BIOL 207 Lecture 5 - Mutations, Alleles, and Aberrations (Questions)

What are the two types of point mutations? What are there general effects on the strand?

Substitution: one nucleotide/base pair is affected, single nucleotide on the replicated strand

INDEL: frame shift, all nucleotides after the indel are affected

Based on the amount of purines and pyrimidines, which type of substitution mutation should be more common? Is this true in reality?

Should be more transversions (only two transitions: A to G and vice versa or G to C and vice versa)

In reality, transitions are more common

What are the factors that can cause a point mutation?

1. Spontaneous replication error: incorrect Watson-Crick base pairing causing the wrong nucleotide to be incorporated, small indel errors that may occur due to strand slippage

2. Spontaneous chemical changes: depurination, deanimation

What is the direct effect of depurination and deanimation on the affected base pair? How is this fixed/repaired?

Depurination: gap in the strand results from missing purine. Gap repaired by BER

Deanimation: a base is structurally changed to a different one (ex. cytosine → loss of amino group → becomes uracil). Foreign nucleotide recognized by BER and removes it

What is the difference between a silent and synonymous mutation?

While synonymous mutations are a type of silent mutation that occurs on the protein coding DNA regions, silent mutations also refer to a mutation in a regulatory (non-coding) DNA region.

All synonymous mutations are a silent mutation, but there are types of silent mutations that aren’t synonymous

What is a conservative and nonconservative missense mutation?

Conservative missense: substituted amino acid has similar properties to the old amino acid (ex. nonpolar for nonpolar, same size)

Nonconservative missense: substituted amino acid has different properties to the old amino acid (np → polar, size difference)

Why do we refer to the amino acid codes as “degenerate”? Why is this important to have?

Multiple codons encode a single amino acid: 64 codons for 20 amino acids. Helps to prevent mutations when replication errors occur

How do amino acid codons have “wobble room”? Which amino acids have this, and which don’t? Why?

Third position of the codon is variable in 18 amino acids

Ex. Phe can be UUU or UUC, Ser has 4 wobble codons

Trp (bulky) and Met (start) have no wobble room

Use amino acid wobble room/degeneracy to explain why transition mutations are typically less dramatic than transverse at the 3rd nucleotide of a codon.

Most amino acid wobble room is coded such that a transition mutation would be synonymous, but a transverse mutation would not

Ex. Asp is coded by GAU or GAC (3rd nucleotide transition does not change amino acid). Glu is coded by GAA or GAG (3rd nucleotide transverse of ASP changes amino acid)

What is the reading frame of a coding strand? What does an open reading frame mean?

Codons are read in 3s

Open frame: strand starts with start codon (AUG) and ends with stop

When will point mutations in non-DNA cause issues for the coded protein? Explain.

In DNA regulatory regions where inhibitor/initiator proteins bind: increases/decreases the amount of protein created

In regulatory RNA regions that are non-coding but transcribed: translation/mRNA stability is affected

In splice sites of eukaryotic mRNA (introns/exons): affects either amount of protein created or protein function

Ribosomal binding sites in bacterial mRNA: affects amount of protein created

How can SNPs be used to identify alleles linked to disorders?

Presence of certain a SNP repeatedly/commonly in patients with a specific disease allows us to find which allele the SNP is on, linking the allele to the disease

Explain how somatic and germline mutations will affect the existing/mature organism and their offspring.

Somatic:

• On the organism: if the affected cell divides, there will be a section of mutant tissue (ex. differently pigmented). The organism’s tissue is a genetic mosaic

• Offspring: most likely not affected since the gametes are not affected

Germline:

• On the organism: the individual that produces the gametes are most likely not affected

• Offspring: mutation affects all the cells of an organism derived from a mutated gamete

What determines the severity a somatic mutation (ex. pigmentation) on an individual?

Size of affected area is related to how early in development the mutation occurred. Ex. mutations during embryogenesis causes an entire body part to be affected, but a mutation closer to mature embryo may only affect one or two cells

The more the cell has to develop, the more affected area

Does cancer arise from somatic or germline mutations?

Both

Somatic: mutation occurs in an adult cell and spreads throughout the body due to rapid cell division

Germline: gamete with a mutation will grow and affect the cells in the developing embryo

Compare gene mutations to chromosomes mutations.

Gene mutation: a single gene is altered (point mutations would typically be gene mutations)

Chromosome mutation: the entire region is altered, affecting multiple genes

Classify the types of chromosome mutations via: DNA gain, DNA loss, and DNA relocation.

Gain: Duplication, extra chromosome

Loss: Deletion, missing chromosome

Relocation: Inversion, translocation