux de ge`ne, de ge´notype et de phe´notype). Dans les anne´es 1910, la ge´ne´tique mende´lienne a fusionne´ avec la the´orie chromosomique de l’he´re´dite´ pour donner ce qu’on appelle toujours aujourd’hui la « ge´ne´tique classique ». Dans ce cadre, le ge`ne est tout a` la fois une unite´ de fonction et de transmission, une unite´ de recombinaison, une unite´ de mutation. Jusque dans les anne´es 1950, ces concepts du ge`ne coı¨ncident. Mais lorsqu’on de´couvre que l’ADN est la base mate´rielle de l’he´re´dite´, cette unite´ se dissout. Commence alors l’aventure de la biologie mole´culaire qui, de 1953 jusqu’a` aujourd’hui, ne va cesser de complexifier notre connaissance du fonctionnement physiologique du mate´riau he´re´ditaire. ß 2016 Acade´mie des sciences. Publie´ par Elsevier Masson SAS. Cet article est publie´ en Open Access sous licence CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/ 4.0/). Email address: [email protected]. http://dx.doi.org/10.1016/j.crvi.2016.05.009 1631-0691/ß 2016 Acade´mie des sciences. Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/). Please cite this article in press as: J. Gayon, From Mendel to epigenetics: History of genetics, C. R. Biologies (2016), http://dx.doi.org/10.1016/j.crvi.2016.05.009 G Model CRASS3-3451; No. of Pages 6 2 J. Gayon / C. R. Biologies xxx (2016) xxx–xxx 1. Introduction: ‘Genetics’ In a letter to his colleague Adam Sedgwick in 1905, the English biologist William Bateson (1861–1926) used the word ‘genetics’ to designate ‘the science of heredity and variation’. Bateson was then known as one of the major Mendelians in the world, and proposed using the word ‘genetics’ to name the chair that was created for him at Cambridge in 1906. In the end, Bateson’s chair was named ‘chair of biology’, but on the occasion of the third International Conference on Plant hybridization, Bateson proposed that the new science of heredity based on Mendel’s laws be named ‘genetics’. This proposal was enthusiastically approved and the 1906 Conference was published in 1907 as ‘Report of the Third International Conference 1906 on Genetics’. This periodical meeting still exists. In spite of deep theoretical changes, some of which Fig. 1. Three formulae used by Mendel in his 1866 memoir for explaining are described hereafter, the scientific discipline of genetics the ratio observed of one character ([1], p. 30). The two parents belong to, has maintained itself. respectively, type A and type a (for instance yellow and green peas. A is dominant over a. The first formula represents what happens during 2. Origins of genetics: from Mendel to Mendelism fertilization: pollen cells (pollenzellen) associate with ovarian cells (Keimzellen). The four combinations represented are equiprobable. The second figure represents the result in the zygote (numerator: male origin; When was genetics born? Was it in 1866, year of the denominator: female origin). The third formula shows the proportions of publication of Mendel’s memoir on plant hybridization [1]? three types in the progeny: two pure parental forms (A and a), and one Or in 1900, when three botanists, Hugo de Vries in the hybrid form Aa. If crossed between them, these Aa will give again a mixture of pure and hybrid progeny. The second formula shows how close Netherlands, Carl Correns in Germany, and Erich von Mendel was to the spirit of genetics. But the third formula shows that he Tschermak in Austria, independently rediscovered Mendel’s did not have the notions of genotype and allele. In Mendelian genetics laws? Or in 1902 when Bateson’s book, A Defence of Mendel’s (here distinguished from Mendel), the second member of the equation Principles of Heredity explicitly connected Mendel’s laws would be: AA + 2Aa + aa. with the general question of ‘heredity’ [2]? Or in 1906, when Bateson first made public use of the word with reference to international meeting devoted to it. But this was of course Mendel? There cannot be a definitive answer to this the result of a complex intellectual history that cannot be question. Mendel’s experimental work on peas was crucial, given here in detail [3]. but only in a methodological sense. Mendel’s intention was Two additional conceptual and linguistic events should not to offer general laws of heredity, but only a ‘law of the be added to make the Mendelian phase of the history of development of hybrids’ in plants; furthermore, Mendel’s genetics clearer. One is Hugo de Vries’ use of the words memoir remained largely unknown until 1900, when his ‘pangenesis’ and ‘pangene’ in a book published in 1889 as ‘laws’ (plural instead of singular) were rediscovered. This Intracellular Pangenesis [4,5]. In this book, De Vries rediscovery would also be an ambiguous date of birth for supported the existence of hereditary particles in all the genetics, because those who rediscovered it did not intend cells of an organism. For these particles, he coined the word to propose general laws of heredity either, but only of ‘pangene’, a word inspired by Darwin’s ‘pangenesis’, hybridization. Bateson’s 1902 book was certainly a key although De Vries’ pangenesis rejected the Lamarckian event, because it showed that Mendel’s first law (the law of part of Darwin’s hypothesis, namely the conjecture that all segregation, applying to just one character) applied not only the cells of an organism propagate little pieces of their to plants but also to animals; Bateson also defended that the cytoplasm (‘gemmules’) that circulate through the body Mendelian laws of hybridization did not apply only to the and are finally kept in the germinal cells. The term results of crosses between individuals of distinct varieties or ‘pangene’ is the origin of Wilhelm Johannsen’s ‘gene’, species, but to a huge number of individual hereditary proposed in 1909 in the important book where he also differences among virtually all sexually reproducing orga- introduced the words ‘genotype’ and ‘phenotype’ nisms. This book also introduced a technical vocabulary that [6]. Johannsen was responsible for the standard meaning rapidly became indispensable for all Mendelians: ‘allelo- of the ‘term’ gene that dominated until the emergence of morph’ (or, more simply, ‘allele’), ‘homozygote’, and the molecular concept of the gene: no more than a ‘heterozygote’; these terms imply that for a given character ‘calculating unit’ intervening in Mendelian crosses, with no transmitted in a Mendelian way, each individual has two morphological hypothesis about the nature of the Mende- (and exactly two) physical versions of the same hereditary lian determinants. element — an idea that Mendel did not suggest (Fig. 1). Finally, 1906 would be too late a birth date, because a 3. Incorporation of knowledge on chromosomes into significant international community of Mendelians already genetics: classical genetics, 1915–1950 existed by then.