Mutations

Changes in the coding sequence of genes

Fine Structure Mutations -

• Silent Mutation

AUG.UUU.AGG.GGG.............UGG.UGA - DNA/RNA
MET.PHE.ARG.GLY..............TRP.STOP - PROTEIN:

Mutation (U to C)
AUG.UUC.AGG.GGG.............UGG.UGA
MET.PHE.ARG.GLY............TRP.STOP

• Missense

AUG.UUU.AGG.GGG.............UGG.UGA
MET.PHE.ARG.VAL............TRP.STOP

Mutation (G to A)
AUG.UUU.AAG.GGG.............UGG.UGA
MET.PHE.LYS .VAL..............TRP.STOP

• Non Sense Mutations

DNA: AUG.UUU.AGA.GGG.............UGG.UGA
PRO: MET.PHE.ARG.GLY............TRP.STOP
Mutation (A to U)
DNA: AUG.UUU.UGA.GGG.............UGG.UGA
PRO: MET.PHE.Stop

• Frame Shift Mutations

AUG.UUU.AGG.GGG.............UGG.UGA
MET.PHE.ARG.VAL............TRP.STOP
Insertion of an A
AUG.UAU.UAG.GGG.G.............UG.GUG.A
MET.TYR.STOP....
 

AUG.UUU.AGG.GGG.............UGG.UGA
MET.PHE.ARG.VAL............TRP.STOP
Deletion of a G
AUU.UUA.GGG.GG.............U.GGU.GA
ILE.LEU.GLY.GLY.... GLY.(SER,ARG?)
 

Forward Vs Reverse Mutation

• Wild type to mutant is forward.
  Red eye to white eye
• Reverse Mutation or Mutation from a mutant form to wild type is very specific. Some mutations will not back mutate because all of the information has been lost.

How many different mutations are possible within a single
codon such as UUU?

• Nonsense Suppresser Mutations
• A suppresser mutation is a reversion to original phenotype but by a mutation in another gene.
• One of the more interesting suppresser mutations is the Nonsense Suppresser Mutations.

AUG.UUU.UCA.GGG.............UGG.UGA
MET.PHE.SER.GLY............TRP.STOP
Mutation (C to A)
AUG.UUU.UAA.GGG.............UGG.UGA
MET.PHE.Stop
With a suppressor in the system
AUG.UUU.UAA.GGG.............UGG.UGA
MET.PHE.LYS.GLY............TRP.STOP
 

In E. coli a nonsense suppressor mutation will not only suppress the expression of a bacterial gene it will also suppress a viral gene.

Let us look at mutation possibilities of a nonsense codon such as UAA or "amber"

What are the amino acid coding possibilities?

Now if we assume that there is a mutant tRNA that misreads the code what would we have?

Amber

"One evening, when Bernstein was a student at Cal Tech, he went down to Seymour Benzer's lab to try to persuade his friends, Charles Steinberg and Richard Epstein, to to to the movies with him. He was unsuccessful, because Steinberg and Epstein were busy making mutant phages and could not leave. Instead, they persuaded Bernstein to make himself useful and help them. As they worked, they explained the experiments to Bernstein, who became intrigued with the project and made a prediction about its outcome. The others disagreed, so they made a bet. Whoever guessed correctly about the characteristics of the mutant phage would get to name the mutant. Bernstein guessed that it would grow on a mutant strain of E coli, but not on wild-type He proposed to name the mutant phage for his mother, Mrs. Bernstein." (Weaver and Hedrick. 1989. Genetics. P311.) The name was later translated from German to English, from "Bernstein" to "amber" which did stick.

• Ochre
• Opal - Sidney Brenner wanted to give this codon the third
  name in the color scheme but the geneticists feared a great
  string of mutants named after colors but have nothing to do with
  colors. Thus Opal is not generally accepted.

Conditional Lethal Mutations - The isolation of mutants that would grow under one condition but not another was one of the most powerful tools of genetics.

• Growth on complete medium but not on minimal was termed auxotrophic. For example, a lysine auxotroph requires MM + the amino acid lysine because it lacks one of the biosynthetic enzymes.
• Temperature Sensitive Mutants fail to grow at temperatures where wild type grow well.
  • High Temperature Sensitive mutants fail to grow at the higher range temperatures that support wild type growth. Important mutations include the DNA replication enzymes, RNA polymerase etc.
  • Low Temperature Sensitive mutants fail to grow at the lower ends of the biothermal range. Low temperature sensitive mutations seem to be limited to the ribosomal proteins in E. coli.

Mobile Elements Barbara McClintock -

Crossing over is the breakage and reunion of chromosomes - just like the sister chromatid exchange that we covered early.

Inversion of element

Excision or loss of element

Text iGenetics by Peter J. Russell

This web site is provided for instruction in Botany and Zoology 342

by Kenneth G. Wilson,
Professor of Botany
Miami University
wilsonkg@muohio.edu