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Following 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...