While fission and fusion can change chromosome number,
these events are quite rare. A more common event that occurs affecting
chromosome number involves a type of meiotic error called non-disjunction.
Non-disjunction describes that situation when chromatids are not equally
distributed among daughter cells during meiosis. Resulting gametes will
have too many or too few chromosomes. If these gametes become part of a
zygote, the resultant individual is said to be aneuploid. Sometimes such
individuals are viable, but often there are developmental problems that
result leading to individuals that are different. Many cases, however,
result in zygotes that do not complete development or do not live long.
If a gamete with an extra chromosome combines with a normal chromosome
to produce a zygote, that zygote is said to be trisomic: such zygotes have
three of one chromosome rather than the usual complement of two. Trisomy-21,
for example, is a fairly common situation in humans, resulting in what
is termed Down's Syndrome. Conversely, monosomy refers to a zygote with
a missing chromosome: it has one of a chromosome rater than the normal
complement of two. Most cases of monosomy result in zygotes that do not
fully develop. Look over the beginning of Ch. 9 to see some other examples
of these phenomena.
Until now, we have concerned ourselves only with
genes that largely conform to the basic Mendelian Model (diploidy, normal
segregation). This holds for genes and chromosomes comprising most of the
genomes of organisms. These chromosomes are termed autosomes. The other
type of chromosomes are called sex chromsomes: not surprisingly, this is
becauase have something to do with the sex of individuals... We will continue
our genetical study by first examining a few sex determination systems,
then look are traits that are associated with or affected by genes on sex
chromosomes: sex-influenced traits, sex-limited traits, and sex-linked
traits. Along the way, we will take a brief look at dosage compensation.
The first suggestion that chromsome types may be
associated with sex determination came from cytological studies of in some
insects. In the late 1800s and early 1900s, work by Henking and by E. B
Wilson on a species where males had an odd number of chromosomes (13) while
females had an even number (14) resulted in an understanding of the details
of this system. It was found by careful microscopic observation that all
female gametes had 7 chromsomes, whereas males produced equal numbers of
gametes with 6 and 7 chromsomes. Further experimental work allowed construction
of the details of what is now known as the XO sex determination system,
found in many species of insects. Females have 6 pairs of autosomes and
1 pair of sex chromsomes. All female gametes have 6 autosomes and 1 sex
chromsome. Males, on the other hand, have 6 pairs of autosomes and a single
sex chromosome. This sex chromsome has no other chromsome to pair with
during meiosis, so half of gametes produced receive a sex chromsomes and
half do not. Therefore males produce two distinct types of gametes, and
are referred to as the heterogametic sex in this system. (Females are referred
to as the homogametic sex.) It is therefore the male gamete that determines
the sex of the zygote: if the sperm has a sex chromsome, the individual
is a female, and vice versa. Henking first referred to the sex chromsomes
as "X-bodies": this resulted in the sex chromsomes in this system being
called X-chromsomes.
Although this was the first sex determination system
discovered, it is not very common. A more common system is called the XY
sex determination system. The cytogenetic characteristics are similar,
except that there is a distinct chromosome type (called the Y-chromsome)
that pairs with the X-chromosome during meiosis. Again, males are heterogametic
and females are homogametic. However, is this system all male gametes have
the same number of chromosomes, but they differ in whether they contain
an X-chromosome or a Y-chromosome. For example, a species with a diploid
number of 20 would have 9 pairs of autosomes and 1 pair of sex chromosomes.
Females would have 18 autosomes and 2 X-chromosomes, whereas males would
have 18 autosomes, 1 X-chromsome, and 1 Y-chromosome.
A third type of chromosomal sex determination, found
in birds, moths, and some fish, is similar except that the famales are
heterogametic and males are homogametic. This is called the ZW system:
males are ZZ and females are ZW.
Although the chromosomal characteristics of species
with XY sex determination are similar, there are substantial differences
in the mechanisms that actually determine sex. We will briefly examine
two of the more well-studies cases: 1) The Genetic Balance System studied
extensively in Drosophila, and 2) the mammalian XY system.
In Drosophila, XY individuals are male and
XX individuals are female. (All individuals have 3 pairs of autosomes.)
However, the presence/absence of the Y-chromsome has no effect on sex:
it is the number of X-chromsomes relative to the number of sets of autosomes
that determines the sex of individuals. This system became understood after
extensive work by C. B. Bridges involving careful examination of chromosomal
complement of individuals that were the result of non-disjunct gametes.
In the following discourse, we will use "A" to refer to the set of autosomes
(3 pairs). Normal males are AAXY and normal females are AAXX. Male gametes
are normally either AX or AY. However, when non-disjunction occurs, there
are many possibilites: A, AX, AY, AXX, AXY, AAX, AAXX, etc. The gamete
will have various combinations of sex chromsomes and autosomes depending
on the exact nature of the non-disjunction. Similarly, females gametes
are normally AX, but with non-disjunction may be A, AXX, AA, AAXX. When
abnormal gametes combine, individuals with abnormal combinations of autosomes
and sex chromsomes will result. Detailed work led to the following obervations
(among many):
Genotype Result
AAXX
normal female
AAXY
normal male
AAAX
male (infertile)
AAAAXX male (polyploid)
AAXXX female (infertile)
AAAAXXX intersex
Bridges and co-workers evaluated these and other data and determined that it was the ratio of autosomal sets to X-chromsomes that determined the sex. This is summarized below:
Ratio
Sex
X/A <= 0.5
male
X/A >= 1.0
female
0.5 < X/A < 1.0 intersex
Because it is a balance of autosomes and sex chromosomes that determines sex, this became known as the Genetic Balance System.
Mammals have XY sex determination, but have a very different underlying mechanism. Again, this system was elucidated by examination of individuals with unusually complements of chromsomes because they came from non-disjunct gametes. The following are some examples (here, we ignore autosomal sets):
Genotype
Sex
XX
male
XY
female
XXX
female
XXY
male
XYY
male
These and and other data indicated that it is the presence of the Y-chromosome
that determines sex. The hypothesis is that a gene on the Y-chromosome
causes embryonic gonadal tissue to develop into testes: in the absence
of this gene, the tissue develops into ovaries. This gene produces what
is called testis determining factor (TDF). Recent work has provided substantial
evidence for this hypothesis:
1) Some individuals that are XX are male and some
that are XY are female. Careful karyological examination indictes that
in these individuals there has been a change in the sex chromosome. In
the first case, a small part of the Y-chromosome has been deleted. In the
latter, there has been a translocation of the same portion of the Y-chromosome
onto one of the X-chromosomes.
2) Work on transgenic mice indicates that the injection
of a specific gene region from that same small part of the Y-chromosome
into a normal XX zygote at an early stage of development results in a normal
male. This region (in mice) has been termed the SRY (sex-determining region).
You may have noticed that in species with XY sex
determination, males have 1 X-chromsome and females have 2 X-chromosomes.
Does this mean that females get a double dose of genes on the X-chromosome?
The answer is no: there is a phenomenon called dosage compensation whereby
one of the X-chromsomes is inactivated in all cells in females. This inactivation
is random, and it is not the same in all cells in the body. Females are
therefore mosaics with respect to genes on the X-chromosome: some tissues
have the paternal X-chrosomes inactivated and others have the maternal
X-chromosome inactivated. How do we know this? This idea is enbodied in
the Lyon Hypothesis, originally formulated by Dr. Mary Lyon. It has been
substantiated in several ways. One way involves the interpretation of banding
patterns that are visible as a result of protein electrophoresis. The enzyme
G-6-PDH occurs on the X-chromosome. It is a dimeric enzyme, meaning that
the functioning enzyme is comprised of two identical subunits, each the
result of translation of the gene. These subunits randomly combine in the
cytoplasm to form functioning enzyme molecules. Females that are heterozygous
can produce two different type of subunits, that can combine in 3 different
ways. If we call these subunits A and B, then it is possible for the functioning
enzyme to be AA (2 A subunits), AB, or BB. Electrophoretically, these are
distinguishable. If an individual has only one active gene in each cell,
then only one type of subunit is present. Therefore, they could only exhibit
AA and BB enymes. If, on the other hand, the same X-chromosome was inactivated
in all cells, then only AA or BB could be produced. If there was no inactivation,
then all 3 types could be found. Electrophoretic results indicate support
for the Lyon Hypothesis: in tissue preparations from some females, both
AA and BB were found, but no AB types were found.
At this point it is useful to interject a bit more
about sex determination. Although we have seen 3 different types of chromosomal
sex determination systems, there are many organisms where the environmental
conditions determine sex. Many reptiles and fish have there sex determined
by the temperature experienced during a specific critical period of development.
Other species, such as.....(drum roll...) Daphnia have
another type of environmental sex determination. In this system, it is
the general environmental condition that determines sex: if food is abundant
and the population is not crowded, only females are produced. If the population
is becoming crowded and food is scarce, males are produced.
However, even though these two systems are not chromsomal,
and are termed ESD (environmental sex determination) it is important to
not that there are genes that affect sex. Genotypes differ in there response
to environmental stimuli in terms of the sex ratio on their offspring.
Therefore, rather that dichotomizing sex determination into Genetic vs.
Environmental, it is probably better to dichotomize between Chromosomal
and Non-chromosomal, and recognize that the latter case consists of a wide
variey of mechanisms with differing degrees of genetic contribution.
The next category of traits are those for which the expression is limited to one or the other sex. An example of this (discussed in class) is a class of lineages of Daphnia pulex, which all contain a mutation which is a sex-limited meiosis suppressor. There is a dominant allele at a locus that, if present, suppresses meiosis in females: it has no effect on males. Therefore, the trait ("meiosis suppression" in this case) is limited to one sex.