Duplications and Deletions
Human Diseases Related to Altered Chromosome Structure
Duplications and Deletions
A mechanisms that could generate a duplication is multiple replication of a looped region of DNA by DNA polymerase. That individual would have one chromosome with an extra copy of the sequence whereas the homologous chromosome would still retain a single copy of the sequence.A second proposed molecular mechanism that can generate a duplication of a chromosome by its very nature will also generate a deletion. This mechanism is unequal crossing-over. This occurs when pairing occurs between homologous chromosomes in regions that are out of register. This pairing can be mediated by sequences that are repeated on the same chromosome. Following recombination (or crossing over) one chromosome will lose DNA sequence whereas the homologous chromosome will gain the sequences lost by the first.
The presence, and extent of a deletion, can be detected quite readily with polytene chromosomes. A loop will appear on one paired chromosome, and those sequences found in the looped region mark the length of the deletion. These loops are also detectable in other species. Analysis of heterozygote chromosomes during pairing will also reveal a loop structure, but without the band markers that are available with polytene chromosomes, it is difficult to define the region. Obviously, it will be to be easier to detect the larger deletions, but with good preparation and patience, the deletion of a single band can be detected, and thus the chromosomal location of a specific phenotype can be made.
Evolution and Unequal Crossing Over
One possible result of unequal crossing-over is the creation of a multigene family. These are defined as a tandem array of genes that have similar function. The best studied family is that which encodes the *-chain of human hemoglobin. Six * -globin genes are found within 50 kb on chromosome 11. The * gene is expressed during early embryo development, the two * genes during fetal development, the * gene early after birth, and the * gene throughout the remainder of the life cycle. The **1 gene is a pseudogene that has a mutation which prevents its expression. The sequences of these six genes are quite similar which suggests they occurred by duplication of an ancestral *-globin gene.Once a gene duplication event has occurred evolutionary constraints working upon these gene presumably lessen. First, another unequal crossing-over event could generate a third copy of the gene, further expanding the family. Other similar events will further spread the family. As the family expands, previous harmful mutations can now be tolerated because functional copies will still exist. Duplicate genes could now diversify and take on new or more specialized functions. Thus, over evolutionary time the sequences of the family members can diverge, and their role in phenotypic expression of the individual could change.
Deletions and duplications involve an actual gain or loss of genetic material by the genome of the specific individual. If these changes are maintained and prove to beneficial then eventually these changes might become stabilized in the species.
Duplications of the Bar locus of Drosophila
One phenotype that has been analyzed in Drosophila with respect to duplications is bar eye. The eye of the fly is normally an elongated oval shape whereas the bar eye phenotype is much thinner. When the chromosomes of males with bar eye are analyzed, a duplication in region 16A of the chromosome is detected. Another mutant of the eye shape is the double bar eye. These individuals have a second duplication of the same 16A region.This example shows how Drosophila polytene chromosomes can be used. First, a new phenotype is detected and after further analysis of these endoreplicated chromosomes the actual location of the sequences encoding the phenotype can be detected. Likewise, if a deletion is noted in an individual with a specific phenotype, it could be assumed that the deleted region is the gene involved with phenotype.
| Chromosome Structure | Phenotype |
|---|---|
| X-16A X-16A |
Normal Eye Female |
| X-16A-16A X-16A |
Bar Eye Female |
| X-16A-16A X-16A-16A |
Bar eye female (more restricted, 68 facets) |
| X-16A-16A-16A X-16A |
Double bar eye female (45 facets) |
| X-16A-16A-16A X-16A-16A-16A |
Double bar eye female (further reduced) |
The results of the analysis of the Bar locus demonstrates that the chromosomal environment can have an effect on the expression of a specific gene. The term used to describe this phenomenom is position effect.
Position effect - the phenotype of a gene is alteredd by changes in the position or chromosomal environment of the gene
Copyright © 1997. Phillip McClean