MUTATION

Mutations Definition: Mutations are changes made to the nucleotide sequence of the genetic material in a cell. ERROR  Textbook says mutations are changes to the DNA sequence that are inherited. DON’T HAVE TO BE INHERITED

Are all Mutations Bad? Nope. Most mutations have no affect whatsoever because they’re either in non-coding regions, not expressed or don’t affect the structure of proteins.

Good Mutations Some mutations improve proteins making them better. The passing on of improved DNA is the basis of evolutionary biology.

Mutation and CANCER Cancer - disease where a group of cells display uncontrolled division, invasion and destruction of adjacent tissues, and sometimes metastasis (moving to new areas via blood or lymph system)

Causes of CANCER Cancer is caused when mutations create oncogenes (cancer genes that allow for really fast cell growth and division) and deactivate tumour suppressing genes. Its very rare for all these required mutations to occur together and cause cancer

Substitutions The replacement of one base in a DNA sequence by another base. (Causes either silent missense, or nonsense mutations) e.g.. ATCCAGGTCTC goes to ATGCAGGGCTC

Substitutions can also be referred to as Point Mutations Point Mutation are mutations at a specific base pair in the genome.

Silent Mutations Substitutions that do not result in a change in the amino acid coded for by the codon. Can also be point mutations, or any type of mutation in a non- coding region

Silent Mutations E.g.// Silent Point Mutation TAC TTC GAG GCG AUG AAG CUC CGC Met Lys Leu Arg TAC TTC GAT GCG AUG AAG CUA CGC Met Lys Leu Arg No change because both CUC and CUA code for Leucine

Missense Mutation Substitution that results in a different AA being coded for by a codon. Is sometimes bad for cell. E.g. Sickle Cell Anaemia

Nonsense Mutation Substitution that causes a protein coding codon to become a stop codon ***often lethal to the cell

Frame shift Mutation Any mutation that causes the reading frame of codons to change. Can be caused by insertions, deletions, translocations, and transposable elements

INDELS Insertions and Deletions Insertions: ATGCCAT  ATGAGGCCCAT Deletions: ATGGCACTGTGCA  ATGCA Indels can involve the removal or addition of 1 or thousands of bases

Insertions: the placement of 1 or more extra nucleotides into a DNA sequence Deletions: the removal of 1 or more nucleotides from a DNA sequence. INDELS

Translocations The transfer of a fragment of DNA from one site in the genome to another. E.g.: ATCGCGCTTGCT  ATTTGCGCGCCT

Translocations Translocation can occur on much larger scales:

Transposable Elements Long segments of DNA that can sometimes contains genes which get “copied and pasted” or “cut and pasted” (translocation) throughout genome

Inversion The reversal of a segment of DNA within a chromosome. E.g.: ATGCTTGCATACAC To ATGTACGTTCACAC Good Test Question: Which type of mutation can change many bases and never causes a frameshift mutation? --Inversions

Causes of Mutations Spontaneous Mutations – caused by accidental errors made by genetic machinery of the cell Induced Mutations – mutations caused by a chemical agent, virus, or radiation

RADIATION

Example of Direct Effect: Tanning UV rays from sunlight cause mutations as well as a killer tan

Example: Tanning UV rays create thymine dimers

Example: Tanning Thousands of TT dimers are formed each second in skin cells while we tan. We repair 99.99% of these dimers, but sometimes they cause bases to change or move places.

X-Rays X-rays are powerful enough to break bonds in the DNA backbone. This sometimes causes mutation

Chemical Induced Mutations Chemicals react with DNA either directly or indirectly which sometimes causes base pairs to change. E.g.// 10% of the Oxygen we breath doesn’t scoop up electrons from ETC, but rips electrons off random molecules in cells creating radicals which can then react with DNA potentially causing mutations

Ethanol Increases risk of getting a number of cancers.

E.g./ Bisphenol-A Bisphenol-A may cause cancer if you boil your beverage in a Nalgene for 120 hours before drinking

Viruses Some viruses activate Oncogenes so the cells they infect work faster and multiply to produce new viruses faster

Virus Induced Mutation E.g.// HPV – popular in media due to Guardasil vaccine. Causes cervical cancer. Also causes throat cancer. If you chew tobacco or smoke you’re 3-4 times more likely to get throat cancer. If you have throat HPV you’re times more likely to get throat cancer.