Mutations In molecular biology and genetics, mutations are changes in the DNA sequence of a cell's genome. ntent/variation/

Example: Melanin gene = pigment protein skin, hair, eye color Genotype: the genetic makeup of an individual TACAATCCTCGTTGCTAC TACAACCCTCGTTGCTAC Phenotype: physical appearance of a trait (ex: fur color)

Positive? Negative? Neutral? Why? 1. Mutations occur randomly 2. These cause constant variation in traits 3. Natural selection occurs

Peppered Moths (Biston betularia)

Everyone acquires some changes to their DNA during the course of their lives. These changes occur in a number of ways. Sometimes there are simple copying errors that are introduced when DNA replicates itself - every time a cell divides, all of its DNA is duplicated so that the each of the two resulting cells have a full set of DNA. Other changes are introduced as a result of DNA damage through environmental agents including sunlight, cigarette smoke, and radiation. Any physical or chemical agent that changes the genetic material, increasing the rate of mutations is called a MUTAGEN. Some mutagens can also be carcinogens – cancer causing agents, or teratogens – cause birth defects in fetus.. teratogens Our cells have built in mechanisms that catch and repair most of the changes that occur during DNA replication or from environmental damage. As we age, however, our DNA repair does not work as effectively and we accumulate changes in our DNA.

Some of these changes occur in cells of the body (“somatic” cells) — such as in skin cells as a result of sun exposure — but are not passed on to children. But other errors can occur in the DNA of cells that produce the eggs and sperm. These are called germline mutations and can be passed from parent to child. If a child inherits a germline mutation from their parents, every cell in their body will have this error in their DNA. Germline mutations are what cause diseases to run in families, and are responsible for hereditary diseases.

So, what’s the deal? A gene is essentially a sentence made up of the bases A, T, G, and C that describes how to make a protein. Any changes to those instructions can alter the gene's meaning and change the protein that is made, or how or when a cell makes that protein.

How does it work? There are many different ways to alter a gene, just as there are many different ways to introduce typos into a sentence. In the following examples of some types of mutations, we use the sentence to represent the sample gene: THE FAT CAT ATE THE RAT (this is how the code should read) Here’s a handy table listing all the types of mutations:

Point mutation: a change in a single nucleotide Example 1: A SUBSTITUTION mutation occurs where one nucleotide base is replaced by another. ◦ example  THE FAT CAT ATE THE RAT  THE FAT HAT ATE THE RAT

Point mutations: types Base (A,T,C,G) substitutions can lead to “Missense” or “Nonsense” mutations: Missense: a change in DNA sequence that changes the codon to a different amino acid. This can alter the protein enough to render it nonfunctional. Not all missense mutations are deleterious, some changes can have no effect. Because of the ambiguity of missense mutations, it is often difficult to interpret the consequences. Nonsense: a change in the genetic code that results in the coding for a stop codon rather than an amino acid. The shortened protein is generally non-function or its function is impeded.

Point mutations can sometimes be “SILENT”. How does this change the protein that this gene codes for? More often than not, “third-base mutations” are silent. Why? Another example: Amino acid: leucine GAA GAG GAT GAC

Sickle Cell Anemia Is an inherited blood disorder than is caused by a substitution point mutation in the hemoglobin gene. This is an example of a ____?____ mutation. Look at the effect of abnormally-made hemoglobin in red blood cells:

Point mutation: a change in a single nucleotide in a gene Examples 2 & 3: ◦ Insertion example  THE FAT CAT ATE THE RAT (original gene)  THE FAT CAT LAT ETH ERA T ◦ Deletion example  THE FAT CAT ATE THE RAT (original gene)  THE FAT ATA TET HER AT These substitutions are known as “Frameshift Mutations” because they shift the reading frame of the genetic message (triplets) so that the protein may not be able to perform its function. Usually more serious than a substitution mutation. Why?

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Remember: not all mutations are bad! A harmful mutation is a mutation that decreases the fitness of the organism. Sometimes, mutations can change a gene form in a nonharmful, or even beneficial, way. “Polymorphisms”: slight variations in a gene sequence that make us different, ex: eye colors, blood types, etc. Are these good or bad? A mutation may enable the mutant organism to withstand particular environmental stresses better than non- mutant organisms, or reproduce more quickly. In these cases a mutation will tend to become more common in a population through natural selection. This is how populations EVOLVE over time.natural selection

Many mutations are neutral A neutral mutation has no harmful or beneficial effect on the organism. Many of these mutations occur in the noncoding DNA describes components of an organism's DNA sequences that do not encode for protein sequences. More than 98% of the human genome does not encode protein sequences. We often call this “junk DNA” (extra).

Chromosome Mutations A chromosome mutation is an unpredictable change that occurs in a chromosome. These changes are most often brought on by problems that occur during meiosis (cell division that makes gametes) or by mutagens (chemicals, radiation, etc.). Chromosome mutations can result in changes in the number of chromosomes in a cell or changes in the structure of a chromosome. Usually MUCH more serious than a gene mutation. Why?

Changes in chromosome number or structure A B CD E FG H Deletion A B C E G H F A B CD E FG H Duplication A B C B D E C F G H A A MN OPQR B CD EFGH B CDEFGH Inversion Reciprocal translocation A BPQ R M NOCDEF G H A D CBEFH G (a)A deletion removes a chromosomal segment. (b)A duplication repeats a segment. (c)An inversion reverses a segment within a chromosome. d)A translocation moves a segment from one chromosome to another, nonhomologous one. In a reciprocal translocation, the most common type, nonhomologous chromosomes exchange fragments. Nonreciprocal translocations also occur, in which a chromosome transfers a fragment without receiving a fragment in return. 18

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Changes in Chromosomal Structure (animation) hill.com/sites/ /student_view0/chapter24/chang es_in_chromosome_structure.html hill.com/sites/ /student_view0/chapter24/chang es_in_chromosome_structure.html The Consequence of Inversion (animation) hill.com/olcweb/cgi/pluginpop.cgi?it=swf::535::535::/sites/dl/ free/ /120082/bio33.swf::The%20Consequence %20of%20Inversion hill.com/olcweb/cgi/pluginpop.cgi?it=swf::535::535::/sites/dl/ free/ /120082/bio33.swf::The%20Consequence %20of%20Inversion