Chapter 6

Chromosomes and Mendelism

Chromosomes were discovered in the late nineteenth century.
With the aid of a light microscope, chromosomes were observed within the nuclei of cells that have a nucleus.
Each species' chromosomes are distinguishable in number and physical appearance.
At times when cell division is not imminent, chromosomes appear as a diffuse network of fine threads within the nucleus referred to as chromatin.
When cell division nears, chromatin of each chromosome condenses to form the distinguishable structures that can help characterize a species.
- Some regions of the chromatin are dark staining and are more tightly packaged during interphase than other regions. These are called heterochromatin.
- Euchromatin is less densely packaged when compared to heterochromatin.
  - Hetero means different.
  - Eu means true.
Chromosomes, except sex chromosomes, exist in pairs in diploid organisms like humans and garden peas.
Gametes have just half the number and are called haploid.
Many plants and animals tolerate a change in the number of complete sets of chromosomes.
If there are four sets, the organism is called a tetraploid.
If eight sets, the organism is called an octoploid.

Sex chromosomes are an exception to the pair rules for diploids

Females have a pair of sex chromosomes but males have a mismatch set, an X and what is called a y. (In fact the y-chromosome looks like a small X chromosome when viewed with a microscope.) (Figure 5.2)
Males of some species have an O, not a y chromosome. The O actually denotes no chromosome at all. (Figure 5.1 a and b)
In humans, sperm carry either an X or a y, not both .
Therefore, in humans, sex is dictated by the sperm that penetrates the egg.
In birds, it is the reverse. The eggs are heterogametic, each having either a W or a Z chromosome. (Figure 5.17)
Honeybee males are haploid and develop from unfertilized eggs. The females are diploid and develop from fertilized eggs.
In Drosophila, sex is determined by the ratio of X-chromosomes to sets of autosomes (non-sex chromosomes).

Chromosomal Theory of Heredity

Around 1910, biologists began to suspect that genes were associated with chromosomes.
It was suspected that genes were composed of protein. Chromosomes are composed of protein as well as DNA.
It was observed that during meiosis chromosomes behaved like Mendel’s elements of inheritance.

Thomas Morgan

Thomas Morgan, a fly guy as we call people that work with Drosophila these days, helped prove the Chromosome Theory of Inheritance.
Morgan was a underfunded scientist working in a tiny lab. He conducted research on a broad range of topics. Interestingly, he initially doubted the importance of Mendel’s research and Mendelian genetics.
However it was Morgan's research that proved the relationship of Drosophila sex with differences in chromosome constitution. (Figure 5.3)
Morgan not only changed his position on Mendel’s research, but he and his colleagues made startling discoveries, which firmly established that the genetic information resided on the chromosomes. Later, Morgan was a key scientist in the development of the then new science of mutagenesis.
Sex-linked inheritance was an important contribution to genetics (Figure 5.3 and 5.4a and b).
Morgan with another important scientist even developed a means to map the locations of genes to positions on chromosomes (Figure 5.5). We shall learn this method in another section.

Sex-linked Genes in Humans

Hemophilia is a sex-linked gene. (Figure 5.10)
Color Blindness is also (red-green). (Figure 5.11)
Fragile-X syndrome, the major cause of mental retardation in the United States of America, is caused by a tandem repeating unit on the X-chromosome. The repeat is more frequent in those that have the disease or those who have the potential to pass it on. (Figure 5.12)
Males are affected much more frequently by diseases caused by X-linked genes.
This is because many are recessive. Females could have another good copy of the gene to mask or cover for the defective one.
Males express what they get because they only have one copy.
If 20% of males have a sex-linked genetic disease, (.2)(.2) X 100 would be the frequency in females, or only 4%.

Genes on Human Y-Chromosome

Very few genes are on the Y-chromosome.
One codes for the famous H-Y antigen, a male specific antigen.
Another gene codes for a regulatory DNA binding protein that is involved in steering the pathways of morphogenesis toward maleness. (Figure 5.13)
There are regions of homology, meaning regions that are very similar, between X and Y-chromosomes .
Y and X do pair during meioses, also.

Sex Determination

Some species' sexual development can be influenced by the environment.
- During development, the sex sea turtles become is influenced by temperature.
- The length of daylight influences the sexual development of some plants.
- The sex of fish can be artificially influenced with the addition of steroids to their water.
There is still a genetic basis or difference, but some that are genetically female can become male and vice versa.
In humans, the genetic mechanisms for sexual differentiation have been discovered only recently.
- On the Y is a gene, TDF.
- It is found to be in the region called SRY.
- The TDF is a DNA binding protein coding gene.
- The gene product of TDF binds to sites on autosomal chromosomes to cause a sequence of gene expression in cells of the developing gonadal region that leads to testicular development instead of ovarian development. (Figure 5.15 a and b)
- After testis form, testosterone secretion influences male secondary sexual characteristics to form.

Sex Determination in Drosophila

In this species of fly, it depends on the ratio of X-chromosomes to autosomal chromosomes.

Dosage Compensation of X-linked Genes

Human females have two X-chromosomes.
Males have just one.
Dosage is adjusted in females by inactivating one of the X-chromosomes in each cell.
Early in development an X chromosome is inactivated in each cell. It might be the one from the father or the one from the mother. It is a random chance what happens in each cell. (Figure 5.21)
Once one of the X-chromosomes is inactivated in a cell, all cells from the fission of this cell have the same X inactivated.
Females are genetic mosaics in regards to genes on the X-chromosomes.
For genes that influence skin color, females can have patchy appearance.
X-chromosome inactivation requires a specific mechanism.
Recent progress has been made to elucidate the mechanism.
Two components are XIC for X inactivation center and XIST for X inactive specific transcript. XIST is actively transcribed from the otherwise inactive chromosome.
The inactive chromosome can communicate with the active. (Figure 5.22)
The inactive chromosome is more condensed and is referred to as a Barr body.
It is interesting that if an individual has three X-chromosomes, two become inactive.
Therefore, the active chromosome must be controlling the inactivation of others.