What is the Role of the Chromosome in Inheritance?

Objectives

By the end of this lesson you should be able to:

1. Describe how Thomas Morgan made the discovery that some genes are X-linked
2. Explain your understanding of Barr body
3. Use your understanding of Barr body to explain how tortoiseshell cats get their color
4. Explain how Thomas Morgan was able to make the conclusion that genes in his experiment was not sorting independently but appeared to be linked  

Thomas Morgan and His Discovery of X-linked Genes

Mendel attributed phenotypes to “heritable factors” but did not know what those heritable factors were. Today we know that these heritable factors are genes. It was Thomas Hunt Morgan, an experimental embryologist at Colombia University who first recognized that Mendel’s heritable factors are located on chromosomes. Morgan worked with fruit fly, Drosophila melanogaster. Working with fruit flies offers some advantages. For example,

1. They produce hundreds of offspring in a short time allowing them to be bred every 2 weeks
2. They have only 4 chromosome pairs which are easily distinguishable under light microscope

Morgan discovered that the white-eye trait in the flies was associated with gender. He made this conclusion by running an experiment where he mated wild type fruit flies having red eyes (w+) with mutant males having white eyes (w). This produced F1 offspring that were all of the wild type. This meant that the gene for red eyes was dominant. He then took the F1 offspring and mated them together. This resulted in offspring type characterized by 3 red-eyed flies to 1 white eyed fly. He noticed that females were always red-eyed. This led Morgan to conclude that the trait for eye color was located on the X chromosome.

Several diseases are now understood to be the cause of X-linked genes. These include hemophilia, red-green color blindness, Duchenne muscular dystrophy and fragile X syndrome. The defective gene could be either on the X or Y chromosome.

Barr Body

You might think that male mammals are at a disadvantage in having less sex genes than females. Actually, males and females have the same effective dose (one copy) of most of the X-linked genes. This is due to inactivation of most of one of the X chromosome genes in females. The inactive X in each cell of a female condenses into a compact object lying along the periphery of the nuclear envelope called the Barr body. The inactive Barr body chromosomes get reactivated in cells that gives rise to eggs so that each female gamete has an active X chromosome. The selection of which X chromosome will form the Barr body occurs randomly and independently in each embryonic cell. Mitotic descendants of a cell with inactivated X chromosome will have the same inactive X chromosome.

X chromosome inactivation explains the appearance of the tortoiseshell cat. Female cats that are heterozygous with alleles for black and orange fur will be able to express both colors. This is because they will have populations of cells in which the black allele is active and population of cells where the orange fur is active.

Linked Genes

We saw earlier that Morgan discovered that some phenotypes are influenced by sex. He also discovered that certain genes are inherited together since they are close together on the chromosome. He found out by mating true-breeding wild-type fruit flies having gray body and normal wings (b⁺b⁺vg⁺vg⁺) with true-breeding mutant flies having vestigial wings and black body (b⁺b⁺vg⁺vg⁺). This produced an F1 generation that all had gray body and normal wings (b⁺bvg⁺vg).

When the F1 generation females were crossed with the male parent type (bbvgvg) he noticed he did not see the typical 1:1:1:1 phenotype ratio that you would expect from chromosome independent assortment and segregation.   

Instead what he observed was mostly the parental phenotype (1:1:0:0 ratio).

This led Morgan to conclude that the genes for body color and wing type were inherited together rather than being randomly assorted independently. It was hypothesized and shown that this happened because genes were close together. The closer genes are on the chromosome, the greater the chance that they will stay together rather than get separated during meiosis.

So, in his experiment if a fly had gray body, it generally had normal wings. Also, if a fly had a black body, then it should normally have vestigial wings. Simply, if you see one, you see the other. The alleles are not crossing over but are staying together.

However, Morgan did observe some recombination, i.e., black body with normal wings (bbvg⁺vg) and gray body with vestigial wings (b⁺bvgvg). This crossing over, or recombination occurs during prophase I of meiosis I.

Figure 3. Possible gametes if genes are linked or unlinked

There is a 50% chance of recombination for any two genes that are located on different chromosomes i.e. 50% chance that they recombine and 50% chance that they don’t. A recombination of more than 50% indicate that the genes are linked.

The distance between genes can be estimated based on the frequency of recombination. The higher the recombination frequency, the further apart the genes are. That is, genes that are further apart are more likely to recombined compared to ones that are closer. Remember that genes that are closer tend to stay together on the same chromosome and are inherited together.  A gene map based on recombination frequency is called a linkage map. The distance between genes on the chromosome is referred to as map units. One map unit is equivalent to 1% recombination frequency.

Genetic Diseases Due to Alteration of Chromosome Number

Earlier, I mentioned some diseases that are caused by defective genes located on the X or Y chromosome. What else could go wrong with the chromosome? Some genetic diseases can be the result of having an altered number of chromosomes. This occurs when the spindle fails to distribute chromosomes to the daughter cells evenly. This problem is called a nondisjunction. It can happen when the chromosomes do not separate evenly during Meiosis 1 or when the chromatids do not separate evenly during Meiosis II.

When the aberrant gamete unites with a normal gamete at fertilization, the zygote will also have an abnormal number of chromosomes. We call this condition aneuploidy. If the aneuploid has only one chromosome, it is called monosomy, and if there are three it is called trisomy. A trisomy at chromosome number 21 causes down syndrome.

A condition known as polyploidy occurs when the number of chromosomes set increases. This is different from the one deletion or addition that we see in aneuploidy.    

Polyploidy is more common in plants where it often produce beneficial effects. Examples of polypoid plants include:

1. Wheat – hexaploidy
2. Potatoes – tetraploid
3. Strawberry – octoploid
4. Bananas – triploid

Alterations in Chromosome Structure

Diseases can be caused not only by alteration in chromosome number but also by chromosome damage. Damage to the chromosome usually occurs due to errors in meiosis or exposure to damaging agents such as radiation and chemicals. Four types of structural errors are common. These include:

1. Deletion: Removal of a chromosomal segment
2. Duplication: Repeating of a chromosomal segment
3. Inversion: Reversal of a segment of chromosome, e.g. A-B-C sequence switched to C-B-A.
4. Translocation: A piece of chromosome breaks off and attaches to another chromosome   

Inheritance Patterns that Do Not Follow Mendelian Genetics

Genomic Imprinting

In Mendelian genetics, a phenotype is acquired based on the allele present, regardless of whether or not it is coming from the father or mother. Contrary to this, some traits are expressed depending on which parent it came from. This is called genomic imprinting. Most imprinted genes are on autosomes. Methylation of the cytosine nucleotide of one of the alleles (i.e., from mother or father) is found to be the mechanism at work. Embryo engineering experiments to unsilenced one of the alleles to make them both active, resulted in death of the organism before birth.

Inheritance of Organelle Genes

So far, we have talked only about genes located on the chromosome in the nucleus. However, there are also extranuclear genes found in the cytoplasm e.g. mitochondria and chloroplast genes. These genes are not distributed to offspring according to the rules of meiosis. They are inherited mainly from the female parent via the cytoplasm of the egg. The egg is the main contributor of plastids due to its large size relative to the sperm. Extranuclear genes code for proteins that affect cell metabolism.

Textbook: Textbook: Reece, J. B., & Campbell, N. A. (2011). Campbell biology. Boston: Benjamin Cummings / Pearson.