Variability

VARIABILITY. The problem of organic evolution raised in the 19th century directly confronted biology with the question of the nature of the changes that serve as the basis for the emergence of new forms in the evolutionary process. Lamarck, who was the first to clearly articulate the idea of the gradual replacement of forms over time, saw the cause of occurring changes in the direct influence of the changing external environment, from epoch to epoch, from one habitat to another. He believed that, acting from generation to generation in the same direction, new conditions of existence produce (in plants directly, and in animals through their changed habits, prompting exercise or, conversely, disuse of certain organs) changes that gradually become fixed and become the hereditary property of the species. Lamarck's concept requires that the organism's reactions to changes in external conditions be purposeful, otherwise the obvious adaptation of living forms to their surrounding environment would not be explained. Darwin's theory of the origin of species overcomes this difficulty by introducing the concept of selection—natural in nature and artificial in cultural conditions—which allows only individuals with useful changes in the struggle for existence or desirable changes for breeders to survive and reproduce. The state of science at that time did not make it possible to draw a sharp line between hereditary and non-hereditary variability, although Darwin clearly understood that only the former could serve as suitable material for selection. Darwin saw the cause of changes in the same factors of the external environment as Lamarck, and to explain their hereditary transmission he constructed the now completely meaningless 'temporary hypothesis of pangenesis.' In the period following the publication of Darwin's works in the 19th century, researchers' attention focused on the problem of heredity and, in particular, the transmission of properties acquired under the influence of external conditions. However, it was not these theoretical disputes and speculative theories of heredity associated with the names of Nägeli, de Vries, and Weismann that brought the necessary clarity to the problem of the evolutionary significance of various changes, although the concept of carriers of hereditary traits contained in the cell nucleus (Darwin's gemmules, de Vries' pangenes, Weismann's determinants) that gained firm footing in science thanks to them, and the almost finally (in a negative sense) resolved question of the adequate inheritance of acquired properties, played an essential role in the further study of variability. The stimulus for further development of the problem appeared on the threshold of the 20th century in the form of new facts and experimental data that forced a reconsideration of the previously prevailing views. In 1894, the book 'Materials for the Study of Variability, Discussed Especially from the Point of View of the Discontinuity of Species' by the English biologist Bateson was published, in which the author presented a huge number of cases of discontinuous variability of traits, in particular a series of examples of so-called meristic variation, i.e., changes in the number of repeatedly occurring organs (for example, fingers, vertebrae, etc.), and pointed to the possible role of such deviations in the evolutionary process. In 1900, Korzhinsky published a study entitled 'Heterogenesis and Evolution,' in which, based on facts drawn from horticultural and botanical literature, he proved the existence of so-called heterogeneous variations—sharp and sudden, moreover hereditary deviations—and defended their evolutionary significance. Finally, in 1901, the Dutchman de Vries published a two-volume work entitled 'The Mutation Theory,' in which two kinds of variability were clearly distinguished. 1. Modificational, or fluctuating, variability, often simply called variation, expressing itself in small, continuous quantitative deviations from the average size of a trait, resulting from the influence of the external environment and not hereditary in nature. 2. Mutation variability, consisting of sharp deviations from the norm, having no gradual transitions to the original trait, transmitted by inheritance and fully coinciding with the heterogeneous variations of Korzhinsky. In contrast to Darwin, who emphasized variability of the first kind, de Vries particularly stresses the evolutionary significance of mutation variability and conceives of evolution as a discontinuous process with the abrupt and timed to special 'mutation periods' formation of new species. De Vries built his theory on facts from the field of plant variability. The plant Oenothera Lamarckiana of the Onagraceae family, brought from America to Europe, played a particularly important role in this, which year after year gave a series of mutations—gigantic (gigas), dwarf (nanella), broad-leaved (lata), with a short pistil (brevistilis), and a number of others. Soon, the classification of variability given by de Vries received experimental verification and confirmation in the classic works of another major biologist—Johannsen. The latter established that in beans bred by self-pollination, and therefore unchanged in their hereditary composition, 'pure lines,' traits (for example, seed weight) fluctuate around a certain average specific to each 'biotype,' and selection is powerless to influence the change of this last. However, occasionally the average value suddenly shifts, and this may be explained by a qualitative change—a mutation (in this case so-called stepwise) in the hereditary structure, or genotype of the line. Hence mutation variability also received the name genotypic, in contrast to non-hereditary, concerning only the external appearance, phenotypic fluctuations. Almost at the same time, the works of Mendel were rediscovered, clarifying (as early as 1866) the laws of inheritance of traits, and from this moment the study of mutation variability entered as a component part into genetics. Data on the occurrence of mutations significantly enriched, and mutations themselves were found in enormous numbers everywhere researchers turned their attention. In particularly large numbers, mutations were found in plants: snapdragon (Antirrhinum), four-o'clock (Mirabilis jalapa), corn, datura, then in peas, cereal grains, tobacco, and many other plants. Among animals, vertebrates provided a huge number of facts: rabbits, guinea pigs, rats, mice, various agricultural animals, chickens, live-bearing fish. Man was no exception in this respect. The study of insects proved particularly fruitful, among which the fruit fly, Drosophila melanogaster, served as an excellent experimental object first for the American scientist T. Morgan and his students—Bridges, Muller, and Sturtevant, and then for researchers worldwide, including Russians. In 1926, over 400 mutations were already counted in this fly, and since then this number has increased enormously and cannot be accounted for. The study of mutations by genetic methods showed that they are due to various changes in the chromosomes contained in the cell nuclei. At the same time, mutations can be caused (in the vast majority of cases) by some change in the hereditary factors or genes arranged in linear order along the length of the chromosomes—so-called local mutations, or transgenations (point mutations—English authors), or they are caused by changes in the number of chromosomes and various rearrangements of their sections—so-called chromosomal abnormalities. These include polysomies (mono-, di-, tri-, etc. somic mutations), or the addition of one, two, three chromosomes to the normal set, polyploidy, or multiple multiplication of the haploid number of chromosomes (triploidy, tetraploidy), translocations, i.e., the movement of a piece of one chromosome to another, duplication (duplication) or reversal (inversion) of entire sections, loss, or inactivation of sections (so-called deficiency), fusion of chromosomes with each other (association) or, conversely, their fragmentation, etc. The term genovariations proposed by the Russian geneticist S. Chetverikov is convenient and is acquiring more and more rights, allowing to distinguish genetic mutations from the mutations of the paleontologist Waagen, who calls by that name the successive changes of organic forms in geological strata. At present, it is believed that both transgenations and chromosomal aberrations can serve as material for the evolutionary process. Among the latter, polyploidy and polysomies (and perhaps to a lesser degree duplications and loss of sections) probably play an outstanding role (especially in plants), which is evident from the fact that in some genera (for example in chrysanthemums, roses, sorrels) close species have multiple numbers of chromosomes, in other genera (for example in many lilies) close species have numbers of chromosomes differing by 1, 2, 3, etc., and also from the fact that crossing a tetraploid mutant form with the original diploid turns out to be infertile, as in the case of crossing 'good' Linnaean species. Transgenations probably constitute the bulk of mutations with which natural selection deals.

Recessive mutations that arise in nature must pass into a hidden (heterozygous) state, which, as Chetverikov showed, leads to the saturation of natural species with genes that do not manifest externally. Only upon reaching significant saturation or under natural or artificial (under experimental conditions) isolation does the probability of homozygous individuals for a given gene arise, and the mutation is subjected to the action of negative or positive (depending on its usefulness) selection. Divergence of species differing in local (geographical) mutations is possible only under the condition of geographical or other isolation, allowing the separated communities to diverge to a complete or partial inability to produce fertile offspring (physiological isolation). Mutations can affect any traits to any degree. Often they change one particular trait sharply, but at the same time they are reflected to some degree, however slight, in others (pleiotropy). They can affect such essential traits and functions that the mutant becomes non-viable (lethal mutations), but they can also be the basis of such insignificant quantitative deviations (e.g. in the case of single and multiple factors or when the trait is sensitive to any changes in the genotype) which externally do not differ from modifications. Besides the occurrence of genetic variations, the process of creating new species can probably have as its source combinatorial variability, occurring during the crossing of races, varieties, and close species, leading to the regrouping and new combination of inherited characteristics of the original forms in the hybrid. Gerald indicated such a possibility for animals using the example of a number of insects, particularly the day-flying butterflies Colias. The botanist Lotsy, based on facts observed in the plant world, viewed all evolution as the emergence (through the crossing of species) of new combinations of hereditary rudiments that already existed in several original 'primary plasmas' without any new hereditary factors arising. Lotsy's theory of evolution is not currently recognized. The role that one or another type of V. plays in the evolutionary process is currently difficult to determine. Only certain moments of the speciation process are clear so far, while the comprehensive picture is a matter for the future. As for the causes that give rise to mutations, this question has remained obscure until recently, and only in the last few years has some light begun to be shed on it. For a long time it was believed that the occurrence of mutations (local, since chromosomal abnormalities are due to various, often externally influenced, e.g. anesthesia, cooling, etc., irregularities in mitosis) was subject to microcosmic forces little understood by us, inevitably causing the restructuring of a gene in a certain, small, but stable percentage of cases. The mutating process seemed as independent of human intervention as the process of radioactive decay. The situation changed sharply when in 1927 Muller succeeded in accelerating the mutation process in Drosophila almost 150 times by using X-rays as the affecting agent. The mutations he obtained did not differ in any way from those that had occurred previously, except for the relatively much higher percentage of chromosomal aberrations and lethals. Following Muller, X-rays, and then gamma rays of radium, were used with equal success by a number of researchers (including in the USSR by Serebrovsky). It was found possible to obtain mutations not only in Drosophila but also in other objects, e.g. tobacco, datura, as well as reverse mutations of changed genes back to the original normal state, which occurs naturally extremely rarely. Besides gametic mutations, arising in the cells of the germ line and thus passing into the gametes and with them into all somatic and sexual cells of the offspring, X-rays and radium have succeeded in causing a large number (previously known) mutations in the somatic cells of the developing organism. Such somatic mutations manifest themselves only in tissues derived from the mutated cell, which in animals leads to the formation of mosaics, and in plants to the appearance of mutation shoots known even to Darwin (bud mutations). At present there is an attempt to explain the natural mutation process by the influence of the earth's radioactive radiation. Babcock and Collins made an interesting attempt to show that the rate of the mutation process in different parts of California corresponds to the intensity of the earth's radioactive radiation in the same places. Finally, the search for natural causes that produce mutations promises to end with the inclusion of such a universal factor as temperature fluctuations in their circle, if the experiments of Goldschmidt are confirmed, who reported in 1929 that the action of temperature 37° on Drosophila larvae results in an extraordinary increase in the frequency of mutations, far exceeding even the experiments with X-rays. Some cases of heritable V., upon closer examination, turned out to be only temporary, albeit very stable, long-term modifications (M.).

b.

Astauruv. Methods for the Study of V. Since the appearance in 1859 of Darwin's 'Origin of Species,' which put the doctrine of the variability of organisms and natural selection at the foundation of his theory of evolution, the question of variability has become one of the main questions of general biology and its applications in agriculture and medicine. The greatest credit for the modern study of the phenomena of variability belongs to English and American scientists who applied precise statistical methods to this field (see Biometrics). The journal 'Biometrica,' founded in 1901 by Galton, Pearson, Weldon, and Davenport, is a most valuable collection of quantitative data on the variability of plants, animals, and humans. In the USA, a prominent role in this movement belongs to Raymond Pearl, professor of biometry and vital statistics at Johns Hopkins University. - The main characteristics of V. of any countable or measurable trait are the arithmetic mean, the standard deviation, and the coefficient of variation (see Variational Statistics). The elementary methods of their calculation are as follows. Let us suppose that the hooks on the hind wings of 100 bees have been counted. The following numbers were obtained: 21, 20, 18, 19, 17, etc. One can count how many bees had 18 hooks, how many had 20, etc. Having done this, one obtains the so-called variational series. Number of hooks in the wing...... Number of bees with this number of hooks ........ 18 19 20 21 22 23 24 25 2 5 10 22 24 17 12 3 To obtain the arithmetic mean of the number of hooks of the variational series, one must multiply the numbers expressing the magnitude of the trait by the number of cases, add the products, and divide by the total number of cases. In this example M (arithmetic mean) will be as follows: TJ-- 2.18+5.19+10.20+22.21+24.22+17.23+12.24+8.25 = 22,00. Besides the question of the arithmetic mean, which gives the center of distribution of individual variants (in the simplest case), the question arises as to the degree of scattering of variants around the type (arithmetic mean). The standard deviation gives the answer to this question. The calculation proceeds as follows. Let us take in this example bees with 18 hooks. Each is 4 hooks away from the type (18 - 22 = -4). Squaring this deviation gives 16 hooks, and since there were two such bees, we take 16 twice. The same operation is performed for all classes, and after summing, divide by the total number of cases-100. One obtains the mean square deviation, and taking its square root, one obtains the quantity called the standard deviation (deviation from type) and denoted by the Greek letter sigma (σ). The entire calculation will take the following form: /"16.2+9.5+4.10+1 .22 + 1 .17+4.12+9.8 _b_ _± y ----------_ш------------=, = ±1/2776 =±1,661 hooks. Sigma is a named quantity and is expressed in the same units as the trait being studied. To enable comparison of the variability of traits expressed in different units (e.g. to compare V. of human weight with his height, etc.) and giving variational series with different M values, an abstract characteristic was devised. It is found by expressing sigma as a percentage of the arithmetic mean given i

s.r.i 100. a 1,661.100 of the series according to the formula: C% = -d|-° ^ = = 7.54%. In cases where our traits are expressed by measurements, for example, in the case of studying the variability of growth, for the sake of clarity, it is necessary to combine them into classes and, when calculating the characteristics of the series, relate the number of cases in a class to the midpoint of the class. It must be pointed out that besides the possibility of studying the variability of traits separately, one can study how they are connected with others—the coexistence of traits. A rational classification of the phenomena of variability is quite complex, as the most diverse principles can be taken as its basis. The fundamental division must still be considered the division of variations into hereditary and non-hereditary—genovariations and phenovariations according to Johannsen. The former are determined by differences in hereditary germ plasm, the latter by the development of organisms under different conditions. The second major subdivision of the phenomena of variability is the division of variability into individual and group (Johannsen). An example of the former can be the variation within, for example, one family of the same bees. The latter, i.e., group variability, is such that we are dealing with differences characterizing groups of individuals. The coefficient of variability is one of the main characteristics of individual variability. As an example, the coefficient of variability of various traits in humans, according to Pearl (1923), is given. Traits: Male, Female. Skin sensitivity: 35.70, 45.70. Body weight (in Bavarians): 21.32, 24.715. Brain weight: 8.118, 8.340. Femur length: 5.05, 5.04. Height (in the English): 3.99, 3.83. Longitudinal diameter of the skull (in the English): 3.31, 3.45. Skull circumference (in the English): 2.87, 2.92. Group variability can be subdivided into family, ecological, temporal, and geographical variability. Family variability (Alpatov, 1924) is an elementary type of group variability. If one calculates the arithmetic means for individual families of a given animal, one can discover that each family will be characterized by its own expression of its type. In family variability, the main factor determining it is heredity. As proof of this, one can cite the data of the Danish scientist J. Schmidt (J. Schmidt), who studied the number of vertebrae in the offspring of individual females of the viviparous fish, the eelpout, which is also found in our waters off the coasts of the Baltic, Barents, and White Seas. For the results of the survey, see the table on the next page. These data show with perfect clarity the dependence of the average number of vertebrae of the offspring on the number of vertebrae in the mothers. As an example of variability

198 Number of vertebrae in the mother, Number of mothers studied, Average number of vertebrae in offspring: 116.30, 115.62, 114.79, 114.15, 113.85, 113.51, 113.12, 112.95, 112.52, 111.60, 112.40, 111.40, 109.25. As an example of ecological [variability], one can cite the same eelpout fish. Using the example of the fjords of Denmark in particular, Schmidt was able to show that the average number of vertebrae of the population of a given section of a fjord stands in close connection with salinity. The fresher the water, the smaller the average number of vertebrae. The smallest number is found in fish living in the depths of the fjord, the largest in fish of the open sea. Specially designed experiments on transplanting fish in specially constructed wire cages from points with one salinity to points with another showed that the offspring of the transplanted mothers retain their traits without change. This proves the heredity of the traits of ecological races. As an example of temporal races (temporal races, Alpatov, 1924), one can cite the existence among herring, for example, of the Baltic and North Seas, of groups of individuals appearing at the coasts for spawning in different seasons of the year. Thus, they distinguish spring and autumn herring, characterized, besides the time of reproduction, also by a number of morphological traits. In the seas, it is sometimes difficult to distinguish ecological variability from geographical. The ichthyologist Heincke cites the numbers of vertebrae of herring and flounder in different seas. Flounder, Herring, Baltic Sea...

42.5

43.0

57.0. In this table, the seas are arranged in order of increasing salinity, and the number of vertebrae in the fish increases in parallel with the salinity. Terrestrial animals also show numerous examples of geographical variability. The honeybee, in its distribution throughout the European part of the USSR, provides a beautiful picture of the change in traits from north to south. According to the idea expressed by the scientist and beekeeper Mikhailov (1924), the increase in the length of the proboscis of the worker bee toward the south is connected with the fact that in the south, the nectar in flowers is located lower than in the north, and the bees have to have a longer proboscis to reach it. It is interesting to note that the overall body dimensions of the bee decrease toward the south, and the coloration of the abdomen becomes yellower. Studies on European breeds of bees brought to North America (Alpatov, 1929) showed that the differences by which they are characterized in Europe are preserved after living for a number of generations in the New World, thus proving the heredity of the differences of geographical races. In conclusion, it must be noted that the difference between races is not limited only to morphological traits. Differences in chemistry, physiology, and biology are connected with them. This concerns animals and plants as well as humans.

V. Alpatov. Microbial variability-a term denoting the observed changes in microbes that occur in their structure or their biological properties both during their reproduction and during their conservation. Such changes are observed under natural conditions of microbial life, but can also be artificially induced. The general term variability (variability) does not prejudge the question of the depth, extent of changes, constancy and duration of the process (modifications, mutations).-History of the question. The question of microbial variability was first raised in 1877 by Nägeli. However, this idea was disputed at the time by Colin, who considered that the microbial form is constant and does not undergo variability (monomorphism). Colin was supported by Koch, who with his authority for many years did not allow the opposite viewpoint (pleo- and polymorphism) to develop. However, the phenomena of microbial variability, both morphological and biological, were so obvious in daily laboratory work that a number of authors (Mechnikov) already considered it a fact by the end of the 19th century. But certain data were needed to refute the doctrine of the constancy of microbial species. The first significant impetus was given in 1905-06 by the works of Neisser and Massini, who described Bact. coli mutabile with colonies of the microbe on Endo agar of different colors, i.e. with different biochemical properties. Subsequently, through the works of Zlatogorov, Baerthlein and Almquist, it was proven that microbes change morphologically and in colony structure and in antigenic relation, for example losing agglutinability (1907-1911). At that time, the causes of such variability were not assumed to be in the complexity of the structure of the microbial culture, since experimental confirmation of this was first given in 1916-1917 by the works of Weil and Felix, who split the X₁₉ culture into H and O forms and proved the existence in it of a 'double' antigenic apparatus. From this grew the doctrine of splitting, or dissociation of microbes ('microbic dissociation'). A strong impetus to this doctrine was given by Arkwright (1921) and Hadley (1926), who proved that microbial cultures consist of individuals that give on a solid nutrient medium 2 different types of colonies: S (smooth)-smooth and R (rough)-wrinkled (see Microbial dissociation). The colonies differ not only in external characteristics but also in various biochemical and biological properties. Hadley (1928) already speaks of the dissociation of each culture, in which he distinguishes S, R, O forms and bacteriophage. Thus, one must consider that not only each microorganism is capable of variability, but that the latter is also connected with the composition of cultures in which a number of individual forms preexist.-Character of variability. To this day, there is still a dispute as to how profound these changes in microbes are and whether one can speak of mutations in the microbial world. This question has great practical significance and many works are devoted to it. These changes in microbes concern both morphological and biological and serological sides.-What is the scope of these changes? Can one now in the field of microbial morphology follow the path of Enderlein, i.e. consider that the most diverse forms of microbes are stages in the development of one microbe (cyclogeny)? To this question one must for now answer negatively and consider that there is a limit for morphological variability of microbes. Thus, the basic coccoid forms of the microbe do not turn into a spirilla: one cannot admit the possibility, for example, of a yeast cell turning into a spirilla or a diphtheria bacillus into a streptococcus. However, as for morphological variability, it is currently considered that fluctuations are possible in much wider limits than was previously admitted. Thus, the ability to stain according to Gram in some cases (gonococcus) can change, and the presence of filterable forms in most microbes indicates great morphological variability. The biochemical properties of microbes can change greatly: microbes either lose the ability to break down carbohydrates etc. (group of dysentery bacilli) or acquire new properties (Bac. subtilis, Streptococcus). The same must be said of antigenic properties in the processes of immunity. Sometimes the microbe loses the ability to agglutinate (experiments with cholera vibrio), sometimes microbial cultures that did not previously possess this property begin to agglutinate [cultures of Bac. proteus X₁₉ with typhoid sera, cholera vibrios and some other microbes after staying in a filtrate from organs of scarlatina patients-with scarlatina serum or convalescent serum (Martin, Laffaille)]. Especially striking are the facts of variability when microbes, previously little pathogenic or saprophytes, subsequently acquire pathogenic properties. The acquisition of pathogenic properties by saprophytes has been proven experimentally, as well as the increase in virulence in microbes that were in a latent state. Collecting these scattered facts, one must admit that within the limits of a microbial family the transition of one species or subspecies to another is experimentally proven. This applies to the typhoid-intestinal group, the pneumo-, streptococcus group, hemorrhagic septicemia etc. (see also Species in microorganisms).-Causes of variability are divided into internal, inherent in the biological essence of the microbe, and external, connected with the environment. Internal causes have as their basis the instability of the colloidal complexes of protoplasm. The reaction of the medium, excess of certain substances (for example carbohydrates and water), their deficiency (starvation), products of metabolism of microbes, enzymes, poisonous substances, temperature, dyes, oxygen, X-rays and radium rays (Nadson)-all these are factors causing variability. To these factors must be added the stay of microbes in an immune environment, cohabitation with other microbes and external impulses, such as activation of the macroorganism in which the microbe lives. Finally bacteriophage (see Bacteriophagy) also contributes to microbial variability.-Variability and dissociation of microbes have great significance for explaining various pathological processes and for resolving various epidemiological problems. Thus, only by recognizing the phenomena of variability can one understand the revival of microbes de sortie and the origin of new infections. The laws of development and extinction of epidemics also receive illumination from the point of view of the doctrine of microbial variability. First comes the strengthening of the microbe, the splitting off of virulent races, and then under the influence of the immunizing organism the transition S to R occurs, and the epidemic ceases. Finally, the doctrine of variability also sheds light on the phylogenetic connection between various microbial groups. The observations of Zlatogorov and Mogilevskaya showed that by splitting cultures of false tuberculosis of rodents, one can prove the close relationship of the false tuberculosis bacillus with the plague bacillus. The doctrine of the splitting of cultures is also fraught with large purely practical results: it will be necessary to revise the methods of active immunization and use for this purpose the most active dissociated races of microbes. Zlatogorov. Coefficient of variability, see Variational statistics.