Mutation

Genetic mutations involve structural, usually transmissible change in DNA or RNA within a cell or organism. Somatic mutations affect the cells of an organism, yet are not trasmitted to the next generation unless they affect the germline, those cells, such as ova and sperm that are committed to reproduction.

Sources of variation:
¨ alternative exons ¨ Alu elements ¨ alternative splicing ¨ alternative 3' splicing ¨ alternative 5' splicing ¨ cassette exons ~ Conserved & Consensus ~ Deletion ~ Duplication ¨ epigenetic mechanisms ~ Epistasis ¨ ESE ¨ ESS ¨ exon skipping ¨ gene regulation and biological evolution ¨ genetic variation ~ Insertion ¨ intron retention ¨ ISE ¨ ISS ¨ ¨~ Inversion ~ Meiosis
~ mispairing ~ Non-disjunction ~ Recombination ~ Substitution ~ Translocation
~ Horizontal Gene Transfer ~ Conjugation ~ Transduction ~ Transformation

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

Damage to DNA can be caused by mutations such as replication errors or incorporation of mismatched nucleotides (substitution errors – transitions and transversions). DNA can suffer single or double-strand breaks (left). DNA damage can result from unintentional and intentional environmental mutagens such as oxygen radicals, hydroxyl radicals, ionizing or ultraviolet radiation, toxins, alkylating agents, and chemotherapy agents, particularly anti-cancer drugs. Cells have evolved mechanisms for repair of DNA, and all organisms, prokaryotic and eukaryotic, utilize at least three enzymatic excision-repair mechanisms: base excision repair, mismatch repair, and nucleotide excision repair.

Transmissible mutations affect the germline or result from errors during replication and cell division. Gene mutations have small-scale effects on sequences of nucleic acids, while chromosomal mutations involve larger-scale disruption of genetic material. Sequence mutations result from nucleotide alterations, insertions, deletions, or re-arrangements of gene segments, while, on a larger scale, chromosomes are altered during replication and cell division by deletion, duplication, inversion, recombination, translocation, transposition, and non-disjunction.

Depending upon their effects upon an organism within a particular environment, mutations may be neutral, beneficial, or deleterious. The commonest mutations affect single nucleotides (point mutations or SNPs). Because the genetic code is redundant, many single nucleotide substitutions are neutral. Insertion of mobile genetic elements, transposons and retrotransposons, increases genetic variability. The human genome, for example, includes approximately 500,000 Alu elements located within introns, and 25,000 of those could become new exons, coding for polypeptide sequences, by undergoing a single-point mutation.

As a result of alternative splicing, mutations that alter a splice site or a nearby regulatory sequence can have subtle effects by shifting the ratio of the resulting proteins without entirely eliminating any form. Alternative splicing also generates new polypeptide combinations from already existing code. Recently, researchers have demonstrated that modification of regulation of a single gene has enabled rapid phenotypic speciation in sticklebacks.

HHMI 30 New Mutations per Lifetime : Videos - external - Artificial Life an excerpt from the PBS series Nova Science Now - A Mutation Story on the reciprocal relationship between malaria and the sickle-cell trait - Double Immunity plague and HIV - Why Animals Mate Non-randomly: Tale of the Peacock concerning non-random mating - Sweaty T-Shirts and Human Mate Choice on pheromones - Is Love in Our DNA - poll on how we choose our mates -

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

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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