Read Ebook: Sex-linked Inheritance in Drosophila by Bridges Calvin B Calvin Blackman Morgan Thomas Hunt

Font size: 10 px 15 px 20 px 25 px 30 px 35 px

Background color: BlackWhiteGrayLight GrayDark GrayDim Gray

Text color: BlackWhiteGrayLight GrayDark GrayDim Gray

Apply/Save settings

Ebook has 280 lines and 81716 words, and 6 pages

PAGE.

Mendel's law of segregation 5 Linkage and chromosomes 5

Crossing-over 7

The Y chromosome and non-disjunction 8

MENDEL'S LAW OF SEGREGATION.

LINKAGE AND CHROMOSOMES.

The sons get their single X chromosome from their mother, and should therefore show any character whose gen is carried by such a chromosome. In sex-linked inheritance all sons show the characters of their mother. A male transmits his sex-linked character to his daughters, who show it if dominant and conceal it if recessive. But any daughter will transmit such a character, whether dominant or recessive, to half of her sons. The path of transmission of the gen is the same as the path followed by the X chromosome, received here from the male. Many other combinations show the same relations. In the case of non-disjunction, to be given later, there is direct experimental evidence of such a nature that there can no longer be any doubt that the X chromosomes are the carriers of certain gens that we speak of as sex-linked. This term is intended to mean that such characters are carried by the X chromosome. It has been objected that this use of the term implies a knowledge of a factor for sex in the X chromosome to which the other factors in that chromosome are linked; but in fact we have as much knowledge in regard to the occurrence of a sex factor or sex factors in the X chromosome as we have for other factors. It is true we do not know whether there is more than one sex-factor, because there is no crossing-over in the male , and crossing-over in the female does not influence the distribution of sex, since like parts are simply interchanged. It follows from this that we are unable as yet to locate the sex factor or factors in the X chromosome. The fact that we can not detect crossing-over under this condition is not an argument against the occurrence of linkage. We are justified, therefore, in speaking of the factors carried by the X chromosome as sex-linked.

CROSSING-OVER.

While the genetic evidence forces one to accept crossing-over between the sex chromosomes in the female, that evidence gives no clue as to how such a process is brought about. There are, however, certain facts familiar to the cytologist that furnish a clue as to how such an interchange might take place. When the homologous chromosomes come together at synapsis it has been demonstrated, in some forms at least, that they twist about each other so that one chromosome comes to lie now on the one side now on the other of its partner. If at some points the chromosomes break and the pieces on the same side unite and pass to the same pole of the karyokinetic spindle, the necessary condition for crossing-over will have been fulfilled.

THE Y CHROMOSOME AND NON-DISJUNCTION.

Ordinarily all the sons and none of the daughters show the recessive sex-linked characters of the mother when the father carries the dominant allelomorph. The peculiarity of non-disjunction is that sometimes a female produces a daughter like herself or a son like the father, although the rest of the offspring are perfectly regular. For example, a vermilion female mated to a wild male produces vermilion sons and wild-type daughters, but rarely also a vermilion daughter or a wild-type son. The production of these exceptions by a normal XX female must be due to an aberrant reduction division at which the two X chromosomes fail to disjoin from each other. In consequence both remain in the egg or both pass into the polar body. In the latter case an egg without an X chromosome is produced. Such an egg fertilized by an X sperm produces a male with the constitution XO. These males received their single X from their father and therefore show the father's characters. While these XO males are exceptions to sex-linked inheritance, the characters that they do show are perfectly normal, that is, the miniature or the bar or other sex-linked characters that the XO male has are like those of an XY male, showing that the Y normally has no effect upon the development of these characters. But that the Y does play some positive r?le is proved by the fact that all the XO males have been found to be absolutely sterile.

The evidence is equally positive that sex is quantitatively determined by the X chromosome--that two X's determine a female and one a male. For in the case of non-disjunction, a zero or a Y egg fertilized by an X sperm produces a male, while conversely an XX egg fertilized by a Y sperm produces a female. It is thus impossible to assume that the X sperms are normally female-producing because of something else than the X or that the Y sperm produce males for any other reason than that they normally fertilize X eggs. Both the X and the Y sperm have been shown to produce the sex opposite to that which they normally produce when they fertilize eggs that are normal in every respect, except that of their X chromosome content. These facts establish experimentally that sex is determined by the combinations of the X chromosomes, and that the male and female combinations are the causes of sex differentiation and are not simply the results of maleness and femaleness already determined by some other agent.

Cytological examination has demonstrated the existence of one XXYY female, and has checked up the occurrence in the proper classes and proportions of the XXY females. Numerous and extensive breeding-tests have been made upon the other points discussed. The evidence leaves no escape from the conclusion that the genetic exceptions are produced as a consequence of the exceptional distribution of the X chromosomes and that the gens for the sex-linked characters are carried by those chromosomes.

MUTATION IN DROSOPHILA AMPELOPHILA.

MULTIPLE ALLELOMORPHS.

It appears that Cu?not was the first to find a case in which the results could be explained on the basis that more than two factors may stand in the relation of allelomorphs to each other. In other words, a given factor may become the partner of more than one other factor, although, in any one individual, no more than two factors stand in this relation. While it appears that his evidence as published was not demonstrative, and that, at the time he wrote, the possibility of such results being due to very close linkage could not have been appreciated as an alternative explanation, nevertheless it remains that Cu?not was right in his interpretation of his results and that the factors for yellow, gray, gray white-belly, and black in mice form a system of quadruple allelomorphs.

The other system of multiple allelomorphs in the first chromosome is a triple system made up of yellow , spot , and their normal allelomorph--the factor in the normal fly that stands for "gray."

In general it may be said that there are two principal ways in which it is possible to show that certain factors are the allelomorphs of each other. First, if they are allelomorphs only two can exist in the same individual; and, in the case of sex-linked characters, while two may exist in the same female, only one can exist in the male, for he contains but one X chromosome. Second, all the allelomorphs should give the same percentages of crossing-over with each other factor in the same chromosome.

The factors in the first chromosome are linked to each other in various degrees. When they are as closely linked as yellow body-color and white eyes crossing-over takes place only once in a hundred times. If two factors were still nearer together it is thinkable that crossing-over might be such a rare occurrence that it would require an enormous number of individuals to demonstrate its occurrence. In such a case the factors might be said to be completely linked, yet each would be supposed to have its normal allelomorph in the homologous chromosome of the wild type. Imagine, then, a situation in which one of these two mutant factors enters from one parent and the other mutant factor from the other parent. The normal allelomorph of a may be called A. It enters the combination with b, while the normal allelomorph B of b enters the combination with a. Since b is completely linked to A and a to B, the result will be the same as though a and b were the allelomorphs of each other, for in the germ-cells of the hybrid aBAb the assortment will be into aB and Ab, which is the same as though a and b acted as segregating allelomorphs.

One of the most striking facts connected with the subject of multiple allelomorphs is that the same kind of change is effected in the same organ. Thus, in the quadruple system mentioned above, the color of the eye is affected. In the yellow-spot system the color of the body is involved. In mice it is the coat-color that is different in each member of the series. While this is undoubtedly a striking relation and one which seems to fit well with the idea that such effects are due to mutative changes in the same fundamental element that affects the character in question, yet on the other hand it would be dangerous to lay too much emphasis on this point, because any given organ may be affected by other factors in a similar manner, and also because a factor frequently produces more than a single effect. For instance, the factor that when present gives a white eye affects also the general yellowish pigment of the body. If red-eyed and white-eyed flies are put for several hours into alcohol, the yellowish body-color of the white-eyed flies is freely extracted, but not that of the red-eyed flies. In the living condition the difference between the body-colors of the red- and of the white-eyed flies is too slight to be visible, but after extraction in alcohol the difference is striking. There are other effects also that follow in the wake of the white factor. Now, it is quite conceivable that in some specific case one of the effects might be more striking than the one produced in that organ more markedly affected by the other factor of the allelomorphic series. In such a case the relation mentioned above might seemingly disappear. For this reason it is well not to insist too strongly on the idea that multiple allelomorphs affect the same part in the same way, even although at present that appears to be the rule for all known cases.

SEX-LINKED LETHALS AND THE SEX RATIO.

There are some general relations that concern the lethals that may be mentioned here, while the details are left for the special part or are found in the special papers dealing with these lethals. A factor of this kind carried by the X chromosome would be transmitted in the female line because the female, having two X chromosomes, would have one of them with the normal allelomorph of the lethal factor carried by the other X chromosome. Half of her sons would get one of her X's, the other half the other. Those sons that get the lethal X will die, since the male having only one X lacks the power of containing both the lethal and its normal allelomorph. The other half of the sons will survive, but will not transmit the lethal factor. In all lethal stocks there are only half as many sons as daughters. The heterozygous lethal-bearing female, fertilized by a normal male, will give rise to two kinds of daughters; one normal in both X's, the other with a normal X and a lethal-bearing X chromosome. The former are always normal in behavior, and the latter repeat in their descendants the 2:1 sex-ratio.

Whether a female bearing the same lethal twice would die, can not be stated, for no such females are obtainable, because the lethal males, which alone could bring about such a condition, do not exist. The presumption is that a female of this kind would also die if the lethal acts injuriously on some vital function or structure.

Since only half of the daughters of the lethal-bearing females carry the lethal, the stock can be maintained by breeding daughters separately in each generation to insure obtaining one which repeats the 2:1 ratio. There is, however, a much more advantageous way of carrying on the stock--one that also confirms the sufficiency of the theory.

In carrying on a stock of a lethal, advantage can be taken of linkage. A lethal factor has a definite locus in the chromosome; if, then, a lethal-bearing female is crossed to a male of another stock with a recessive character whose factor lies in the X chromosome very close to the lethal factor, half the daughters will have lethal in one X and the recessive in the other. The lethal-bearing females can be picked out from their sisters by the fact that they give a 2:1 sex-ratio, and by the fact that nearly all the sons that do survive show the recessive character. If such females are tested by breeding to the recessive males, then the daughters which do not show the recessive carry the lethal, except in the few cases of crossing-over. Thus in each generation the normal females are crossed to the recessive males with the assurance that the lethal will not be lost. If instead of the single recessive used in this fashion, a double recessive of such a sort that one recessive lies on each side of the lethal is used, then in each generation the females which show neither recessive will almost invariably contain the lethal, since a double cross-over is required to remove the lethal.

INFLUENCE OF THE ENVIRONMENT ON THE REALIZATION OF TWO SEX-LINKED CHARACTERS.

The need of a special environment in order that certain mutant characters may express themselves has been shown for abnormal abdomen and for reduplication of the legs . In a third type, club, described here , the failure of the unfolding of the wing which occurs in about 20 per cent of the flies is also without much doubt an environmental effect, but as yet the particular influence that causes the change is unknown.

A demonstration is given in this instance of the interaction between a given genotypic constitution and a special environment. The character abnormal is a sex-linked dominant. Therefore, if an abnormal male is mated to a wild female the daughters are heterozygous for abnormal, while the sons, getting their X chromosome from their mother, are entirely normal. In a wet environment all the daughters are abnormal and the sons normal. As the culture dries out the daughters' color becomes normal in appearance. But while the sons will never transmit abnormality to any of their descendants in any environment, the daughters will transmit in a suitable environment their peculiarity to half of their daughters and to half of their sons. The experiment shows convincingly that the abnormal abdomen appears in a special environment only in those flies that have a given genotypic constitution.

As the cultures dry out the abnormal males are the first to change over to normal, then the heterozygous females, and lastly the homozygous females. It is doubtful if any far-reaching conclusion can be drawn from this series, because the first and second classes differ from each other not only in the presence of one or of two factors for abnormal, but also by the absence in the first case of an entire X chromosome with its contained factors. The second and third classes differ from each other only by the abnormal factor.

Similar results were found in the mutant type called reduplicated legs, which is a sex-linked recessive character that appears best when the cultures are kept at about 10? C. As Miss M. A. Hoge has shown, this character then becomes realized in nearly all of the flies that have the proper constitution, but not in flies of normal constitution placed in the same environment. Here the effect is produced by cold.

SEXUAL POLYMORPHISM.

Outside the primary and secondary sexual differences between the male and the female, there is a considerable number of species of animals with more than one kind of female or male. Darwin and his followers have tried to explain such cases on the grounds that more than one kind of female might arise through natural selection, in consequence of some individuals mimicking a protected species. It is needless to point out here how involved and intricate such a process would be, because the mutation theory has cut the Gordian knot and given a simpler solution of the origin of such diandromorphic and digynomorphic conditions.

FERTILITY AND STERILITY IN THE MUTANTS.

Aside from the decrease in fertility that occurs in certain stocks , there are among the types described in the text two cases that call for special comment. When the mutant type called "rudimentary" was first discovered, it was found that the females were sterile but the males were fully fertile. Later work has revealed the nature of the sterility of the female. The ovaries are present and in the young flies appear normal, but while in the normal flies the eggs in the posterior portion enlarge rapidly during the first few days after hatching, in the rudimentary females only a very few eggs enlarge. The other eggs in the ovary remain at a lower stage of their development. Rarely the female lays a few eggs; when she does so some of the eggs hatch, and if she has been mated to a rudimentary male, the offspring are rudimentary females and males. The rudimentary females mate in the normal time with rudimentary or with normal males, and their sexual behavior is normal. Their sterility is therefore due to the failure of the eggs to develop properly. Whether in addition to this there is some incompatibility between the sperm and the eggs of this type is not conclusively disproved, but is not probable from the evidence now available.

In the mutant called "fused" the females are sterile both with wild males and with males from their own stock. An examination of the ovaries of these females, made by Mr. C. McEwen, shows clearly that there are fewer than the normal number of mature eggs, recalling the case of rudimentary.

It should be noticed that there is no apparent relation between the sterility of these two types and the occurrence of the mutation in the X chromosome, because other mutations in the X do not cause sterility, and there is sterility in other mutant types that are due to factors in other chromosomes.

BALANCED INVIABILITY.

The determination of the cross-over values of the factors was at first hindered because of the poor viability of some of the mutants. If the viability of each mutant type could be determined in relation to the viability of the normal, "coefficients of viability" could serve as corrections in working with the various mutant characters. But it was found that viability was so erratic that coefficients might mislead. At the same time it was becoming more apparent that poor viability is no necessary attribute of a character, but depends very largely on the condition of culture. Competition among larvae was found to be the chief factor in viability. Mass cultures almost invariably have extremely poor viability, even though an attempt is made to supply an abundance of food. Special tests showed that even those mutants which were considered the very poorest in viability were produced in proportions fairly close to the theoretical when only one female was used for each large culture bottle and the amount and quality of food was carefully adjusted.

For the majority of mutants which did well even under heavy competition in mass cultures the pair-breeding method reduced the disturbances due to viability to a point where they were negligible.

Later a method was devised whereby mutations of poor viability could be worked with in linkage experiments fairly accurately and whereby the residual inviability of the ordinary characters could be largely canceled. This method consists in balancing the data of a certain class with poor viability by means of an equivalent amount of data in which the same class occurs as the other member of the ratio. Thus in obtaining data upon any linkage case it is best to have the total number of individuals made up of approximately equal numbers derived from each of the possible ways in which the experiment may be conducted. In the simplest case, in which the results are of the form AB:Ab:aB:ab, let us suppose that the class ab has a disproportionately low viability. If, then, ab occurs in an experiment as a cross-over class, that class will be too small and a false linkage value will be calculated. The remedy is to balance the preceding data by an equal amount of data in which ab occurs as a non-cross-over. In these latter the error will be the opposite of the previous one, and by combining the two experiments the errors should be balanced to give a better approximation to the true value. When equal amounts of data, secured in these two ways, are combined, all four classes will be balanced in the required manner by occurring both as non-cross-overs and as cross-overs. The error, therefore, should be very small. For three pairs of gens there are eight classes, and in order that each of them may appear as a non-cross-over, as each single cross-over, and as the double cross-over, four experiments must be made.

HOW THE FACTORS ARE LOCATED IN THE CHROMOSOMES.

If these tests show that the new mutant does not belong to either the second or third chromosome, that is, if both with black and with pink the 9:3:3:1 ratio is obtained, then by exclusion the factor lies in the fourth chromosome, in which as yet only two factors have been found.

The list at the top of page 21 gives the names of the factors dealt with in this paper. They stand in the order of their discovery, the mutant forms reported here for the first time being starred.

In each experiment the percentage of crossing-over is found by dividing the number of the cross-overs by the sum of the non-cross-overs and the cross-overs, and multiplying this quotient by 100. The resulting percentages, or cross-over values, are used as measures of the distances between loci. Thus if the experiments give a cross-over value of 5 per cent for white and bifid, we say that white and bifid lie 5 units apart in the X chromosome. Other experiments show that yellow and white are about 1 unit apart, and that yellow and bifid are about 6 units apart. We can therefore construct a diagram with yellow as the zero, with white at 1, and with bifid at 6. If we know the cross-over values given by a new mutant with any two mutants of the same chromosome whose positions are already determined, then we can locate the new factor with accuracy, and be able to predict the cross-over value which the new factor will give with any other factor whose position is plotted.

The factors are located preferably by short distances , because when the amount of crossing-over is large a correction must be made for double crossing-over, and the correction can be best found through breaking up the long distances into short ones, by using intermediate points.

Conversely, when a long distance is indicated on the chromosome diagram, the actual cross-over value found by experiment will be less than the diagram indicates, because the diagram has been corrected for double crossing-over.

It may be asked what will happen when two factors whose loci are more than 50 units apart in the same chromosome are used in the same experiment? One might expect to get more than 50 per cent of cross-overs with such an experiment, but double crossing-over becomes disproportionately greater the longer the distance involved, so that in experiments the observed percentage of crossing-over does not rise above 50 per cent. For example, if eosin is tested against bar, somewhat under 50 per cent of cross-overs are obtained, but if the distance of bar from eosin is found by summation of the component distances the interval for eosin bar is 56 units.

In calculating the loci of the first chromosome, a system of weighting was used which allowed each case to influence the positions of the loci in proportion to the amount of the data. In this way advantage was taken of the entire mass of data.

The factors which lie close to yellow were the first to be calculated and plotted. The next step was to determine very accurately the position of vermilion with respect to yellow. There are many separate experiments which influence this calculation and all were proportionately weighted. Then, using vermilion as the fixed point the factors which lie close to vermilion were plotted. The same process was repeated in locating bar with respect to vermilion and the factors about bar with reference to bar. The last step was to interpolate the factors , which form a group about midway between yellow and vermilion. Of these, club is the only one whose location is accurate. The apparent closeness of the grouping of these loci is not to be taken as significant, for they have been placed only with reference to the distant points yellow and vermilion and not with respect to each other; furthermore, the data available in the cases of lemon and depressed are very meager.

The factors which are most important and are most accurately located are yellow, white , bifid, club, vermilion, miniature, sable, forked, and bar. Of these again, white , vermilion, and bar are of prime importance and will probably continue to claim first rank. Of the three allelomorphs, white, eosin, and cherry, eosin is the most useful.

NOMENCLATURE.

Share on: WhatsApp @Hash Facebook Tweet