Trajectories of Genetics E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 459

Veröffentlichungsjahr: 2020

Beschreibung

As genetics becomes increasingly important in our everyday environment, misinterpretation of its scientific foundation leads to mixed feelings of hope and fear about the potential of its applications. Trajectories of Genetics uncovers the many facets of genetics - from humans to animals, plants, and the microscopic world through more than a century of scientific progress. It summarizes the evolution of ideas as the organization and functioning of genetic material has become clearer. The book analyzes how genetic information – transmitted from generation to generation in nucleic acids – enables the fulfillment of biological functions and the evolution of the living world. It illustrates current developments in many areas: the improvement of species of agronomic interest, an increased understanding of microbial worlds, the management of genetic pathologies and the synthesis of new forms of life.

Leseprobe

Table of Contents

Cover

Introduction

1 Following Ariadne’s Thread from Genetics to DNA

1.1. The birth of genetics

1.2. The foundations of a new science

1.3. Gene, locus and genetic maps

1.4. Mutagenesis, first ideas on the material nature of the gene

1.5. First ideas on gene products

1.6. The order of things and the elements of disorder

1.7. Dissecting the invisible: allelism, cistron and the locus again

1.8. The DNA trail

1.9. Important ideas to remember

1.10. References

2 The Molecular Nature of Genes and Their Products

2.1. DNA and its replication

2.2. Permanence and alteration of DNA, mutations

2.3. Protein synthesis and the central dogma of molecular biology

2.4. The genetic code: how to read the genetic message

2.5. First paradigm of gene expression: the bacterial lactose operon

2.6. Reverse transcription and retrogenes

2.7. Exons, introns and splicing: the first complexity of RNA life

2.8. Sequence editing: the second complexity of RNA life

2.9. RNA interference and epigenetics

2.10. Important ideas to remember

2.11. References

3 Chromosomes and Reproduction

3.1. The “true” chromosomes

3.2. Sexual reproduction and alternating generations

3.3. Meiosis

3.4. Genetic determinism of sex

3.5. Clonal reproduction and its derivatives

3.6. The genetics of organelles

3.7. Important ideas to remember

3.8. References

4 From Genetic Engineering to Genomics

4.1. Restriction of DNA

4.2. Recombinant DNA and the birth of genetic engineering

4.3. Sequencing of biological macromolecules

4.4. The beginnings of genomics: the very first genome sequences

4.5. The trigger

4.6. The impact of the first real genomes

4.7. The human genome

4.8. New methods of genome sequencing and the current state of genomics

4.9. Important ideas to remember

4.10. References

5 Uniqueness and Polymorphism of Genomes

5.1. The immensity of nucleic acid sequences

5.2. Components of genomes and their replication

5.3. A little perspective on the content of genomes

5.4. Traces of the past and driving forces for the future

5.5. Genes in genomes

5.6. Genes and genetic determinism

5.7. Natural populations: pan-, core-genomes and SNP

5.8. Population genomics

5.9. The genetics of genomes

5.10. Important ideas to remember

5.11. References

6 Natural Dynamics and Directed Modifications of Genomes

6.1. The dynamics of genomes

6.2. Hereditary acquisitions

6.3. Directed manipulations of genomes: principles and tools

6.4. Directed manipulations of genomes: applications

6.5. Important ideas to remember

6.6. References

7 Of Genes and Humans

7.1. Ancient DNA and human history

7.2. Traces of the past in today’s human genome

7.3. Traces of past climates in the trees of our forests

7.4. The domestication of cultivated plants

7.5. Selection of livestock

7.6. Conclusion

7.7. Important ideas to remember

7.8. References

8 Genetics and Human Health

8.1. “Mendelian” and multifactorial diseases, a continuum of complexity

8.2. Interpretation and use of DNA sequences

8.3. Autism

8.4. Gene therapy

8.5. The multiple genetic causes of cancers

8.6. Microbiota

8.7. Important ideas to remember

8.8. References

9 Now and Tomorrow

9.1. A living world to be further explored

9.2. Genome synthesis

9.3. New lives

9.4. Important ideas to remember

9.5. References

Conclusion

C.1. Risk and the perception of risk

C.2. Ethics and genetics

C.3. References

Glossary

References

Index

End User License Agreement

Guide

Cover

Table of Contents

Begin Reading

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Series Editor

Marie-Christine Maurel

Trajectories of Genetics

Bernard Dujon

Georges Pelletier

First published 2020 in Great Britain and the United States by ISTE Ltd and John Wiley & Sons, Inc.

Apart from any fair dealing for the purposes of research or private study, or criticism or review, as permitted under the Copyright, Designs and Patents Act 1988, this publication may only be reproduced, stored or transmitted, in any form or by any means, with the prior permission in writing of the publishers, or in the case of reprographic reproduction in accordance with the terms and licenses issued by the CLA. Enquiries concerning reproduction outside these terms should be sent to the publishers at the undermentioned address:

ISTE Ltd27-37 St George’s RoadLondon SW19 4EUUK

www.iste.co.uk

John Wiley & Sons, Inc.111 River StreetHoboken, NJ 07030USA

www.wiley.com

© ISTE Ltd 2020

The rights of Bernard Dujon and Georges Pelletier to be identified as the authors of this work have been asserted by them in accordance with the Copyright, Designs and Patents Act 1988.

Library of Congress Control Number: 2019956925

British Library Cataloguing-in-Publication DataA CIP record for this book is available from the British LibraryISBN 978-1-78630-533-6

1Following Ariadne’s Thread from Genetics to DNA

In order to make natural history a true science, we must focus ourselves to research that can reveal, not the individual and particular aspect of one animal or another, but the general process by which nature reproduces and preserves itself.

So wrote Pierre Louis Moreau de Maupertuis in 1752 (Moreau de Maupertuis 1752) more than a century before the beginning of genetics.

The natural sciences have long been interested in describing the diversity of species before considering the mystery of this commonplace feature of life that makes individuals of one species generate other individuals of the same species. While genetics met the recommendation of P. Maupertuis, the path taken by scientists to develop this science was, as we will see, more like a labyrinth than a Roman road!

1.1. The birth of genetics

In 2016, genetics turned 110 years old (Gayon 2016). This term was first introduced publicly by Bateson at the Third Conference on Plant Hybridization held in London in 19061, exactly 40 years after Mendel’s publication (Mendel 1866), which had been poorly distributed and very generally misunderstood because it represented a methodological and conceptual break with everything that had existed before. However, in the century preceding Mendel’s work, botanists and horticulturists observed many offspring of plant crosses. Thomas A. Knight, at the end of the 18th Century in England, crossed pea varieties differing in seed and leaf colors and observed their offspring, but without having the idea of counting the different types obtained. In France, by hybridizing melons differing by several characters, Augustin Sageret in the 1820s had the first intuition concerning the discontinuous nature of heredity, in opposition to the vision of heredity by mixing, like two fluids, the dominant idea of the time. He wrote:

It appeared to me that, in general, the similarity of the hybrid to its two ancestors does not consist in an intimate fusion of the various characters specific to each, but rather in an equal or unequal distribution of these same characters.

At the beginning of his memoir, Mendel (see Box 1.1) justifies the literally “monastic” work that he had done during the eight preceding years by the desire “to follow up the developments of hybrid progenies” in ornamental plants. The first part of the memoir on pea hybrids (Pisum sativum) is a real experimental demonstration that ends with a kind of theorem:

Hybrids produce ovular and pollen cells that correspond in equal number to all constant forms resulting from the combination of traits brought together by fertilization [which produced this hybrid].

In other words, the stated rule is simple: a hybrid that has received from one parent the form “A” and from the other the form “a” of a given character, will produce gametes* “A” and “a” in equal numbers, A and a being mutually exclusive in these gametes, hence their name “allelomorphs2”. This law is currently known as the “law of purity of gametes” or “Mendel’s First Law”. He continued:

This proposal provides a sufficient explanation of the diversity of forms in the descendants of hybrids as well as of the numerical relationships we observe between them.

Indeed, this simple equality explains the different types of plants and their proportions in the progeny of the pea hybrids that he had produced either by self-fertilization or by back-crossing with each of their parents3. Mendel systematically found the same proportions for the seven differential traits he followed, for which there are two contrasting states and only two, such as two colors (yellow/green) or two seed shapes (smooth/wrinkled), two pod shapes (uniform/strained), two plant sizes (high/dwarf), etc.

Box 1.1.Gregor Johann Mendel (1822–1884)

Gregor Johann Mendel was born on July 20, 1822, on the family farm in Heinzendorf in what is now the Czech Republic. He received elementary education in the village school where the teacher encouraged his parents to make him continue his studies in high school, which he did excellently from 1834 to 1840. In 1838, the family situation became more precarious after a serious accident prevented his father from working. However, Mendel continued his studies at the Institute of Philosophy in Olomouc for two years, then entered the monastery of Saint Thomas in Brno (Order of Saint Augustine) as a monk in the hope of becoming a teacher by completing his training at the monastery’s expense. He was admitted to the novitiate in 1843, chosing Gregor as a first name, before being ordained priest in 1847, appointed parish priest in 1848 and assistant professor in 1849. In 1851, he went to study mathematics and physics at the Vienna Institute of Physics (Christian Doppler) and deepen his knowledge of entomology, paleontology, botany and plant physiology. Upon his return to Brno in 1854, he began his experiments on plant hybrids while teaching natural sciences and physics. The city of Brno and its monastery, then ruled by Abbot Napp, offered a particularly rich intellectual environment. In particular, the monastery was engaged in reflections on heredity, with objectives of application to sheep breeding and to the orchards of its domains.

Mendel had been interested in gardening and flowers since childhood. For example, he produced a variety of fuchsia that bears his name, and an original variety of peas from his hybridizations. He made crosses of pear, apple and cherry trees for the monastery’s orchards and even obtained a medal for his stone fruit varieties. He bred white and gray mice and crossed them to follow the heredity of coat color, a task he could not pursue within the monastery. Throughout his life, he was fascinated by bees, practicing beekeeping and their selection. He had a strong reputation in the country as a meteorologist, taking an interest in sunspots and taking precise and regular measurements until the day before his death. He had the opportunity to travel, going to Paris and London in 1862 (without being able to meet Darwin, absent at the time), to Germany, to the Alps, and to visit the Pope in Rome.

In 1868, he was appointed abbot at the head of the monastery, and recognized as an excellent teacher, an esteemed botanist and a highly valued citizen in the city of Brno. Part of his activity consisted in managing and inspecting the different dependences of the monastery. He had disputes with the government that was trying to tax monastic property. He was a member of many learned societies, curator of the Institut des sourds et muets (an institute for the deaf and mute) and, towards the end of his life, President of the Moravian Mortgage Bank. He died on January 6, 1884, as a result of kidney disease. His funeral was attended by a large crowd, paying tribute to a man highly appreciated by his fellow citizens, but unaware of his scientific contribution to biology. His successor at the head of the monastery burned his archives.

Often cited by other scientists as early as 1867, his demonstrations were generally misunderstood until the early 20th Century.

We now know that this rule corresponds to the mechanism of this particular cell division called meiosis* that halves the number of chromosomes to form gametes (see Chapter 3). In Mendel’s time, the existence of chromosomes was unknown. They were described in 1875 by Eduard Strasburger (Strasburger 1875) and named in 1888 by Heinrich-Wilhelm Waldeyer-Hartz (Waldeyer 1888). Walther Flemming (Flemming 1879) described their movement and distribution between the two daughter cells during mitosis* in 1879, but it was Edouard Van Beneden who, in the Parascaris equorum nematode, first described meiosis in 1883 (Van Beneden 1883). The individuality and continuity of chromosomes during development were demonstrated by Theodor Boveri between 1887 and 1902, and it was in 1903 that Walter S. Sutton (Sutton 1903), explicitly linked the distribution of chromosomes during meiosis in a grasshopper (Brachystola magna) to Mendel’s rule: chromosomes are distributed in pairs (like pairs of stockings!) before meiosis, and a gamete retrieves one from each pair. For a given pair, there will therefore be as many gametes possessing one member as gametes possessing the other, exactly like Mendel’s A and a factors. The gametes, in turn, after fertilization*, will reproduce an organism with the initial number of chromosomes. This is how the chromosomal theory of heredity developed, offering the first materialization on which relied, as it was said at the time, the “power to transmit some particular traits of the parents to the progenies, in addition to the characteristics of the species”.

Defined at the time by Wilhelm Johannsen as “the science of the propagation of life”, or “the science of the fixed elements that compose organisms”, genetics was to be officially born in 1900 after the rediscovery of Mendel’s work by three botanists, Hugo de Vries, Carl Correns and Erich Von Tschermak, working independently on different plant species (Campbell 1980). What became known as “Mendelism” was confirmed in mice, for coat characteristics, by Lucien Cuénot as early as 1902 (Cuénot 1902), and in humans two years later, for some cases of polydactylism, by Charles B. Davenport (Davenport 1904). It should be noted that the hereditary transmission of this trait in some families had already been described by P. Maupertuis in the 18th Century!

1.2. The foundations of a new science

Very quickly, during the first decade of the 20th Century, new concepts were developed, with the introduction of a new vocabulary. Bateson coined the terms homozygous* to reflect the fact that an individual has received the same “element” from both parents (AA or aa using Mendel’s symbolism), or heterozygous* in the opposite case (Aa or aA). We call alleles the different forms taken by the same element (A or a, but also A1, A2… a1, a2, etc.), being well aware that only two forms at most can coexist in the same organism and only one in each of its gametes. We owe to de Vries the notion of mutation, which he introduced in 1886 in studies on the appearance of new forms in the oenothera (evening primrose) that he called “mutant forms”. From 1901 onwards, he developed this new concept in relation to the work of Mendel in a famous book, including an evolutionary perspective, entitled The Theory of Mutations (de Vries 1901–1903). The term “mutation” refers to the sudden appearance, without apparent cause, of new characteristics of an organism that become heritable. The phenomenon had long been known to horticulturists, when an abnormal shoot (a sport) spontaneously appears on a tree giving, for example, flowers or fruits of a different color, without them drawing any conclusions. We will come back to this in the following chapters.

In contrast with many variations that can be found in the forms of plants, the mutants* of de Vries, which were larger oenothera known for this reason as “gigas”, had the particularity that the novel trait persisted in the progeny by self-fertilization4. He therefore saw the mutation as a mechanism that could explain the appearance of new species. It was not until 1907 that Anne M. Lutz showed that the gigas mutants were quite special, because they were plants whose chromosome numbers had spontaneously doubled (Lutz 1907). They had become polyploid* and this feature was preserved in their offspring. The term ploidy* refers to the number of chromosome sets of a cell or organism, so we have the haploid* series (one set), diploid* (two sets), triploid, tetraploid, etc. It should be noted that after doubling or quadrupling the number of their chromosomes, plants usually show only a size increase, but retain their fertility, while triplications (or odd ploidies of higher ranks) induce sterility phenomena. Sterility is sometimes useful. For example, if bananas are edible, it is because the domesticated banana trees are triploids, rendering their fruits seedless. The same applies to oysters without milt.

The idea that chromosomes show in perfect pairs had to be completed when, with the progress of cytological observation techniques, it became apparent that there was a pair of two different chromosomes in males of insects but not in females (Wilson 1905). This pair therefore seemed to determine sex (see Chapter 3). This was the first time that a characteristic could be directly assigned to a given chromosome, validating the chromosome theory of heredity5. It was only later that cytogenetics* acquired techniques to describe chromosome pairs as karyotypes* representative of a given species. In humans there are 23 pairs of chromosomes (including the sex chromosome pair), in barley 7, etc. But it is for the identification of accidental alterations of individual karyotypes* that cytogenetics has become especially useful. Thus, the presence of a supplementary chromosome in cell cultures of Down syndrome children was discovered as early as 1956, published three years later (Lejeune et al. 1959) and named “trisomy* 21” to indicate the presence of three copies of chromosome 21 (the penultimate smallest chromosome) instead of two (an example of aneuploidy*).

1.3. Gene, locus and genetic maps

Where did the idea of a gene come from? The distinction between genotype and phenotype introduced by Johannsen in 1903, mentioned in the Introduction, is fundamental because it marked an essential turning point in the evolution of ideas. Previously, these notions were implicitly confused for centuries, opening the door to beliefs about the heritability of characters acquired through the effect of the environment, with Georges-Louis Buffon, Jean-Baptiste Lamarck and even Charles Darwin, a belief that lasted until the middle of the 20th Century with Lysenkoism. In this vision, what is transmitted to the offspring by the parents are, with slight differences, “germs of organs” secreted by the organs themselves, the resemblance of the descendant to one or the other parent resulting from the dosage of these hypothetical germs from one or the other parents. Darwin, in his “pangenesis” theory, pushed this idea to the elementary structures of the organism, imagining gemmules coming from each cell that would accumulate in the gametes.

It is in this context that de Vries postulated in 1889 the existence of hereditary units, or “pangenes”, which would no longer be emanations of somatic cells, but materialistic determinants of hereditary traits that do not leave the cell (de Vries 1889). For him, “the nucleus of the cell is the pool of hereditary characters”. He made an analogy with the development of other sciences:

Just as physics and chemistry can be reduced to the study of molecules and atoms, so biological sciences must study these hereditary units in order to seek in their combinations the explanation of the manifestations of the living world.

Taking these ideas up in the light of Mendel’s work, Johannsen introduced in 1909 the simpler term “gene” to designate the fixed factors of Mendelian heredity, the “hereditary particles”. He wanted a short term totally free of any speculative hypothesis and coined this word, taken from the Greek gennao meaning “to generate” (Wanscher 1975).

It remained to be understood the nature of these genes, because when Mendel analyzed the simultaneous transmission of several different traits, he observed that they behaved independently of each other. This gave rise to Mendel’s second law, generally known as the “law of independence of characters”. Was there not a contradiction with the chromosomal theory of heredity if we assumed that two elements (now genes) that determine two traits were born by the same chromosome? Shouldn't they, contrary to what Mendel observed, always be transmitted together since they were physically linked? As early as 1906, while studying the simultaneous transmission of two traits in peas, Bateson and his colleagues (Bateson et al. 1906) observed, in the offspring of a purple-flowered (P) and long-pollen (L) line crossed with a red-flowered (p) and round-pollen (l) line, too many plants maintaining the parental associations P-L or p-l compared to the proportions provided by Mendel (9/16 and 1/16, respectively, for the second generation). They introduced the notion of genetic “coupling” to reflect this trend, erroneously interpreting it as a preferential selection of gametes reproducing the parents’ constitution.

A few years later, Thomas H. Morgan, noting the same phenomenon for the mutations of the fruit fly (Drosophila melanogaster), clarified the phenomenon known as genetic linkage*. He hypothesized that the genes responsible for the observed traits, eye color (red or white) and wing size (normal or short), were lying on the same chromosome, explaining their tendency to be transmitted together, but insisted that it is only a tendency depending on their relative distance on this chromosome. The closer the distance between the two positions (called loci*), the stronger the tendency. In other words, during gametogenesis, the two chromosomes of the same pair must exchange parts, otherwise there would be no flies of recombinant genetic constitution, different from the parents. These exchanges, called cross-over*, provide the gametes with recombinant chromosomes in which the two loci have broken their initial linkage, replaced by a new linkage (Morgan et al. 1915). But the cross-overs remained hypothetical, their existence was only revealed by the formation of recombinants between alleles of the two genetically linked loci. It was not until 1931, when Barbara McClintock