Heredity and Development: Second Edition (1972)

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HEREDITY AND DEVELOPMENT: SECOND EDITION 49 3 Mendelism During the entire period from Darwin’s attempted synthesis of the facts of inheritance down to 1900, a scientific paper that was to revolutionize our understanding of heredity lay unappreciated on the shelves of many libraries. The article itself had been published in 1866. In it the author, Gregor Mendel, presented some of the results of his experiments in crossing varieties of gar- den peas. The Discovery of Mendel’s Paper. The ‘discovery’ and appreciation of the importance of Mendel’s paper is a very dramatic incident in the history of science. Three individuals in the year 1900 realized the great importance of Mendel’s work. During the 1890s there had been renewed interest in plant hybridization. The three scientists who ‘discovered’ Mendel—Hugo de Vries, Carl Correns, and Erik von Tschermak—were doing breeding experiments of their own. Each of them independently came to more or less the same conclusions that Mendel had expressed in 1866 before they knew of Mendel’s paper. This is another example of a frequent happening in science. When the field is ‘ready,’ the discovery is certain to be made. If Mendel had never lived, the history of genetics would not have been greatly different. About the year 1900, either he would be rediscovered or, had he never lived, others would reach essentially the same conclusions as he had in 1866. His work was unap- preciated in his own lifetime, for biologists in 1866 had neither the back- ground nor the prescience to understand the significance of what he had accomplished. Gregor Mendel’s famous article is not a scientific paper in the usual 

HEREDITY AND DEVELOPMENT: SECOND EDITION 50 sense, but a lecture presented to the Natural History Society of Brünn in 1865. The full results of his research were never published, but the portion that he did include, coupled with an extraordinary analysis of the data, makes his paper one of the landmarks of science. Mendel was fully aware that experiments in plant breeding had been con- ducted by many famous men. It was true, nevertheless, that no general princi- ples had emerged from previous studies. To Mendel this was a serious affair, since an understanding of inheritance was essential for an understanding of evolution and he was deeply interested in Darwin’s work (The Origin of Species appeared during the period he was conducting his experiments). He began experiments that were intended to give information on inheritance and evolution. Peas as Experimental Material. Mendel selected peas for his experi- ments because they possessed many desirable features: 1. Numerous varieties of peas were available commercially. They pro- vided the material that he studied. 2. The plants were easy to cultivate and the generation time was short. 3. The offspring of the crosses between the varieties were fertile. 4. The structure of the pea flower is such that accidental pollination was thought not to occur. The anthers that produce the pollen and the stigma where the pollen grains germinate are completely enclosed by the petals. Normally, pollen from a flower falls on the stigma of the same flower and self-fertilization results. In those cases where crosses between varieties are desired, it is possible to remove the anthers before they mature and somewhat later, when the stigma is mature, to cover it with pollen from another flower. Mendel’s approach to the problem of inheritance was different from that of previous workers. His predecessors had concentrated on the whole organism. Usually they had crossed varieties that differed in many characters and the offspring were found to be intermediate or in rare cases more like one parent. Mendel focused his attention on specific differences and studied how these were inherited generation after generation. Some of his varieties had round seeds; others had wrinkled seeds. In all he studied seven different characters of the pea, and for each he had two varieties, as shown in the following lists: CHARACTER AFFECTED VARIETIES Seed shape round or wrinkled Seed color yellow or green Seed coat color colored or white Pod shape inflated or wrinkled 

HEREDITY AND DEVELOPMENT: SECOND EDITION 51 Pod color green or yellow Flower position axial or terminal Stem length long or short Crosses of Plants with Contrasting Characters. First, he made sure that all of his varieties would breed true. Once this was established he made crosses between all of the pairs just listed. The results were most unexpected in the light of earlier experiments by other plant breeders: the offspring were never intermediate but were always like one of the parents. When peas with round seeds were crossed with peas with wrinkled seeds, for example, the offspring were plants with round seeds. Mendel spoke of the form that appeared in the offspring as dominant in comparison to the form that did not appear, which he called recessive. Dominance can be determined only by making a cross and observing the type of offspring obtained; it could not be predicted before the experiment was performed merely by examining the parent plants. The varieties that Mendel used were found to have these relationships: DOMINANT RECESSIVE round seed wrinkled seed yellow seed green seed colored seed coat white seed coat inflated pod wrinkled pod green pod yellow pod axial flowers terminal flowers long stem short stem Over the course of years, geneticists have introduced some terms that make it easier to discuss crosses. The original parental generation is abbrevi- ated P. The offspring of the P generation is the first filial or F1 generation. The offspring of the F1 is the second filial generation or F2, the third is the F3, and so on. It is also customary to describe crosses in terms of the character. Thus, the cross of a plant with round seeds with a plant with wrinkled seeds is shortened to round×wrinkled. The F2 Generation. Some plant breeders might have stopped the experi- ments after a single cross had determined dominant and recessive characteris- tics. The results were clear cut. The F1 plants were always like one of the par- ents. Mendel, however, continued his crosses and was careful to realize that although an F1 of the round×wrinkled might be identical with the round par- ent, its parentage was different. Perhaps its offspring would reflect the differ- ent origin. Since peas are self-fertilizing, the F1 plants pollinated their own ovules and gave the F2, and when Mendel studied the F2 plants he found that both domi- nant and recessive characters were present. Now he did a 

HEREDITY AND DEVELOPMENT: SECOND EDITION 52 simple though revolutionary thing: he counted the number of individuals of each type. In every cross there was a ratio of 3 dominant to 1 recessive. His results can be summarized as follows: P F1 F2 COUNTS RATIO round×wrinkled round 5,474 round 1,850 wrinkled 2.96:1 yellow×green yellow 6,022 yellow 2,001 green 3.01:1 colored×white colored 705 colored 224 white 3.15:1 inflated×wrin- inflated 882 inflated kled 299 wrinkled 2.95:1 green pods×yel- green 428 green low pods 152 yellow 2.82:1 axial×terminal axial 651 axial 207 terminal 3.14:1 long×short long 787 long 277 short 2.84:1 These results would suggest that the rules of inheritance were the same, irrespective of the varieties being crossed. The F1 plants were always of one type, which resembled one of the parents. In the F2, two classes appeared and the frequency was 75 per cent dominants and 25 per cent recessives, or a ratio of 3:1. The F3 Generation. Mendel continued his experiments and obtained an F3 generation. We may take as an example the round×wrinkled cross, which in the F2 gave 75 per cent round and 25 per cent wrinkled. He allowed a number of the wrinkled plants to self-fertilize to give an F3, and found that all bred true, that is, only wrinkled plants were obtained in the F3. The F2 round plants gave two results: 1. One-third (193 of 565 plants) bred true, giving round plants in the F3. 2. Two-thirds (372 of 565 plants) gave round and wrinkled in a ratio of 3:1. On the basis of their genetic behavior these were like the F1 plants. Mendel’s Hypothesis. Mendel explained these results in this way: Let us assume that the round variety is round because it has a gene R, and the wrin- kled variety is wrinkled because it has gene r. (Mendel did not use the term gene but spoke of ‘factors’ or ‘traits.’ It will be simpler for us to use the mod- ern term gene from the very beginning and note the gradual change in its meaning. For the present we shall understand a gene to be the basis of an inherited character. We will not commit our- 

HEREDITY AND DEVELOPMENT: SECOND EDITION 53 selves further to what it is or where it is.) If a cross is made between the round and wrinkled varieties, the gametes of the round plant will have R and the gametes of the wrinkled plant will have r. Fertilization will produce an F1 with both genes, Rr. In appearance this plant is round, R being dominant and r recessive. We speak of the appearance of the individual as its phenotype and the genetic composition of the individual as its genotype. Thus, the phe- notype of this F1 plant is round and its genotype is Rr. Plants of the Rr type will produce gametes and Mendel assumed that any single gamete would contain either R or r but never both. He also assumed that gametes contain- ing R and gametes containing r are produced in equal numbers. If the union of F1 gametes is at random, then we will obtain a 3:1 ratio of round to wrin- kled. The entire cross could be presented in this schematic manner: It is actually unnecessary to show two plants in the F1 since both are the same. Two are used in order to make it easier to visualize the cross that gives the F2. This scheme provides a formal explanation of the results, namely, the ori- gin of the 3:1 ratio. It also shows that the F2 round plants are of two types. One in three of the round plants is pure round. If self-fertilized, it would breed true. The remaining 2/3 of the round plants are Rr. If these are allowed to self-fertilize there will result an F3 ratio of 3 round to 1 wrinkled. It will be recalled that Mendel made these tests of the F2 and the theoretical and actual results are the same. This schematic interpretation applies to all of Mendel’s crosses involving one pair of genes. Several important conclusions can be reached if the inter- pretation is correct: 1. Dominant and recessive genes do not affect one another. In the F1 of the cross discussed, the genotype was Rr. There was no visible 

HEREDITY AND DEVELOPMENT: SECOND EDITION 54 effect of the r gene, the seeds being just as round as in the pure round parent. When the Rr plant was allowed to self-fertilize both round and wrinkled seeds were obtained. These F2 wrinkled seeds were identical in appearance to the P generation wrinkled seeds. 2. The gametes produced by an F1 plant of the Rr constitution will contain either R or r, never both. 3. The R and r types of gametes will be produced in equal numbers by an Rr plant. 4. Combination between gametes is a chance affair, and the frequency of different classes of offspring will depend on the frequencies of gametes. Since an F1 plant having the Rr constitution will produce 50 per cent gametes of the R type and 50 per cent gametes of the r type, the mathe- matical basis of the F2 frequencies will be as follows: Crosses Involving Two Pairs of Genes. Mendel’s next step was to see if the conceptual scheme devised for crosses involving one pair of genes could be applied to crosses involving two pairs of genes. For this he used round and wrinkled as one pair and yellow and green as the other. Previous work had shown that the cross between yellow and green produced yellow in the F1 and a ratio of 3 yellow to 1 green in the F2. When a cross was made between a plant with round-yellow seeds and a plant with wrinkled-green seeds all of the F1 plants had round-yellow seeds. In the F2 the following seed types were obtained: 315 round-yellow 108 round-green 101 wrinkled-yellow 32 wrinkled-green One interesting thing brought out by these data is the appearance of two new seed types that were not present in either the P or the F1 generation. These new types are round-green and wrinkled-yellow. This and the other results, however, fit perfectly into the Mendelian scheme, if we assume the complete independence in inheritance of the two pairs of genes. The cross would be as follows: 

HEREDITY AND DEVELOPMENT: SECOND EDITION 55 In the formation of gametes by the F1 plant, Mendel assumed that a gamete would have only one member of a pair of genes. Thus, a gamete would have either R or r and in addition either Y or y. Four classes of gametes would be produced and these in equal frequency. The classes would be RY, Ry, rY, and ry. If an F1 plant is allowed to self-fertilize there will be these four types of pollen and the same four types of ovules. This will give 16 possible combi- nations, as shown below: Of the 16 possible F2 combinations, 9 will be round-yellow, 3 will be round-green, 3 will be wrinkled-yellow, and 1 will be wrinkled-green. Here is a comparison of Mendel’s data with the theoretical expectation: ACTUAL EXPECTED Round-yellow 315 313 Round-green 108 104 Wrinkled-yellow 101 104 Wrinkled-green 32 35 556 556 The figures given in the ‘actual’ column are those obtained by counting the seeds. The ‘expected’ values are computed in this manner: If we 

HEREDITY AND DEVELOPMENT: SECOND EDITION 56 have a total of 556 plants and expect 1/16 of them to be wrinkled-green, we find 1/16 of 556, which is 35. The other expected classes are 9/16, 3/16, and 3/16 of 556. Testing the Hypothesis. Mendel made a further test of the adequacy of his hypothesis. He predicted that the F2 plants would have four phenotypic classes and a total of nine genotypic classes (refer to the checkerboard). Genetic tests would allow him to distinguish among plants of the same pheno- type but of different genotypes. His test consisted of allowing all the F2 plants to self-fertilize to produce an F3 and then seeing if the actual results of the crosses were the same as were expected on the basis of the hypothesis. This is what he found. The Breeding Behavior of the F2 Round-yellow. It can be seen from the checkerboard that 9/16 of the F2 plants are round-yellow. These plants are listed in the first column of the table that follows, grouped accord- ing to genotype. These plants are all of the same phenotype but they belong to four different genotypes, namely RRYY, RRYy, RrYY, and RrYy. Although of identical appearance, these four genotypes should be distin- guishable on the basis of the ratios of the types of offspring they will produce following self-fertilization. These predicted ratios are listed in the third col- umn. The fourth column gives the number of plants that one would expect to give the ratio listed in column 3, if Mendel’s hypothesis is correct. For exam- ple, Mendel predicted one out of every nine round-yellow plants to be RRYY. If a plant of this genotype is self-fertilized, it would give only round- yellow offspring in the F3. No other genotype will give this result. Mendel planted 315 of the F2 round-yellow plants and of these 301 gave progeny. He would predict therefore 1/9 of these 301 plants, or 33, to be RRYY and give only round-yellow seeds. The fifth column gives the actual results. In the example we have been using, Mendel predicted that 33 of the plants would be RRYY and he found that 38 were of this genotype. F2 FRE- EXPECTED NUMBER ACTUAL QUENCY F3 RATIOS EXPECTED NUMBER RRYY 1/9 all round- 33 38 yellow RRYy 2/9 3 round- 67 65 RRYy yellow; 1 round-green RrYY 2/9 3 round- 67 60 RrYY yellow; 1 wrinkled- yellow RrYy 4/9 9 round- 134 138 RrYy yellow; 3 RrYy round-green; RrYy 3 wrinkled- yellow; 1 wrinkled- green 301 301 

HEREDITY AND DEVELOPMENT: SECOND EDITION 57 The Breeding Behavior of the F2 Round-green. Three-sixteenths of the F2 were of this category. Mendel raised 102 of these plants and these are the results: F2 FRE- EXPECTED NUMBER ACTUAL QUENCY F3 RATIOS EXPECTED NUMBER RRyy 1/3 all round- 34 35 green Rryy 2/3 3 round- 68 67 Rryy green; 1 wrinkled- green 102 102 The Breeding Behavior of the F2 Wrinkled-yellow. The wrinkled-yellow comprised 3/16 of the F2. Mendel raised 96 of these plants and these are the results: F2 FRE- NUMBER ACTUAL QUENCY EXPECTED NUMBER rrYY 1/3 all wrinkled- 32 28 yellow rrYy 2/3 3 wrinkled- 64 68 rrYy yellow; 1 wrinkled- green 96 96 The Breeding Behavior of the F2 Wrinkled-green. This category comprised 1/16 of the F2. Mendel raised 30 plants of this type. The results were as follows: F2 FREQUENCY EXPECTED F3 NUMBER ACTUAL RATIOS EXPECTED NUMBER rryy 1 all wrinkled- 30 30 green The fact that the F2 plants gave an F3 that did not differ materially from the prediction, indicated that Mendel’s conceptual scheme of inheritance was in full accord with his experimental results. In every case the actual values are surprisingly close to those expected. The expected values are based on the probability of the various types of gametes combining in a certain way. The expected and actual values are rarely identical: we should not expect them to be so any more than we should always expect five heads for every ten tosses of a coin. Mendel went one step farther and crossed plants differing in three contrast- ing characters. The results were entirely according to expectation but they will not be discussed. These are some of the conclusions that may be drawn from Mendel’s experiments: 

HEREDITY AND DEVELOPMENT: SECOND EDITION 58 1. The most important conclusion is that inheritance appears to follow def- inite and rather simple rules. Mendel was able to apply the same type of explanation to the results of all of his crosses. He had reached that stage in the development of a scientific theory where results could be pre- dicted with a high degree of accuracy. This is one goal of a scientist. 2. When plants of two different types were crossed, there was no blending of the individual characteristics. Mendel studied seven pairs of contrast- ing characters. One member of each pair of contrasting characters could be thought of as dominant and the other as recessive. In a hybrid formed from crossing a pure-breeding dominant and a pure-breeding recessive, the appearance of the plant was identical with that of the dominant parent. 3. The factors responsible for the dominant and recessive condition were not modified by their occurrence together in a hybrid. If two hybrids were crossed, both dominant and recessive offspring would appear. Nei- ther the dominant nor the recessive offspring would give any evidence of contamination resulting from hybridization. In short, an F2 recessive would be identical in genotype and phenotype to the P generation recessive. 4. When a pure-breeding plant exhibiting a dominant characteristic (A) is crossed with a recessive (a) the F1 (Aa) is like the A plant in appearance. Segregation occurs in the F2, which results in a ratio of three plants hav- ing the dominant character (one of which will be pure breeding and the other two like the F1) to one recessive. Segregation is often called Mendel’s First Law. 5. If two pairs of genes, such as Aa and Bb, are involved in a cross, each pair acts independently so far as transmission to the next generation is concerned. This phenomenon is known as independent assortment and it is often spoken of as Mendel’s Second Law. Its mode of operation can be understood if we consider the F2 originating from an F1 AaBb plant. So far as the phenotypes are concerned 3/4 of the F2 will have the A phe- notype and 1/4 will have the a phenotype. The same is true for the other pair of genes: 3/4 of the plants will have the B phenotype and 1/4 will have the b phenotype. It is entirely a matter of chance which combina- tion of genes a given F2 plant will receive. Thus of the 3/4 that will have the A phenotype, 3/4 will also have the B phenotype and 1/4 will have the b phenotype. Of the 1/4 that will have the a phenotype, 3/4 will have the B phenotype and 1/4 will have the b phenotype. So far as both char- acters are concerned 9/16 of the F2 (3/4 of 3/4) will have both the A and B phenotypes, 3/16 will have the A and b phenotypes, 3/16 will 

HEREDITY AND DEVELOPMENT: SECOND EDITION 59 have the a and B phenotypes, and 1/16 will have the a and b phenotypes. The 9:3:3:1 ratio of the F2 is due to the independent assortment of genes in the gametes of the F1 plant. 6. The gametes will contain only one type of inherited factor of each con- trasting pair. Thus the gametes of an F1 Aa plant will produce gametes containing either A or a, never both. If two factors are involved, as in an AaBb plant the gametes will be AB, or Ab, or aB, or ab, never Aa, Bb, ABb, Aab, and so on. All possible combinations will be obtained, con- sisting of one member of each pair of genes. Every type of gamete will be produced in equal frequency. It must be remembered that, without further work, these conclusions could apply only to the seven pairs of pea genes actually studied by Mendel. The fact that Mendel’s rules applied to these would indicate that other genes of peas might behave in a similar way. The discovery that rules of inheritance could be established for peas would suggest that the same or similar rules might also apply to other plants (and possibly animals). This, of course, would have to be tested by experimentation. The great worth of Mendel’s theory was that its clear and definite formulation made testing by experimen- tation possible. The same could not be said for any previous theory of inheritance. Most of the important discoveries in biology turn out in retrospect to be fairly simple. Inevitably we wonder, Why did not that idea occur to someone before? Why had no one discovered these simple relations when varieties were crossed? Why had no one realized the significance of Mendel’s approach during the 34 years between 1866 and 1900? These are unanswer- able questions, but the following facts are germane to the last one. Mendel was almost unknown among biologists during his day and his results were published in a journal that attracted little attention. This is clearly only part of the story. It is perhaps more correct to say that biologists in 1866 were unable to appreciate the significance of Mendel’s work. Their minds were not pre- pared. There is one interesting bit of information in this connection. Mendel carried on a lengthy correspondence with Nägeli, explaining the results of his experiments. It should be remembered that Nägeli was greatly interested in heredity, he being the proponent of the idioplasm concept. He, of all people, should have seen Mendel’s point but he failed to appreciate the significance of the pea experiments. Still another fact is that Mendel did not believe for long in the universality of his findings. This was the result of an unfortunate choice of material, the hawkweed, which was recommended to him by Nägeli for 

HEREDITY AND DEVELOPMENT: SECOND EDITION 60 some additional experiments. In the hawkweed the ovules are capable of parthenogenetic development. As a result, many of the crosses he believed he was performing were not crosses at all. Mendel did not realize this and was unable to understand why he did not observe the ratios he had previously found in peas. He probably came to believe that his results held for peas alone. Mendel and his ideas were of no importance during the last third of the nineteenth century when students of inheritance concerned themselves mainly with the cycle of chromosomal behavior in meiosis, fertilization, and the mitotic divisions during development. In the last few years before 1900, the three scientists who were to redis- cover Mendel’s work were experimenting with crosses of varieties of plants. Two of them, Hugo de Vries (1848–1935) and Carl Correns (1864–1935), independently discovered Mendel’s rules of inheritance before they knew of Mendel. In 1900, de Vries reported the results of hybridizing varieties of 15 species of plants. When one member of the parental generation was dominant and the other recessive, the F1 generation always resembled the dominant parent. In the F2 generations, he observed the 3:1 ratio that Mendel had found long before: the number of recessives in the 15 crosses varied from 22 to 28 per cent, averaging 24.93 per cent. De Vries emphasized the critical point that, in the F1 individuals which have dominant and recessive genes, the gametes are pure, that is, they have only one sort of gene, never both. This phenomenon, the Purity of the Gametes, was to be a matter of contention for years. What could the mechanism possibly be? It was difficult to accept any biological phenomenon for which there seemed to be no mechanism. Carl Correns conducted extensive crosses among varieties of corn and peas and also published in 1900. In most instances he obtained the same results as had Mendel. There were exceptions, however. In a few instances there was no dominance: the F1 individuals were intermediate in appearance. Correns reported also that Mendel’s Law of Segregation did not always apply, though in the majority of cases it did. Since segregation was the usual result, however, he wondered how it might come about. Thus in an F1 hybrid, which might be symbolized Aa how could the gametes come to contain either A or a, never both? And what could account for the fact that the breed- ing results indicated that the ratio of A to a is 1:1? He made the tentative and prophetic suggestion that the chromosomes could be responsible. Thus, seg- regation could be based on the separation of chromosomes at a nuclear divi- sion, quite possibly the one in meiosis that Weismann referred to as the reduc- tion division. Clearly there was more to Mendel’s laws than peas. 

HEREDITY AND DEVELOPMENT: SECOND EDITION 61 Confirmations and Exceptions to Mendel’s Scheme. In the first few years after 1900, when Mendel’s findings became widely known to biolo- gists, the results of many crosses were reported. The majority of these gave ratios that were nearly identical with Mendel’s pea crosses. That is, in a cross of a pure-breeding dominant and a pure-breeding recessive, the F1 population consisted only of plants with the dominant characteristics. The F2 of such a cross contained both of the original types, in the ratio of three dominants to one recessive. If one of the F1 plants was crossed with a pure recessive, the ratio of dominants to recessives in the offspring was 1:1. If two pairs of con- trasting characters were involved, the F2 ratio was 9:3:3:1. If the F1 of the cross just mentioned was crossed to a double recessive, the ratio was 1:1:1:1. A few gave slightly different results that could be understood with minor adjustments of the Mendelian scheme. Still others defied explanation at that time. This last group of cases was put aside in the hope that eventually a mod- ified Mendelian theory could explain the results. Subsequent events showed this to be a profitable procedure. In these early years of the twentieth century, the British geneticist, William Bateson (1861–1926), was the most vigorous disciple of Mendelism. Even before Mendel’s work was known to the scientific world at large, Bateson had undertaken an extensive program of breeding. As a result of this prepara- tion, he was in a proper frame of mind to grasp the significance of Mendel’s work. In England, Bateson waged a scientific battle to convince his fellow biologists that Mendel’s approach to the problem of inheritance was a useful one. This ‘battle’ was not always waged with the fairness, objectivity, lack of bias, and honest criticism that should be the basis for scientific discussions. In fact, the participants behaved like ordinary human beings. Much of the genetic work of this period was summarized in reports Bateson made to the Royal Society (1902, 1905, 1906, 1908, 1909) and in his book, Mendel’s Principles of Heredity (1909). Some Useful Genetic Terms. Bateson and others introduced some terms that are useful in describing genetic events. From Mendel’s experiments he ‘reached the conception of unit-characters existing in antagonistic pairs. Such characters we propose to call allelomorphs [now called alleles], and the zygote formed by the union of a pair of opposite allelomorphic gametes, we shall call a heterozygote. Similarly, the zygote formed by the union of gametes having similar allelomorphs, may be spoken of as a homozygote.’ To use these terms in examples, we might observe that in peas round and wrinkled genes are alleles; so are yellow and green genes. A pure- 

HEREDITY AND DEVELOPMENT: SECOND EDITION 62 3–1 Combs of fowls. a. single. b. rose. c. pea. d. walnut. (From T.H.Morgan. 1919. “The Physical Basis of Inheritance.” Lippincott.) breeding round plant, which we have designated RR,* is homozygous. A wrinkled plant, rr, is also homozygous. The F1 of a cross of these is Rr and heterozygous. Recalling that round is dominant, we know that a round plant can be either homozygous (RR) or heterozygous (Rr), and that one could not tell by external appearance which was which. It is worth repeating that there is a difference between appearance and genetic make-up. We speak of the appearance of the organism as its phenotype (yellow or green) and the genetic make-up as its genotype (RR, Rr, or rr). The individual factors of inheri- tance, R or r, carried on the chromosomes are the genes. * Heretofore we have been following Mendel’s method of notation and used R, rather than RR. In 1900 both would have meant the same. Other studies, being car- ried out in the early 1900s, suggested that RR is a more accurate way of designat- ing a pure-breeding dominant individual. The reasons will be given in the next chapter. 

HEREDITY AND DEVELOPMENT: SECOND EDITION 63 Returning now to Bateson, these are some of the types of genetic data he gave: EXCEPTIONS TO THE MENDELIAN RATIOS 1. Blended Character Expression in Heterozygotes. In Mendel’s results the heterozygote was always identical in appearance with the homozygous dominant. Even today we recognize this as the most frequent condition, but there are some cases where the heterozygote is intermediate. In such a situa- tion neither allele is dominant or recessive. One example is a common culti- vated flower, the four o’clock. When a red-flowered four o’clock is crossed with a white-flowered one, all of the F1 plants have pink flowers. In the F2, red-, white-, and pink-flowered plants appear. The genetic basis of this cross is diagrammed below: 2. Two Pairs of Alleles Affecting the Same Character. In all the crosses considered so far, a character has been affected by only one pair of alleles. This may seem to imply that every character of an organism is determined by a single pair of alleles. This is not the case, as shown by some experiments with chickens which were reported by Bateson. Poultry breeders recognized a number of comb types, usually involving differences in comb shape. Some of these types were called single, rose, pea, and walnut (Fig. 3–1). A cross between rose and single gave 

HEREDITY AND DEVELOPMENT: SECOND EDITION 64 rose in the F1 and 3 rose to 1 single in the F2. Rose and single behaved as ordinary alleles with rose the dominant. Similarly, a cross between pea and single gave pea in the F1 and 3 pea to 1 single in the F2. Pea and single behaved as ordinary alleles with pea the dominant. Considered separately there is nothing unusual about these crosses. Con- sidered together there is one puzzle, largely semantic: why is the genotype of single written as rr in the first cross and as pp in the second? The answer to this question hinges on the fact that the single comb condition results from the interaction of two different genes. The two 

HEREDITY AND DEVELOPMENT: SECOND EDITION 65 previous crosses and the next one to be described show that both the r and p genes are involved in the genetic determination of comb shape (subsequent experiments showed that additional genes were concerned). A comb of the single type forms in a chicken when both the pea and rose genes are reces- sive. The genotype of a single comb chicken, therefore, is pprr. A pea comb chicken would have the genotype PPrr or Pprr and a rose comb chicken would have the genotype ppRR or ppRr. We might have written the cross of rose comb×single comb as ppRR ×pprr. At that time, however, we were unaware of the existence of the p genes. Furthermore, there was no need to do so since both parents are of the same genotype with respect to the p gene: by convention geneticists use the symbols only for those cases where the genes differ in the two parents. If the cross involves differences in both the p and r comb shape genes, then the necessary genetic symbols must be employed. Such a cross will now be described. Let us cross the two dominants, rose and pea. The F1 will be found to have a new type of comb, walnut, which might be looked upon as a blending of the two dominant shapes. The F2 will give a ratio of 9 walnut, 3 rose, 3 pea, and 1 single. 

HEREDITY AND DEVELOPMENT: SECOND EDITION 66 The single comb is the result of both (recessive) p and r genes being homozygous. Rose is obtained if the animal is homozygous or heterozygous for R and homozygous for p. Pea is obtained if the animal is homozygous or heterozygous for P and homozygous for r. Walnut results when there is at least one P gene together with at least one R gene. 3. Yellow Mice. Cuénot reported some crosses in mice that neither he nor Bateson could explain in the usual Mendelian manner. He worked with yel- low and agouti hair color genes. These two types of crosses will demonstrate the problem. 1. yellow×yellow gives 2 yellow to 1 agouti. 2. yellow×agouti gives 1 yellow to 1 agouti. Cuénot found it impossible to obtain a strain of yellow mice that would breed true. The yellow animals always behaved as though they were heterozygous. His agouti strains bred true. During the course of his experiments he observed that the litter size in crosses of yellow× yellow was smaller than in the yellow×agouti cross. Can you devise a hypothesis to explain the results? From the data given it is possible to arrive at the explanation that was later found to be correct. 4. Coupling of Genes. Bateson listed another discovery that could not be explained, namely, cases involving two pairs of genes that did not show inde- pendent assortment. Let us assume that there are two pairs of genes, A and a and B and b and that the phenotypic expression of A is A, that of a is a, and so on. In the cross AABB×aabb we should expect an F2 phenotypic ratio of 9 AB, 3 Ab, 3 aB, and 1 ab if Mendel’s rules applied. In some crosses, however, Bateson found that the A and B characters appeared to be completely cou- pled, that is, they were inherited together. The same was true for a and b. In fact, the F2 ratios might be close to 3 AB to 1 ab with few or no individuals of the Ab or aB phenotypes. Results of this sort could not be accounted for by the Mendelian scheme. Limitations of Mendelism. A biologist who restricted himself solely to a Mendelian approach, that is, to a study of the inheritance of ‘unit characters’ as expressed in the ratios observed in succeeding generations, could make considerable progress. He could study numerous sorts of animals and plants and observe the instances where Mendel’s rules held and when they did not. Many individuals restricted their investigations in this way: Bateson and his coworkers were among them. But one soon realizes that the prospects for a deeper understanding of inheritance are limited. 

HEREDITY AND DEVELOPMENT: SECOND EDITION 67 Mendelism really bothered many biologists: it seemed so at variance with the phenomena they usually observed. They knew of few instances that exhib- ited the extraordinary mathematical exactness that one could easily observe in Mendelian crosses. Furthermore, biologists seek to identify the physical (i. e. structural) basis of phenomena. What in the organism and its gametes could be responsible for Mendelian inheritance? Could it be gemmules or an idioplasm behaving in some exact manner? How could one possibly account for the ‘purity of the gametes,’ that is, for an Rr individual to produce either R or r gametes but never Rr gametes—and to produce them in such exact ratios? The answers lay elsewhere. Suggested Readings Chapter 3 of Readings contains long excerpts from the report that Bateson made to the Royal Society in 1902, in which he gave a detailed account of Mendel’s experiments and adds much new data. A paper by T.H.Morgan, questioning the basic tenets of Mendelism, is also reproduced. DUNN, L.C. 1965. A Short History of Genetics. New York: McGraw-Hill. MENDEL, GREGOR. 1866. ‘Experiments on plant hybrids.’ (See Stern and Sherwood) OLBY, ROBERT C. 1966. Origins of Mendelism. New York: Schocken Books. STERN, CURT, and EVA R.SHERWOOD. Editors. 1966. The Origins of Genetics. A Mendel Source Book. San Francisco: W.H.Freeman. Translations of papers by Mendel, de Vries, and Correns; Mendel’s letters to Nägeli; Fisher’s attack on Mendel and Wright’s reply ; and references to Mendel’s experiments in Focke’s monograph on plant hybrids. STURTEVANT, A.H. 1965. A History of Genetics. New York: Harper and Row. Questions 1. Four desirable features for experimentation are listed for Mendel’s peas. Why is each desirable? 2. In a plant of the genotype Rr Yy, Mendel assumed that the gametes could only be RY, Ry, rY, and ry. According to his scheme, Rr Yy, Rr Y, Rr, and Yy could not be formed. What is the basis of his belief that such gametes could not be formed? Can you devise a mechanism that would allow some types of gametes to form (i.e. RY, Ry etc.) but not others (i.e. Yy, Rr)? (If you already know what the solution eventually proved to be, ignore it, and try to devise other mechanisms.) 3. Account for the fact that pre-Mendelian hybridizers found blending to be a rule of inheritance but that Mendel did not. 4. What do the phenomena of dominance-recessiveness, segregation, and independent assortment tell us about the Mendelian units of inheritance? 

HEREDITY AND DEVELOPMENT: SECOND EDITION 68 5. How do you suppose Aristotle (Readings, Chapter 1) would have reacted to Mendel’s experiments? 6. A pea plant that is yellow and round is crossed with one that is green and wrinkled. The offspring are: 1/2 yellow, round 1/2 green, round What was the genotype of the parents? 7. In another cross of peas the offspring are: 3/8 yellow, round 3/8 yellow, wrinkled 1/8 green, round 1/8 green, wrinkled What was the genotype and the phenotype of the parents? Hint. When doing genetic problems of this type, it is best to solve for one character at a time. It is necessary, also, to remember how the usual genetic ratios are obtained. Thus, a 3:1 ratio is the consequence of cross- ing two heterozygotes, Aa×Aa. A 1:1 ratio is the consequence of cross- ing a heterozygote and a homozygous recessive, Aa×aa. 8. In man brown eyes (B) is dominant over blue (b). (The genetic situation is not quite this simple but, in doing the following problems, assume that it is.) a. A heterozygous brown-eyed woman marries a blue-eyed man. What will be the genotypes and phenotypes of the children? b. The first child of two brown-eyed parents has blue eyes. What are the genotypes of the three individuals? What other genotypes, and in what proportion, might be expected in future children of these parents? c. In a family of nine children two have blue eyes and seven have brown eyes. What are the probable genotypes and phenotypes of the parents? 9. How might Mendel have accounted for the pattern of inheritance described by Darwin for color blindness (pages 12, 15)? For the porcu- pine man (page 9)? 10. What evidence can be cited to show that two alleles are not modified by their occurrence together in a heterozygous individual? 11. Can you modify Darwin’s Theory of Pangenesis in such a way that it will account for the results obtained by Mendel? 12. Before Mendel’s work was rediscovered in 1900, many biologists held the hypothesis that the nucleus was responsible for inheritance. Do Mendel’s results support this hypothesis? 13. A walnut rooster, heterozygous for both rose and pea, is crossed with a hen having a single comb. What will be the genotypes and phenotypes of the offspring? 

HEREDITY AND DEVELOPMENT: SECOND EDITION 69 14. A walnut rooster is crossed with a rose hen. The offspring are: 3/4 walnut 1/4 pea What were the genotypes of the parents? 15. Did you formulate a reasonable hypothesis to account for inheritance in yellow mice? 16. A Mendelian cross of the type Aa×aa gives a 1:1 ratio. In man, and most other animals, the ratio of females to males is also 1:1. Evaluate this hypothesis: The inheritance of sex is an example of a simple Mendelian cross.