THE FACTORIAL THEORY OF HEREDITY AND THE COMPOSITION OF THE GERM PLASM
The discovery that Mendel made with edible peas concerning heredity has
been found to apply everywhere throughout the plant and animal kingdoms--to
flowering plants, to insects, snails, crustacea, fishes, amphibians, birds,
and mammals (including man).
There must be something that these widely separated groups of plants and
animals have in common--some simple mechanism perhaps--to give such
definite and orderly series of results. There is, in fact, a mechanism,
possessed alike by animals and plants, that fulfills every requirement of
Mendel's principles.
THE CELLULAR BASIS OF ORGANIC EVOLUTION AND HEREDITY
In order to appreciate the full force of the evidence, let me first pass
rapidly in review a few familiar, historical facts, that preceded the
discovery of the mechanism in question.
[Illustration: FIG. 45. Typical cell showing the cell wall, the protoplasm
(with its contained materials); the nucleus with its contained chromatin
and nuclear sap. (After Dahlgren.)]
Throughout the greater part of the last century, while students of
evolution and of heredity were engaged in what I may call the more general,
or, shall I say, the _grosser_ aspects of the subject, there existed
another group of students who were engaged in working out the minute
structure of the material basis of the living organism. They found that
organs such as the brain, the heart, the liver, the lungs, the kidneys,
etc., are not themselves the units of structure, but that all these organs
can be reduced to a simpler unit that repeats itself a thousand-fold in
every organ. We call this unit a cell (fig. 45).
The egg is a cell, and the spermatozoon is a cell. The act of fertilization
is the union of two cells (fig. 47, upper figure). Simple as the process of
fertilization appears to us today, its discovery swept aside a vast amount
of mystical speculation concerning the role of the male and of the female
in the act of procreation.
Within the cell a new microcosm was revealed. Every cell was found to
contain a spherical body called the nucleus (fig. 46a). Within the nucleus
is a network of fibres, a sap fills the interstices of the network. The
network resolves itself into a definite number of threads at each division
of the cell (fig. 46 b-e). These threads we call chromosomes. Each species
of animals and plants possesses a characteristic number of these threads
which have a definite size and sometimes a specific shape and even
characteristic granules at different levels. Beyond this point our
strongest microscopes fail to penetrate. Observation has reached, for the
time being, its limit.
[Illustration: FIG. 46. A series of cells in process of cell division. The
chromosomes are the black threads and rods. (After Dahlgren.)]
The story is taken up at this point by a new set of students who have
worked in an entirely different field. Certain observations and experiments
that we have not time to consider now, led a number of biologists to
conclude that the chromosomes are the bearers of the hereditary units. If
so, there should be many such units carried by _each_ chromosome, for the
number of chromosomes is limited while the number of independently
inherited characters is large. In Drosophila it has been demonstrated not
only that there are exactly as many groups of characters that are inherited
together as there are pairs of chromosomes, but even that it is possible to
locate one of these groups in a particular chromosome and to state the
_relative position_ there of the factors for the characters. If the
validity of this evidence is accepted, the study of the cell leads us
finally in a mechanical, but not in a chemical sense, to the ultimate units
about which the whole process of the transmission of the hereditary factors
centers.
But before plunging into this somewhat technical matter (that is difficult
only because it is unfamiliar), certain facts which are familiar for the
most part should be recalled, because on these turns the whole of the
subsequent story.
[Illustration: FIG. 47. An egg, and the division of the egg--the so-called
process of cleavage. (After Selenka.)]
The thousands of cells that make up the cell-state that we call an animal
or plant come from the fertilized egg. An hour or two after fertilization
the egg divides into two cells (fig. 47). Then each half divides again.
Each quarter next divides. The process continues until a large number of
cells is formed and out of these organs mould themselves.
[Illustration: FIG. 48. Section of the egg of the beetle, Calligrapha,
showing the pigment at one end where the germ cells will later develop as
shown in the other two figures. (After Hegner.)]
At every division of the cell the chromosomes also divide. Half of these
have come from the mother, half from the father. Every cell contains,
therefore, the sum total of all the chromosomes, and if these are the
bearers of the hereditary qualities, every cell in the body, whatever its
function, has a common inheritance.
At an early stage in the development of the animal certain cells are set
apart to form the organs of reproduction. In some animals these cells can
be identified early in the cleavage (fig. 48).
The reproductive cells are at first like all the other cells in the body in
that they contain a full complement of chromosomes, half paternal and half
maternal in origin (fig. 49). They divide as do the other cells of the body
for a long time (fig. 49, upper row). At each division each chromosome
splits lengthwise and its halves migrate to opposite poles of the spindle
(fig. 49 c).
But there comes a time when a new process appears in the germ cells (fig 49
e-h). It is essentially the same in the egg and in the sperm cells. The
discovery of this process we owe to the laborious researches of many
workers in many countries. The list of their names is long, and I shall not
even attempt to repeat it. The chromosomes come together in pairs (fig. 49
a). Each maternal chromosome mates with a paternal chromosome of the same
kind.
[Illustration: FIG. 49. In the upper row of the diagram a typical process
of nuclear division, such as takes place in the early germ cells or in the
body cells. In the lower row the separation of the chromosomes that have
paired. This sort of separation takes place at one of the two reduction
divisions.]
Then follow two rapid divisions (fig. 49 f, g and 50 and 51). At one of the
divisions the double chromosomes separate so that each resulting cell comes
to contain some maternal and some paternal chromosomes, i.e. one or the
other member of each pair. At the other division each chromosome simply
splits as in ordinary cell division.
[Illustration: FIG. 50. The two maturation divisions of the sperm cell.
Four sperms result, each with half (haploid) the full number (diploid) of
chromosomes.]
The upshot of the process is that the ripe eggs (fig. 51) and the ripe
spermatozoa (fig. 50) come to contain only half the total number of
chromosomes.
[Illustration: FIG. 51. The two maturation divisions of the egg. The
divisions are unequal, so that two small polar bodies are formed one of
these subsequently divides. The three polar bodies and the egg are
comparable to the four sperms.]
When the eggs are fertilized the whole number of chromosomes is restored
again.
THE MECHANISM OF MENDELIAN HEREDITY DISCOVERED IN THE BEHAVIOR OF THE
CHROMOSOMES
If the factors in heredity are carried in the chromosomes and if the
chromosomes are definite structures, we should anticipate that there should
be as many _groups_ of characters as there are kinds of chromosomes. In
only one case has a sufficient number of characters been studied to show
whether there is any correspondence between the number of hereditary groups
of characters and the number of chromosomes. In the fruit fly, Drosophila
ampelophila, we have found about 125 characters that are inherited in a
perfectly definite way. On the opposite page is a list of some of them.
It will be observed in this list that the characters are arranged in four
groups, Groups I, II, III and IV. Three of these groups are equally large
or nearly so; Group IV contains only two characters. The characters are put
into these groups because in heredity the members of each group tend to be
inherited together, i.e., if two or more enter the cross together they tend
to remain together through subsequent generations. On the other hand, any
member of one group is inherited entirely independently of any member of
the other groups; in the same way as Mendel's yellow-green pair of
characters is inherited independently of the round-wrinkled pair.
_Group I_ _Group II_ _Group III_ _Group IV_
Abnormal Antlered Band Bent
Bar Apterous Beaded Eyeless
Bifid Arc Cream III
Bow Balloon Deformed
Cherry Black Dwarf
Chrome Blistered Ebony
Cleft Comma Giant
Club Confluent Kidney
Depressed Cream II Low crossing over
Dot Curved Maroon
Eosin Dachs Peach
Facet Extra vein Pink
Forked Fringed Rough
Furrowed Jaunty Safranin
Fused Limited Sepia
Green Little crossover Sooty
Jaunty Morula Spineless
Lemon Olive Spread
Lethals, 13 Plexus Trident
Miniature Purple Truncate intensifier
Notch Speck Whitehead
Reduplicated Strap White ocelli
Ruby Streak
Rudimentary Trefoil
Sable Truncate
Shifted Vestigial
Short
Skee
Spoon
Spot
Tan
Truncate intensifier
Vermilion
White
Yellow
If the factors for these characters are carried by the chromosomes, then we
should expect that those factors that are carried by the same chromosome
would be inherited together, provided the chromosomes are definite
structures in the cell.
[Illustration: FIG. 52. Chromosomes (diploid) of D. ampelophila. The sex
chromosomes are XX in the female and XY in the male. There are three other
pairs of chromosomes.]
In the chromosome group of Drosophila, (fig. 52) there are _four_ pairs of
chromosomes, three of nearly the same size and one much smaller. Not only
is there agreement between the number of hereditary groups and the number
of the chromosomes, but even the size relations are the same, for there are
three great groups of characters and three pairs of large chromosomes, and
one small group of characters and one pair of small chromosomes.
THE FOUR GREAT LINKAGE GROUPS OF DROSOPHILA AMPELOPHILA
The following description of the characters of the wild fly may be useful
in connection with the account of the modifications of these characters
that appear in the mutants.
The head and thorax of the wild fly are grayish-yellow, the abdomen is
banded with alternate stripes of yellow and black. In the male, (fig. 4 to
right), there are three narrow bands and a black tip. In the female there
are five black bands (fig. 4 to left). The wings are gray with a surface
texture of such a kind that at certain angles they are iridescent. The eyes
are a deep, solid, brick-red. The minute hairs that cover the body have a
very definite arrangement that is most obvious on the head and thorax.
There is a definite number of larger hairs called bristles or chaetae which
have a characteristic position and are used for diagnostic purposes in
classifying the species. On the foreleg of the male there is a comb-like
organ formed by a row of bristles; it is absent in the female. The comb is
a secondary sexual character, and it is, so far as known, functionless.
Some of the characters of the mutant types are shown in figures 53, 54, 55,
56. The drawing of a single fly is often used here to illustrate more than
one character. This is done to economize space, but of course there would
be no difficulty in actually bringing together in the same individual any
two or more characters belonging to the same group (or to different
groups). Without colored figures it is not possible to show many of the
most striking differences of these mutant races; at most dark and light
coloring can be indicated by the shading of the body, wings, or eyes.
_Group I_
In the six flies drawn in figure 53 there are shown five different wing
characters. The first of these types (a) is called cut, because the ends of
the wings look as though they had been cut to a point. The antennae are
displaced downward and appressed and their bristle-like aristae are
crumpled.
[Illustration: FIG. 53. Group I. (See text)]
The second figure (b) represents a fly with a notch in the ends of the
wings. This character is dominant, but the same factor that produces the
notch in the wings is also a recessive lethal factor; because of this
latter effect of the character no males of this race exist, and the females
of the race are never pure but hybrid. Every female with notch wings bred
to a wild male, will produce in equal numbers notch winged daughters and
daughters with normal wings. There will be half as many sons as daughters.
The explanation of this peculiar result is quite simple. Every notch winged
female has one X chromosome that carries the factor for notch and one X
chromosome that is "normal". Daughters receiving the former chromosomes are
notched because the factor for notch is dominant, but they are not killed
since the lethal effect of the notch factor is recessive to the normal
allelomorph carried by the other chromosome that the daughters get from
their father. This normal factor is recessive for notch but dominant for
life. This same figure (b) is used here to show three other sex linked
characters. The spines on the thorax are twisted or kinky, which is due to
a factor called "forked". The effect is best seen on the thorax, but all
spines on the body are similarly modified; even the minute hairs are also
affected. Ruby eye color might be here represented--if the eyes in the
figure were colored. The lighter color of the body and antennae is intended
to indicate that the character tan is also present. The light color of the
antennae is the most certain way of identifying tan. The tan flies are
interesting because they have lost the positive heliotropism that is so
marked a feature in the behavior of D. ampelophila. As this peculiarity of
the tan flies is inherited like all the other sex linked characters, it
follows that when a tan female is bred to a wild male all the sons inherit
the recessive tan color and indifference to light, while the daughters show
the dominant sex linked character of their father, i.e., they are "gray",
and go to the light. Hence when such a brood is disturbed the females fly
to the light, but the males remain behind.
One of the first mutants that appeared in D. ampelophila was called
rudimentary on account of the condition of the wings (c). The same mutation
has appeared independently several times. In the drawing (c) the dark body
color is intended to indicate "sable" and the lighter color of the eyes is
intended to indicate eosin. This eye color, which is an allelomorph of
white, is also interesting because in the female the color is deeper than
in the male. In other cases of sex linked factors the character is the same
in the two sexes.
In the fourth figure (d) the third and fourth longitudinal veins of the
wing are _fused_ into one vein from the base of the wing to the level of
the first cross-vein and in addition converge and meet near their outer
ends. The shape of the eye is represented in the figure as different from
the normal, due to another factor called "bar". This is a dominant
character, the hybrid condition being also narrow, but not so narrow as the
pure type. Vermilion eye color might also be here represented--due to a
factor that has appeared independently on several occasions.
In the fifth figure (e) the wings are shorter and more pointed than in the
wild fly. This character is called miniature. The light color of the
drawing may be taken to represent yellow body color, and the light color of
the eye white eye color.
In the last figure (f) the wings are represented as pads, essentially in
the same condition that they are in when the fly emerges from the pupa
case. Not all the flies of this stock have the wings in this condition;
some have fully expanded wings that appear normal in all respects.
Nevertheless, about the same percentage of offspring show the pads
irrespective of whether the parents had pads or expanded wings.
The flies of this stock show, however, another character, which is a
product of the same factor, and which is constant, i.e., repeated in all
individuals. The two bristles on the sides of the thorax are constantly
absent in this race. The lighter color of the eye in the figure may be
taken to indicate buff--a faint yellowish color. The factor for this eye
color is another allelomorph of white.
There are many other interesting characters that belong to the first group,
such as abnormal abdomen, short legs, duplication of the legs, etc. In
fact, any part of the body may be affected by a sex-linked factor.
_Group II_
In the first figure (a) of figure 54 that contains members of Group II the
wings are almost entirely absent or "vestigial". This condition arose at a
single step and breeds true, although it appears to be influenced to some
extent by temperature, also by modifiers that sometimes appear in the
stock. Purple eye color belongs in Group II; it resembles the color of the
eye of the wild fly but is darker and more translucent.
[Illustration: FIG. 54. Group II. (See text.)]
In the second figure (b) the wing is again long and narrow and sometimes
bent back on itself, as shown here. In several respects the wing resembles
strap (d) but seems to be due to another factor, called antler,
insufficiently studied as yet.
In the third figure (c) the wings turn up at the end. This is brought about
by the presence of the factor called jaunty.
In the fourth figure the wings are long and narrow and several of the veins
are unrepresented. This character, "strap", is very variable and has not
yet been thoroughly studied. On the thorax there is a deep black mark
called trefoil. Even in the wild fly there is a three pronged mark on the
thorax present in many individuals. Trefoil is a further development and
modification of this mark and is due to a special factor.
In the fifth figure (e) the wings are arched. The factor is called arc. The
dark color of the body, and especially of the wings, indicates the factor
for black.
The sixth figure (f) shows the wings "curved" downwards. In addition there
is present a minute black speck at the base of each wing, due to another
factor called speck.
In the seventh figure (g) the wing is truncate. Its end is obliquely
squared instead of rounded; it may be longer than the body, or shorter when
other modifying factors are present. The mutation that produces this type
of wing is of not infrequent occurrence. It has been shown by Muller and
Altenburg that there are at least two factors that modify this
character--the chief factor is present in the second chromosome; alone it
produces the truncate wing in only a certain percentage of cases, but when
the modifiers are also present about ninety percent of the individuals may
show the truncate condition of the wing. But the presence of these factors
makes the stock very infertile, so that it is difficult to maintain.
In the eighth figure (h) the legs are shortened owing to the absence of a
segment of the tarsus. The stock is called dachs--a nickname given to it
because the short legs suggested the dachshund.
_Group III_
In figure 55, (a), a mutant type called bithorax is shown. The old
metathorax is replaced by another mesothorax thrust in between the normal
mesothorax and the abdomen. It carries a pair of wings that do not
completely unfold. On this new mesothorax the characteristic arrangement of
the bristles is shown. Thus at a single step a typical region of the body
has doubled. The character is recessive.
[Illustration: FIG. 55. Group III. (See text.)]
The size of the adult fly of D. ampelophila varies greatly according to the
amount of nourishment obtained by the larva. After the fly emerges its size
remains nearly constant, as in many insects. Two races have, however, been
separated by Bridges that are different in size as a result of a genetic
factor. The first of these, called dwarf, is represented by figure 55, (b).
The race is minute, although of course its size is variable, depending on
food and other conditions. The same figure shows the presence of another
factor, "sooty", that makes the fly very dark. Maroon eye color might be
here represented, due to still another factor.
In the third figure (c) the other mutation in size is shown. It is called
"giant". The flies are twice the size of wild flies. An eye color, called
peach, might here be represented. It is an allelomorph of pink.
In the fourth figure (d) the mutant called dichaete is shown. It is
characterized by the absence of two of the bristles on the thorax. Other
bristles may also be absent, but not so constantly as the two just
mentioned. Another effect of the same factor is the spread-out condition of
the wings. The very dark eye color in this figure may be taken to indicate
the presence of another factor, "sepia", which causes the eyes to assume a
brown color that becomes black with age. Most of the other mutations in eye
color that have occurred tend to give a lighter color: this one, which is
also recessive, makes the eye darker.
In the fifth figure (e) the color of the darkest fly is due to a factor
called ebony, which is an allelomorph of sooty.
In the sixth figure (f) the wings are beaded, i.e., the margin is defective
at intervals, giving a beaded-like outline to the wings. This condition is
very variable and much affected by other factors that influence the shape
of the wings. The lighter eye color of the drawing may be taken to
represent pink.
In the seventh figure (g) the wings are curled up over the back. This is a
recessive character.
_Group IV_
Only two mutants have been obtained that do not belong to any of the
preceding groups; these are put together in Group IV. It has been shown
that they are linked to each other and the linkage is so close that it has
thus far been impossible to obtain the dominant recessive. One of these
mutants, called "eyeless" (fig. 56, a, a^1), is variable--the eyes are
often entirely absent or represented by one or more groups of ommatidia.
The outline of the original eye, so to speak, is strongly marked out and
its area might be called a rudimentary organ, if such a statement has any
meaning here.
[Illustration: FIG. 56. Group IV. (See text.)]
The other figure (b) represents "bent", so called from the shape of the
wings. This mutant is likewise very variable, often indistinguishable from
the wild type, yet when well developed strikingly different from any other
mutant.
This brief account of a few of the mutant races that can be most easily
represented by uncolored figures will serve to show how all parts of the
body may change, some of the changes being so slight that they would be
overlooked except by an expert, others so great that in the character
affected the flies depart far from the original species.
_It is important to note that mutations in the first chromosome are not
limited to any part of the body nor do they affect more frequently a
particular part. The same statement holds equally for all of the other
chromosomes. In fact, since each factor may affect visibly several parts of
the body at the same time there are no grounds for expecting any special
relation between a given chromosome and special regions of the body. It can
not too insistently be urged that when we say a character is the product of
a particular factor we mean no more than that it is the most conspicuous
effect of the factor._
If, then, as these and other results to be described point to the
chromosomes as the bearers of the Mendelian factors, and if, as will be
shown presently, these factors have a definite location in the chromosomes
it is clear that the location of the factors in the chromosomes bears no
spatial relation to the location of the parts of the body to each other.
LOCALIZATION OF FACTORS IN THE CHROMOSOMES
_The Evidence from Sex Linked Inheritance_
When we follow the history of pairs of chromosomes we find that their
distribution in successive generations is paralleled by the inheritance of
Mendelian characters. This is best shown in the sex chromosomes (fig. 57).
In the female there are two of these chromosomes that we call the X
chromosomes; in the male there are also two but one differs from those of
the female in its shape, and in the fact that it carries none of the normal
allelomorphs of the mutant factors. It is called the Y chromosome.
The course followed by the sex chromosomes and that by the characters in
the case of sex linked inheritance are shown in the next diagram of
Drosophila illustrating a cross between a white eyed male and a red eyed
female.
[Illustration: FIG. 57. Scheme of sex determination in Drosophila type.
Each _mature_ egg contains one X, each mature sperm contains one X, or a Y
chromosome. Chance union of any egg with any sperm will give either XX
(female) or XY (male).]
[Illustration: FIG. 58. Cross between white eyed male of D. ampelophila and
red eyed female. The sex chromosomes are indicated by the rods. A black rod
indicates that the chromosome carries the factor for red; the open
chromosome the factor for white eye color.]
The first of these represents a cross between a white eyed male and a red
eyed female (fig. 58, top row). The X chromosome in the male is represented
by an open bar, the Y chromosome is bent. In the female the two X
chromosomes are black. Each egg of such a female will contain one "black" X
after the polar bodies have been thrown off. In the male there will be two
classes of sperm--the female-producing, carrying the (open) X, and the
male-producing, carrying the Y chromosome. Any egg fertilized by an X
bearing sperm will produce a female that will have red eyes because the X
(black) chromosome it gets from the mother carries the dominant factor for
red. Any egg fertilized by a Y-bearing sperm will produce a male that will
also have red eyes because he gets his (black) X chromosome from his
mother.
When, then, these two F_1 flies (second row) are inbred the following
combinations are expected. Each egg will contain a black X (red eye
producing) or a white X (white eye producing) after the polar bodies have
been extruded. The male will produce two kinds of sperms, of which the
female producing will contain a black X (red eye producing). Since any egg
may by chance be fertilized by any sperm there will result the four classes
of individuals shown on the bottom row of the diagram. All the females will
have red eyes, because irrespective of the two kinds of eggs involved all
the female-producing sperm carry a black X. Half of the males have red eyes
because half of the eggs have had each a red-producing X chromosome. The
other half of the males have white eyes, because the other half of the eggs
had each a white-producing X chromosome. Other evidence has shown that the
Y chromosome of the male is indifferent, so far as these Mendelian factors
are concerned.
[Illustration: FIG. 59. Cross between red eyed male and white eyed female;
reciprocal cross of Fig. 58.]
The reciprocal experiment is illustrated in figure 59. A white eyed female
is mated to a red eyed male (top row). All the mature eggs of such a female
contain one white-producing X chromosome represented by the open bar in the
diagram. The red eyed male contains female-producing X-bearing sperm that
carry the factor for red eye color, and male-producing Y chromosomes. Any
egg fertilized by an X-bearing sperm will become a red eyed female because
the X chromosome that comes from the father carries the dominant factor for
red eye color. Any egg fertilized by a Y-bearing sperm will become a male
with white eyes because the only X chromosome that the male contains comes
from his mother and is white producing.
When these two F_1 flies are inbred (middle row) the following combinations
are expected. Half the eggs will contain each a white producing X
chromosome and half red producing. The female-producing sperms will each
contain a white X and the male-producing sperms will each contain an
indifferent Y chromosome. Chance meetings of egg and sperm will give the
four F_2 classes (bottom row). These consist of white eyed and red eyed
females and white eyed and red eyed males. The ratio here is 1:1 and not
three to one (3:1) as in other Mendelian cases. But Mendel's law of
segregation is not transgressed, as the preceding analysis has shown; for,
the chromosomes have followed strictly the course laid down on Mendel's
principle for the distribution of factors. The peculiar result in this case
is due to the fact that the F_1 male gets his single factor for eye color
from his mother only and it is linked to or contained in a body (the X
chromosome) that is involved in producing the females, while the mate of
this body--the Y chromosome--is indifferent with regard to these factors,
yet active as a mate to X in synapsis.
[Illustration: FIG. 60. Diagram of sex determination in type with XX female
and XO male (after Wilson).]
In man there are several characters that show exactly this same kind of
inheritance. Color blindness, or at least certain kinds of color blindness,
appear to follow the same scheme. A color blind father transmits through
his daughters his peculiarity to half of his grandsons, but to none of his
grand-daughters (fig. 38A). The result is the same as in the case of the
white eyed male of Drosophila. Color blind women are rather unusual, which
is expected from the method of inheritance of this character, but in the
few known cases where such color blind women have married normal husbands
the sons have inherited the peculiarity from the mother (fig. 38B). Here
again the result is the same as for the similar combination in Drosophila.
[Illustration: FIG. 61. Spermatogenesis in man. There are 47 chromosomes
(diploid) in the male. After reduction half of the sperm carry 24
chromosomes (one of which is X) and half carry 23 chromosomes (no X).]
In man the sex formula appears to be XX for the female and XO for the male
(fig. 60), and since the relation is essentially the same as that in
Drosophila the chromosome explanation is the same. According to von
Winiwarter there are 48 chromosomes in the female and 47 in the male (fig.
61). After the extrusion of the polar bodies there are 24 chromosomes in
the egg. In the male at one of the two maturation divisions the X
chromosome passes to one pole undivided (fig. 61, C). In consequence there
are two classes of sperms in man; female producing containing 24
chromosomes, and male producing containing 23 chromosomes. If the factor
for color blindness is carried by the X chromosome its inheritance in man
works out on the same chromosome scheme and in the same way as does white
eye color (or any other sex linked character) in the fly, for the O sperm
in man is equivalent to the Y sperm in the fly.
In these cases we have been dealing with a single pair of characters. Let
us now take a case where two pairs of sex linked characters enter the cross
at the same time, and preferably a case where the two recessives enter the
cross from the same parent.
If a female with white eyes and yellow wings is crossed to a wild male with
red eyes and gray wings (fig. 62), the sons are yellow and have white eyes
and the daughters are gray and have red eyes. If two F_1 flies are mated
they will produce the following classes.
[Illustration: FIG. 62. Cross between a white eyed, yellow winged female of
D. ampelophila and a red eyed, gray winged male. Two pairs of sex linked
characters, viz., white-red and yellow-gray are involved. (See text.)]
Yellow Gray Yellow Gray
White Red Red White
------------ -------------
| |
99.% 1.%
Not only have the two grandparental combinations reappeared, but in
addition two new combinations, viz., grey white and yellow red. The two
original combinations far exceed in numbers the new or exchange
combinations. If we follow the history of the X chromosomes we discover
that the _larger classes_ of grandchildren appear in accord with the way in
which the X chromosomes are transmitted from one generation to the next.
The _smaller classes_ of grandchildren, the exchange combinations or
cross-overs, as we call them, can be explained by the assumption that at
some stage in their history an interchange of parts has taken place between
the chromosomes. This is indicated in the diagrams.
The most important fact brought out by the experiment is that the factors
that went in together tend to stick together. It makes no difference in
what combination the members of the two pairs of characters enter, they
tend to remain in that combination.
If one admits that the sex chromosomes carry these factors for the
sex-linked characters--and the evidence is certainly very strong in favor
of this view--it follows necessarily from these facts that at some time in
their history there has been an interchange between the two sex chromosomes
in the female.
There are several stages in the conjugation of the chromosomes at which
such an interchange between the members of a pair might occur. There is
further a small amount of direct evidence, unfortunately very meagre at
present, showing that an interchange does actually occur.
At the ripening period of the germ cell the members of each pair of
chromosomes come together (fig. 49, e). In several forms they have been
described as meeting at one end and then progressively coming to lie side
by side as shown in fig. 63, e, f, g, h, i. At the end of the process they
appear to have completely united along their length (fig. 63, j, k, l). It
is always a maternal and a paternal chromosome that meet in this way and
always two of the same kind. It has been observed that as the members of a
pair come together they occasionally twist around each other (fig. 63, g,
l, and 64, and 65). In consequence a part of one chromosome comes to be now
on one side and now on the other side of its mate.
[Illustration: FIG. 63. Conjugation of chromosomes (side to side union) in
the spermatogenesis of Batracoseps. (After Janssens.)]
When the chromosomes separate at the next division of the germ cell the
part on one side passes to one pole, the part on the other to the opposite
pole, (figs. 64 and 65). Whenever the chromosomes do not untwist at this
time there must result an interchange of pieces where they were crossed
over each other.
[Illustration: FIG. 64. Scheme to illustrate a method of crossing over of
the chromosomes.]
Janssens has found at the time of separation evidence in favor of the view
that some such interchange probably takes place.
We find this same process of interchange of characters taking place in each
of the other three groups of Drosophila. An example will show this for the
Group II.
[Illustration: FIG. 65. Scheme to illustrate double crossing over.]
If a black vestigial male is crossed to a gray long-winged female (fig. 66)
the offspring are gray long. If an F_1 female is back-crossed to a black
vestigial male the following kinds of flies are produced:
Black Gray Black Gray
vestigial long long vestigial
----------------- -----------------
| |
83% 17%
The combinations that entered are more common in the F_2 generations than
the cross-over classes, showing that there is linkage of the factors that
entered together.
Another curious fact is brought out if instead of back-crossing the F_1
female we back-cross the F_1 male to a black vestigial female. Their
offspring are now of only two kinds, black vestigial and gray long. This
means that in the male there is no crossing-over or interchange of pieces.
This relation holds not only for the Group II but for all the other groups
as well.
Why interchange takes place in the female of Drosophila and not in the male
we do not know at present. We might surmise that when in the male the
members of a pair come together they do not twist around each other, hence
no crossing-over results.
[Illustration: FIG. 66. Cross between black vestigial and gray long flies.
Two pairs of factors involved in the second group. The F_1 female is back
crossed (to right) to black vestigial male; and the F_1 male is back
crossed to black vestigial female (to left). Crossing over takes place in
the F_1 female but not in the F_1 male.]
Crossing-over took place between white and yellow only once in a hundred
times. Other characters show different values, but the same value under the
same conditions is obtained from the same pair of characters.
[Illustration: FIG. 67. Map of four chromosomes of D. ampelophila locating
those factors in each group that have been most fully studied.]
If we assume that the nearer together the factors lie in the chromosome the
less likely is a twist to occur between them, and conversely the farther
apart they lie the more likely is a twist to occur between them, we can
understand how the linkage is different for different pairs of factors.
On this basis we have made out chromosomal maps for each chromosome (fig.
67). The diagram indicates those loci that have been most accurately
placed.
_The Evidence from Interference_
There is a considerable body of information that we have obtained that
corroborates the location of the factors in the chromosome. This evidence
is too technical to take up in any detail, but there is one result that is
so important that I must attempt to explain it. If, as I assume, crossing
over is brought about by twisting of the chromosomes, and if owing to the
material of the chromosomes there is a most frequent distance of internode,
then, when crossing over between nodes takes place at same level at a-b in
figure 68, the region on each side of that point, a to A and b to B, should
be protected, so to speak, from further crossing over. This in fact we have
found to be the case. No other explanation so far proposed will account for
this extraordinary relation.
[Illustration: FIG. 68. Scheme to indicate that when the members of a pair
of chromosomes cross (at a-b) the region on each side is protected
inversely to the distance from a-b.]
What advantage, may be asked, is there in obtaining numerical data of this
kind? It is this:--whenever a new character appears we need only determine
in which of the four groups it lies and its distance from two members
within that group. With this information we can predict with a high degree
of probability what results it will give with any other member of any
group. Thus we can do on paper what would require many months of labor by
making the actual experiment. In a word we can predict what will happen in
a situation where prediction is impossible without this numerical
information.
_The Evidence from Non-Disjunction_
In the course of the work on Drosophila exceptions appeared in one strain
where certain individuals did not conform to the scheme of sex linked
inheritance. For a moment the hypothesis seemed to fail, but a careful
examination led to the suspicion that in this strain something had happened
to the sex chromosomes. It was seen that if in some way the X chromosomes
failed to disjoin in certain eggs, the exceptions could be explained. The
analysis led to the suggestion that if the Y chromosome had got into the
female line the results would be accounted for, since its presence there
would be expected to cause this peculiar non-disjunction of the X
chromosomes.
That this was the explanation was shown when the material was examined. The
females that gave these results were found by Bridges to have two X's and a
Y chromosome.
The normal chromosome group of the female is shown in figure 52 and the
chromosome group of one of the exceptional females is shown in figure 69.
In a female of this kind there are three sex chromosomes X X Y which are
homologous in the sense that in normal individuals the two present are
mates and separate at the reduction division. If in the X X Y individual X
and X conjugate and separate at reduction and the unmated Y is free to move
to either pole of the spindle, two kinds of mature eggs will result, viz.,
X and XY. If, on the other hand, X and Y conjugate and separate at
reduction and the remaining X is free to go to either pole, four kinds of
eggs will result--XY--X--XX--Y. As a total result four kinds of eggs are
expected: viz. many XY and X eggs and a few XX and Y eggs.
[Illustration: FIG. 69. Figure of the chromosome group of an XXY female,
that gives non-disjunction.]
These four kinds of eggs may be fertilized either by female-producing
sperms or male-producing sperms, as indicated in the diagram (fig. 70).
[Illustration: FIG. 70. Scheme showing the results of fertilizing white
bearing eggs (4 kinds) resulting from non-disjunction. The upper half of
the diagram gives the results when these eggs are fertilized by normal red
bearing, female producing sperm, the lower half by normal, male producing
sperm.]
If such an XXY female carried white bearing Xs (open X in the figures), and
the male carried a red bearing X (black X in the figures) it will be seen
that there should result an exceptional class of sons that are red, and an
exceptional class of daughters that are white. Tests of these exceptions
show that they behave subsequently in heredity as their composition
requires. Other tests may also be made of the other classes of offspring.
Bridges has shown that they fulfill all the requirements predicted. Thus a
result that seemed in contradiction with the chromosome hypothesis has
turned out to give a brilliant confirmation of that theory both genetically
and cytologically.
HOW MANY GENETIC FACTORS ARE THERE IN THE GERM-PLASM OF A SINGLE INDIVIDUAL
In passing I invite your attention to a speculation based on our maps of
the chromosomes--a speculation which I must insist does not pretend to be
more than a guess but has at least the interest of being the first guess
that we have ever been in position to make as to how many factors go
towards the makeup of the germ plasm.
We have found practically no factors less than .04 of a unit apart. If our
map includes the entire length of the chromosomes and if we assume factors
are uniformly distributed along the chromosome at distances equal to the
shortest distance yet observed, viz. .04, then we can calculate roughly how
many hereditary factors there are in Drosophila. The calculation gives
about 7500 factors. The reader should be cautioned against accepting the
above assumptions as strictly true, for crossing-over values are known to
differ according to different environmental conditions (as shown by Bridges
for age), and to differ even in different parts of the chromosome as a
result of the presence of specific genetic factors (as shown by
Sturtevant). Since all the chromosomes except the X chromosomes are double
we must double our estimate to give the _total_ number of factors, but the
half number is the number of the different kinds of factors of Drosophila.
CONCLUSIONS
I have passed in review a long series of researches as to the nature of the
hereditary material. We have in consequence of this work arrived within
sight of a result that seemed a few years ago far beyond our reach. The
mechanism of heredity has, I think, been discovered--discovered not by a
flash of intuition but as the result of patient and careful study of the
evidence itself.
With the discovery of this mechanism I venture the opinion that the problem
of heredity has been solved. We know how the factors carried by the parents
are sorted out to the germ cells. The explanation does not pretend to state
how factors arise or how they influence the development of the embryo. But
these have never been an integral part of the doctrine of heredity. The
problems which they present must be worked out in their own field. So, I
repeat, the mechanism of the chromosomes offers a satisfactory solution of
the traditional problem of heredity.
* * * * *