Lecture 7 Mutation and Genetic Variation

gene

fundamental unit of heredity, often codes for proteins

locus

specific place on the chromosome where a gene is located (physical location)

allele

variant forms of a gene, or variant nucleotide sequences at a particular locus

pyrimidines

cytosine or thymine

purine

adenine or guanine

codons

amino acids coded by triplets of nucleotides

mutation

• any alteration in nucleotide sequence of a genome

• ultimate source of genetic variation and the raw material on which natural selection acts

• result of errors in DNA replication or repair of damage by chemical mutagens or UV radiation

• must occur in germline (progenitors of gametes) to be transmitted to offspring a permanent change in the DNA sequence of an organism.

types of mutations

1. point mutation

2. insertion/deletion

3. chromosome inversions

4. gene duplication

point mutations

• Alteration of a single base in a DNA sequence 

• Transition → changing between purines (A to G or G to A) or pyrimidines (C to T or T to C)

• Transversion → changing between purines to pyrimidines or pyrimidines to purines (A to C or T; G to C or T; C to A or G; T to A or G)

transition

changing between purines (A to G or G to A) or pyrimidines (C to T or T to C)

• more frequent than transversions (~2x)

transversions

changing between purines to pyrimidines or pyrimidines to purines (A to C or T; G to C or T; C to A or G; T to A or G)

what are consequences of point mutations?

1. missense mutation — nonsynonymous replacement

2. nonsense mutation

3. silent (synonymous) mutation

missense (nonsynonymous replacement) mutation

results in an amino acid change (almost all changes happen at first and second codon positions)

synonymous (silent) mutation

does not result in an amino acid change — still get the same amino acid sequence

nonsense mutation

new codon is a stop codon; there is premature termination of translation

sickle cell is an example of _______

point mutation

insertion/deletion mutations (indels)

• “daughter” DNA has a different number of base pairs in a particular region than the “parental” DNA

• caused by errors in DNA replication, often in repetitive sequences

• In order to maintain alignment and conserve the things that are being conserved → you need to add gaps or insert things to keep it aligned

what are consequences of insertion/deletion mutations?

• can result in a frameshift mutation, insertion/deletion of amino acids in the protein, and/or premature stop codons (nonsense mutations)

chromosome inversions

• a region of DNA that has been flipped so that the genes are in reverse order

• after breakage, the segment can detach, flip, and reanneal

what can induce chromosomal breaks?

oxygen radicals, gamma-irradiation, chemicals

gene duplication

• generation of an extra copy of a locus

• most duplicated genes are generated via unequal crossing over

what are the fates of duplicated genes?

• mutations can be accumulated, which can lead to gain or loss of function of the gene