Heterozygosity

“ CROSSING-OVER.
When two or more sex-linked factors are present in a male they are always transmitted together to his daughters, as must necessarily be the case if they are carried by the unpaired X chromosome. If such a male carrying, let us say, two sex-linked factors, is mated to a wild female, his daughters will have one X chromosome containing the factors for both characters, derived from the father, and another X chromosome that contains the factors that are normal for these two factors (the normal allelomorphs) . ”

“ 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 (i.e., one homozygous for a given lethal) would die, can not be stated, for no such females are obtainable, because the lethal males, which alone could bring about {15}such a condition, do not exist. ”

“ The evidence that the chromosomes are structural elements of the cell that perpetuate themselves at every division has continually grown stronger. That factors have the same distribution as the chromosomes is clearly seen in the case of sex-linked characters, where it can be shown that any character of this type appears in those individuals which from the known distribution of the X chromosomes must also contain the chromosome in question. For example, in Drosophila, as in many other insects, there are two X chromosomes in the cells of the female and one X chromosome in the cells of the male. ”

“ There is a class of cases of inheritance, due to the XY chromosomes, that is called sex linked inheritance. It is shown both by mutant characters and characters of wild species.
For instance, white eye color in Drosophila shows sex linked inheritance. If a white eyed male is mated to a wild red eyed female (fig. 35) all the offspring have red eyes. If these are inbred, there are three red to one white eyed offspring, but white eyes occur only in the males. ”

“ The visible properties developed by a zygote in the course of its growth depend upon the nature and variety of the factors carried in by the two gametes which went to its making, and to a less degree upon whether each factor was brought in by both gametes or by one only. If the given factor is brought in by one gamete only, the resulting heterozygote may be more or less intermediate between the homozygous form with a double dose of the factor and the homozygous form which is entirely destitute of the factor. Cases in point are those of the primula flowers and the Andalusian fowls. ”

“ At the same time it must be borne in mind that since the factor, whether a portion of a chromosome or not, is transmitted in heredity as a part of a single cell, the gamete, and since every cell of the developed individual is derived by division from the single zygote cell formed by the union of the two gametes, the factor or determinant must be contained in every cell of the soma, except in cases where differential division, or what is called somatic segregation, takes place. ”

“ A pure recessive individual is one arising from the union of two gametes both carrying recessives. If a heterozygote is bred with a pure recessive the offspring are half heterozygote and half recessive. The heterozygote individual in typical cases shows the dominant character. In the formation of its gametes when the reduction division of the chromosomes takes place, half of them receive the dominant character, half the recessive. When the division in the gametes of the recessive individual takes place its gametes all contain the recessive character. ”

“ Finally, the fact that these supposed vehicles of inheritance occur in equal numbers in each of the conjugating germ-cells, and that this number is always, both in animals and in plants, half of the normal number occurring in somatic cells, is decisive. The logical necessity that the hereditary substance of both parents should be transmitted to the offspring in equal quantity could not be more precisely met than it is by the fact that half the normal number of chromosomes occurs in each of the sex-nuclei in the ovum. ”

“ All perhaps would agree that it implies the existence in the germ-cell of specific determiners essential for the production of particular characteristics in the offspring. Further, no one probably will object to the statement that it implies a dual or duplex condition of the zygote as regards determiners and a simple or simplex condition of the gamete. Thirdly, the fact will be admitted by all that most mendelizing characters are wholly independent of each other in heredity, for which reason we are forced to suppose that their determiners are distinct within the germ-cell. ”

“ Since the female is always heterozygous for F, her gametes must be of two kinds, viz. Fg and fg, while those of the pure grossulariata male must be all fG. When an ovum Fg is fertilised by a spermatozoon fG, the resulting zygote, FfGg, is heterozygous for both F and G, and in appearance is a female grossulariata. The zygote resulting from the fertilisation of an ovum fg by a spermatozoon fG is heterozygous for G, but does not contain F, and therefore is a male grossulariata. Such a male being in constitution {103}ffGg must produce gametes of two kinds, fG and fg, in equal numbers. ”

“ If segregation takes place at the reduction divisions we might suppose that half the gametes formed are sperms and half are ova, and that in the male the latter do not survive but perish and disappear. But in this case it would be the whole of the chromosomes coming from the original female gamete which would disappear, and the spermatozoon would be incapable of transmitting characters derived from the female parent of the individual in which the spermatozoa were formed. An individual could never inherit character from its paternal grandmother. ”

“ An individual is said to be homozygous for a given character when it has been formed by two gametes each bearing the character, and all the gametes of a homozygote bear the character in respect of which it is homozygous. When, however, the zygote is formed by two gametes of which one bears the given character while the other does not, it is said to be heterozygous for the character in question, and only half the gametes produced by such a heterozygote bear the character. An individual may be homozygous for one or more characters, and at the same time may be heterozygous for others. ”

“ It is obvious that after the reduction divisions (second row) the [Pg 63] mature sex-cells of the female will each contain a single normal X, the corresponding sex cells of the male will contain either no X or a defective X. Since if any member of the class of spermatozoa containing no X, fertilizes an egg the resulting zygote (row three) will have but one X and that a normal one, the individual which develops from the zygote will be normal as regards color vision and moreover will be male because the condition one X always means maleness. ”

“ It must be explained that according to this theory the normal male is always heterozygous, because the Y chromosome never carries any other factor except that for sex; it is thus of no more importance than the absence of an X chromosome which occurs in those cases where the male has one sex-chromosome and the female two. ”

“ Hence, if we sow all the seed of each generation, it is seen that each of the homozygote types approaches 25 per cent, of the whole, while all the heterozygote types approach zero, and the larger the number of latent characters in a type, the more rapidly it decreases in proportion. In trihybrids, we should have eight homozygote types, each increasing toward 121⁄2 per cent. of the whole. Hence the generalization, a hybrid of the nth order tends to split up into 2n fixed types, all types not fixed tending to disappear. ”

“ 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 (male) of an entire X chromosome with its contained factors. ”

“ Such a result is produced by random assortment of the chromosomes in gamete and zygote formation, and occurs when the genes for two or more pairs of contrasted characters are located in different chromosome pairs. The phenomenon is formulated in Mendel’s Second Law, the law of independent assortment. The novelty, however, of the true-breeding forms thus produced is not absolute, but relative. There is no origination of new hereditary factors. It is simply a recombination of the old genes of different stocks, the genes themselves undergoing no intrinsic alteration. ”

“ Thus black guinea-pigs of formula BB are duplex with regard to the determiner for black color, individuals of formula Bb are simplex with reference to this determiner, and those of formula bb are nulliplex.
A heterozygote in which dominance prevails can be identified with certainty by breeding to a known recessive and noting the kind of offspring produced. If the individual was really a heterozygote, approximately fifty per cent. of the offspring should be of the recessive type. ”

“ Since there are equal numbers of the spermatozoa with the X-element and without it, and inasmuch as presumably under ordinary conditions one kind is as likely to fertilize the egg as the other, then there are equal chances at fertilization of producing a zygote with two X-elements or with but one.
We have already seen that the former is always female, the latter male. It thus becomes possible to distinguish the sex of an embryo by counting the chromosomes of its cells. ”

“ In the next generation m in the male would be affected, and the male for the sake of simplicity might be supposed to become MMXX. When the female gametes segregated, some would always be mY, and some zygotes therefore MXmY. Others might be MMXY. On this theory, therefore, there would always be some females heterozygous for the male character. ”

“ In the case of balanced lethals (i.e. factors causing death in the pure or homozygous state) , the hybrid phenotype may be maintained even by sexual reproduction, inasmuch as all the pure (homozygous) offspring are non-viable. Two lethals are said to be balanced, when they occur, the first in one and the second in the other homologous chromosome of the same synaptic pair. “Such a factorial situation would maintain a state of constant heterozygosis, the fixed hybridism of an impure species ... ”

“ It is evident from these data that there must be present in the sex-chromosome a gen that causes the death of every male that receives this chromosome, and that this lethal factor lies very close to the factor for white eyes. ”

“ If a heterozygous bird be mated to a recessive the variability of the offspring is much increased, owing to the occurrence in the progeny of both DR and RR individuals (table 40) . The offspring do not, to be sure, fall into two distinct and well-defined types, as in typical Mendelian cases; but one part of the range of variation agrees fairly with that of pure RR's, i. e., Brahmas, and the remainder with that of heterozygotes. ”

“ And since each sex would be equally likely to have these eight types of gametes and any one of the eight in one individual might meet any one of the eight of the other, the possible number of combinations in the production of a new individual from such germ-cells would be 8x8, or 64. With the larger numbers of chromosomes which exist in most animals it is readily seen that the number of possible combinations becomes very great. ”

“ The approach to continuity in variation exhibited by the F2 generation depends upon the fact that these two factors interact upon one another, and to different degrees according as the zygote is for one {129}or other or both of them in a homozygous or a heterozygous state. Moreover, certain of these intermediates will breed true to an intermediate condition of the pigmentation. A male of the constitution ffPPII when bred with females of the constitution FfPPIi will produce only males like itself and females like the maternal parent. ”

“ According to our theory, the ids do not collectively exert a controlling influence on the cells, not even on the germ-cells, whose histological differentiation into spermatic or egg-cells can only depend on control through specific sex-cell determinants. It is the different determinants of the ids that control; transformations of the species will, it is true, depend on transformations of the ids, but this need not necessarily consist in a variation of all the determinants of the id. ”

“ Since the male gamete is very small and seems to contribute to the zygote almost nothing except the chromosomes, which carry with them all the characters of the male parent, it seems a necessary conclusion that the chromosomes alone determine the character of the adult. ”

“ Whatever the nature of the lethals' action, it can be shown that from among the offspring obtained from certain stocks expected classes are missing, and the absence of these classes can be accounted for on the assumption that there are present mutant factors that follow the Mendelian rule of segregation and which show normal linkage to other factors, but whose only recognizable difference from the normal is the death of those individuals which receive them. ”