GENE MUTATIONS Introduction Every normal cell carries a

GENE MUTATIONS

Introduction Every normal cell carries a full complement of genetic material n A mutation can occur in: n ¨a somatic (body) cell ¨ a germinal (reproductive) cell – can be transmitted to offspring

Introduction Split this into codons! Thesunwashotbuttheoldmandidnotgethishat. n It should look like this. . . The sun was hot but the old man did not get his hat. n What if we added another T at the beginning? T hes unw ash otb utt heo ldm and idn otg eth ish at. n

Mutations. . . not all are bad! n n n mutations are random changes in genetic material rare events most mutations that are detectable are detrimental some mutations provide variation, allowing for adaptation to the environment (can be favorable) some mutations cannot be detected

Types of Mutations

Silent mutation: ¨ does not result in a change in the amino acid sequence of the protein, ¨ due to the redundancy of the genetic code ¨ or a change in the code on the introns. Eg: The A. A. Phe is coded for by UUU and UUC… if U gets swapped for C on the m. RNA strand the mutation will have no effect. Phe will still be coded for!

Missense mutation: ¨a mutation that results in the single substitution of one amino acid in the protein. ¨ E g. sickle cell anemia. ¨ Only affects one base pair on the DNA or one codon of m. RNA. ¨ Can be called a base pair substitution in this case.

Sickle Cell Anaemia Sickle cell anemia Image Credit: http: //explore. ecb. org/videos/VLC_media? P 1=VLC 0 92&REFERER=OTHER Blood smear (normal) Image Credit: http: //lifesci. rutgers. edu/~babiarz/

Nonsense mutation: ¨a mutation that converts a codon for an amino acid into a stop codon (usually lethal to the cell). ¨ Also called a chain termination mutation. ¨ AAC – Codes for Asn but if changed to UAA it is now a stop codon ¨ UGA, UAA and UAG are the stop codons!

Frame shift mutation: ¨ occurs when the reading frame is changed. ¨ Base pair deletion (one is missing) or base pair insertion (one is added). ¨ Changes the remainder of the code.

Point Mutation: The previous examples are point mutations. n They involve one base pair! n http: //www. youtube. com/watch? v=kp 0 esid Dr-c&feature=related n

Chromosomal mutation: ¨ shape change or missing piece of chromosome; ¨ can result in inactivation of the entire gene

Translocation mutation: ¨ occurs when groups of base pairs are relocated from one area of the genome to another, ¨ usually between two nonhomologous chromosomes. ¨ Results in a fusion protein (two unrelated gene sequences being transcribed together)

Inversion: ¨ chromosomal segment reverses its orientation. ¨ Gene control is affected. n AUG UUU UUG CCU n UCC UUG UUU GUA

Some examples!!! DNA m. RNA Polypeptide Normal gene GGTCTCCTCACGCCA ↓ CCAGAGGAGUGCGGU Codons ↓ Pro-Glu-Cys-Gly Amino acids

Mutations: Additions Addition: TAG CAT GAG becomes TTA GCA TGA G

Mutations: Additions A frame shift mutation Normal gene GGTCTCCTCACGCCA ↓ CCAGAGGAGUGCGGU Codons ↓ Pro-Glu-Cys-Gly Amino acids © 2010 Paul Billiet ODWS Addition mutation GGTGCTCCTCACGCCA ↓ CCACGAGGAGUGCGGU ↓ Pro-Arg-Gly-Val-Arg

Mutations: Deletions Deletion: TAG CAT GAG Becomes TGC ATG AG A

Mutations: Deletions A frame shift mutation Normal gene GGTCTCCTCACGCCA ↓ CCAGAGGAGUGCGGU Codons ↓ Pro-Glu-Cys-Gly Amino acids © 2010 Paul Billiet ODWS Deletion mutation GGTC/CCTCACGCCA ↓ CCAGGGAGUGCGGU ↓ Pro-Gly-Ser-Ala-Val

Mutations: Substitutions Substitution: TAG CAT GAG Becomes TCG CAT GAG Similar Pro with one different A. A

Mutations: Substitutions Normal gene GGTCTCCTCACGCCA ↓ CCAGAGGAGUGCGGU Codons ↓ Pro-Glu-Cys-Gly Amino acids Substitution mutation GGTCACCTCACGCCA ↓ CCAGUGGAGUGCGGU ↓ Pro-Arg-Glu-Cys-Gly Substitutions will only affect a single codon Their effects may not be serious unless they affect an amino acid that is essential for the structure and function of the finished protein molecule (e. g. sickle cell anaemia)

The genetic code is degenerate A mutation to have no effect on the phenotype Changes in the third base of a codon often have no effect. © 2010 Paul Billiet ODWS

No change Normal gene GGTCTCCTCACGCCA ↓ CCAGAGGAGUGCGGU Codons ↓ Pro-Glu-Cys-Gly Amino acids © 2010 Paul Billiet ODWS Substitution mutation GGTCTTCTCACGCCA ↓ CCAGAAGAGUGCGGU ↓ Pro-Glu-Cys-Gly

Disaster Normal gene GGTCTCCTCACGCCA ↓ CCAGAGGAGUGCGGU Codons ↓ Pro-Glu-Cys-Gly Amino acids © 2010 Paul Billiet ODWS Substitution mutation GGTCTCCTCACTCCA ↓ CCAGAAGAGUGAGGU ↓ Pro-Glu-STOP

What Causes Mutations? n Spontaneous mutations ¨ occur under normal conditions. ¨ May involve mispairing during replication n Induced mutation ¨ caused by mutagenic agents – chemical agent or radiation ¨ Examples: (X-rays, formaldehyde, toluene, UV…)

Page 263. . . great summary chart n Do Q 1 -4, 6 n A great site for review! n http: //learn. genetics. utah. edu n