Mutations and Genetic Exchange

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Presentation transcript:

Mutations and Genetic Exchange Scope of Mutations Mutation Types Mutation Causes Genetic Exchange via Recombination Transformation Conjugation Transduction Transposable Elements

Scope of Mutation: A mutation is any change in the proper nucleic acid sequence of a specific gene in a cell’s genome. It may result from a single base pair mismatch during DNA replication. Mutation can create genetic diversity within a population; either beneficial, neutral, bad, or lethal. Mutation could result in a new phenotype that is advantageous to successful reproduction of the mutated individual; this depends on particular environmental conditions, called selective pressures. Such beneficial mutations stay within a population from generation to generation, and drive the evolution of that species. Bad or lethal mutations are often lost from a population over subsequent generations.

A single base substitution will change a codon; a new amino acid in the gene’s protein product may result. Spontaneous Mutation:

E.g., Human Sickle Cell Anemia Why does this stay in human populations? Africans with one good and one mutated gene are resistant to African Sleeping Sickness, a lethal infections disease.

Base Substitutions: NORMAL: 1) NUETRAL: 2) MISSENSE: 3) NONSENSE:

Frameshift Mutation: NORMAL: Results from 1 or 2 base deletion or addition to the DNA. Causes the “reading frame” of codons to change. All codons read down from a frameshift may change every amino acid during translation. Think of a simple sentence of 3-letter words” e.g. “The cat eat the fat rat.” Now, “The ate att hef atr at” DELETION:

Chemical Mutagens: Base Modification Nitric Acid (nitrite ion) reacts with amine groups to form nitrosamines in adenine. This base modification causes adenine to act like guanine.

Chemical Mutagens: Base Analogs Base analogs mimic the critical chemical form of a normal base, so it gets incorporated during DNA replication. However, its proper base pairing function is altered so subsequent generations will maintain the mutation.

UV Light Mutation Thymine dimers can be repaired by a few different mechanism in the cells. One important repair system for thymine dimers and chemical mutations is “excision repair”. Excision repair involves cutting out the bad sequence on the mutated strand and replacing it with the proper bases. The goal is to make repairs in DNA before it is replicated for the next generations, as that would pass on mutations.

Excision Repair: However, high UV doses may cause accumulation of too many thymine dimers for their repair prior to DNA replication. DNA replication is interrupted. Rather than stop replication all together – certainly lethal - the DNA Polymerase is forced to randomly add bases. This “error prone” repair represents a last chance for survival. Another name for this is “SOS repair”.

Genetic Recombination: Two DNA molecules may recombine segments of their molecule in a process called crossing over. This is a relatively common event between chromosome copies in eukaryotes during meiosis. (Note the example here.) Prokaryote chromosomes, viral DNA, and smaller fragments of “foreign” DNA may recombine, adding new genes (or different alleles) to an individual cell. Bacteria can receive a foreign source of DNA for recombination through one of three different mechanisms of Genetic Exchange: Transformation (external fragment) Conjugation (bacterial “sex”) Transduction (viral mediated)

Transformation: 1) Foreign DNA from a dead donor cell is released into the environment as fragments. 2) Fragments can be taken up by a recipient cell. 3) A portion of foreign DNA may there recombine with recipient’s chromosome. Recipient cells have been transformed into a new genotype. Non-recombined foreign DNA eventually gets degraded by recipient cell nucleases. A process that is performed naturally by some bacteria, or may be forced artificially in the laboratory.

Conjugation: Live donor contains an special fertility plasmid (F factor) that allows it to mate a recipient cell without an F factor and transfer a copy of the F factor into the recipient. This is referred to as a “F+ x F- mating” and results in both cells being F+. 1) The F+ cell produces a sex pilus that will only attach to F- cell. 2) Once attached, the F factor’s DNA is replicated by rolling circle replication. 3) A linear copy of F factor is transferred via the pilus into the recipient. 4) F factor DNA circularizes in recipient and the pilus detaches.

F+ → Hfr A small percentage of donor cells with an F factor will have that DNA recombine into the donor cell’s chromosome DNA at a specific site. F+ cells that have their F factor integrated into their chromosome are called high frequency of recombination (Hfr) cells. Like F+ cells, Hfr cells can produce a pilus and mate with an F- cell.

Htr x F- mating Once the pilus has attached, again the DNA from the F factor begins rolling circle replication to transfer DNA across the pilus into the recipient. However, only the initial portion of F factor DNA gets copied and transferred, the remaining majority of what is copied and transferred is chromosomal DNA from the donor cell. Only a fragment of the donor chromosome transfers. Recombination between the recipient’s chromosome and the transferred donor chromosome fragment happens at a very high frequency. The recombinant F- cell is called a F’ cell, which now has new genes and/or alleles.

Transduction: Viruses are involved in genetic exchange called transduction. Viruses are not cellular life; we simply refer to them as a particle, or virion. Specifically, viruses of bacterial cells are called bacteriophage. The bacterial cell is the host. Bacteriophage have an outer protein coating called a capsid and inside resides its small genome (phage DNA) Viral infection will eventually result in controlling the host cell’s “machinary” to replicates hundreds of new viral particles. Sometimes, although rare, host (donor) DNA gets packaged into capsid proteins, forming what is called a tranducing particle. Transducing particles can infect other bacteria (recipient), where the donor DNA fragment can recombine with the recipient chromosome.

Transposable Elements: “Jumping Genes” Transposable elements (insertion sequences and transposons) can tranfer copies of themselves to other DNA molecules (chromosome, plasmid, or viral DNA). Antibiotic resistance genes rapidly spread within and between bacterial populations by transposons carried on F factors called R plasmids.