Insertion

Mutations develop from both insertion and loss of segments of DNA. Deletions or insertions of short regions can occur by strand slippage, and deletions or insertions of longer regions can occur via homologous recombination.


Diagram of insertion of a segment of chromosome a into chromosome b, resulting in shortened chromosome a' and lengthened chromosome b' (click to enlarge image).

If the number of inserted bases is not a multiple of 3, insertion will cause frameshift, with serious consequences. A number of diseases are caused by insertions without frameshift - Huntington's chorea, Myotonic Dystrophy, Fragile X site A, Fragile X site E, Fragile X site F, Kennedy disease, SCA1, DRPLA.

Proteins gradually evolve by the accumulation of mutations.

Mobile elements called insertion sequences exist in nature. These sequences encode only the information necessary for their insertion into DNA. Depending upon the particular insertion sequence, they can insert at specific regions or at random.

Tables  Mechanisms of Biological Evolution  Gene Regulation in E.coli :

It has been known since the beginning of the twentieth century that unstable or variable gene loci occur in plants. Breakage-fusion (reunion)-bridges are formed during anaphase whenever two chromosomes fuse at their ends, generating a fusion product with two centromers. If these two fused chromosomes are subsequently carried to different poles than the regular chromosomes, a chromosomal fraction results. During the subsequent S-phase, the chromatid with a fused-fraction at its terminus will replicate, leading again to a fusion of the homologous chromatids. Consequently a chromosome comprising one chromatid with two centromeres will occur in the subsequent mitosis, rather than a chromosome from two chromatids and one centromere. Consequently, a second fraction occurs during anaphase when the second round of the cycle starts.

B. McClintock recognized (between ‘47 and ‘51) that the chromosomal fraction is restricted to certain sections of the chromosome, which she termed Ds (dissociation). The Ds segment is a mutator gene, which behaves like a pseudoallele that can be located at different gene loci. This mutator gene can insert itself into other genes, rendering them inactive. Thus, it is a control element that changes its location within the chromosome, causing mutations wherever it inserts. Such mutator genes are also called "jumping genes".

A further set of elements, the Ac (activation) elements, support the chromosomal fraction or a translocation of a Ds element. An Ac element can be regarded as a multiple allele, and it may occur different sites in all chromosomes. A number of gene loci are known to be influenced by the Ds-Ac-system or other control elements. Detection of the spm-system (suppressor-mutator) and the elucidation of its function established that the control elements not only act as switches (a yes/ no decision) but that they also modulate the degree of gene expression.

Insertion elements and transposons were first detected in bacterial DNA during the late sixties. This discovery explained the connection between transposons and the chromosome fraction control elements.

 Table Mechanisms of Biological Evolution :  Gene Regulation in E.coli :

External : Transposons part 1, transposons part 2 : Barbara McClintock and mobile genetic elements :

| 2 Guide-Glossary

Where 'Jumping Genes' Fear To Tread

Where 'Jumping Genes' Fear To Tread: "Scientists from the University of Queensland report in the journal Genome Research that large segments of the human genome are conspicuously devoid of ubiquitous mobile DNA elements called transposons. The locations of these regions are highly conserved among mammalian species and are enriched in genes crucial for the regulation of developmental processes.

Transposons, often called "jumping genes," are DNA sequences that have the capacity to move from one chromosomal site to another. More than three million copies of transposons have accumulated in humans throughout the course of evolution and now comprise an estimated 45% of the total DNA content in the human genome.

These mobile genetic elements are scattered throughout the human genome -- separated, on average, by only 500 base pairs. But Dr. John Mattick's laboratory at the University of Queensland, Australia, identified long tracks of genomic segments (greater than 10 kilobases in length) that lack transposable elements. His team identified 860 such sequences in humans, 993 in mice, and 559 in opossums. They named these segments TFRs, or transposon-free regions.

"Strikingly," says Mattick, "many TFRs in the human genome occur in the same position in the mouse and opossum genomes, despite the fact that transposons entered each lineage independently, after each species diverged from a common ancestor. It appears that many TFRs are evolutionarily conserved features that existed prior to -- and have been largely maintained since -- the divergence of eutherian mammals and marsupials approximately 170 million years ago."

The opossum was chosen for inclusion in the analysis because it is a marsupial that has a similar load of transposable elements compared to mice and humans but is evolutionarily distant from the two species. In contrast, the genomes of chicken and fish, which diverged from humans more than 300 million years ago, do not have a significant density of transposons.

Given the strong evolutionary conservation of the TFRs, Mattick's group hypothesized that they are regions of significant biological importance. Upon further characterizing the TFRs, they discovered that many (85%) overlapped at least one annotated gene and that almost all (94%) overlapped at least one known RNA transcript. In addition, the TFRs were enriched in microRNAs, in genes that encode proteins with putative DNA-binding activity, and in genes that are involved in developmental processes. Another striking feature of TFRs was that they are associated with ultra-conserved regions, or genomic segments longer than 200 base pairs with 100% identity between human, mouse, and rat. All of these observations strongly support an important role for TFRs in critical biological processes.

"The majority of the TFRs lie outside of protein-coding sequences, so they presumably represent regions of regulatory information or RNA transcripts that cannot be disrupted. However, it's difficult to explain mechanistically the requirement of 10 or more kilobases of uninterrupted sequence in terms of the current paradigms of transcriptional regulation," explains Mattick. "It appears that TFRs might be the passive signatures of one or more poorly understood mechanisms of gene regulation that operate in higher organisms, suggesting a wider role for noncoding sequences than has hitherto been appreciated." "

External : Transposons part 1, transposons part 2 : Barbara McClintock and mobile genetic elements :

| 0 Guide-Glossary