BIOL 243 Theme 2D Pt. 1

Changes in DNA sequences and spontaneous mutations

Mutations - how they occur in the genome

mutations: changes to nucleic acid sequence (DNA and RNA)

* can be inherited (germline) or not inherited (somatic)
* altered gene sequence can change the aa sequence of the polypeptide resulting in variation of phenotype
* effect on phenotype can be neutral, harmful, beneficial
* primary force in evolution where natural selection favours beneficial mutations

Spontaneous vs induced mutations

Spontaneous: naturally-occurring mainly caused by replication errors and spontaneous lesions

* spontaneous lesions include depurination and deamination of bases

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Induced: natural/environment or artificial agent or mutation that causes mutations at a rate higher than spontaneous mutagens

* mutagens: induce mutations by replacing a base/alter base so it mispairs w another base/damages a base where it can no longer pair w any base
* base analogs: mimic bases and incorporates into DNA (can cause mispairing during DNA replication)
* chemicals that alter base structure to cause mispairing
* damage to bases - UV light-thymine dimers, etc

Germline vs somatic mutations

Germline: mutation originally occurred in gametes and therefore becomes heritable

* ex. sex influenced trait

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Somatic: can occur in all other cell types except games, not heritable

* mutation occurs in a progenitor cell and all other daughter cells will express the mutation
* somatic mutations are expressed as sectors - size depends on time of mutation
* ex. cancer tumours

How mutations can change the amino acid sequence of a polypeptide

Small scale - changes to one or few base pairs

* base substitution: single nucleotide change as a result of point mutations
* insertion: 1 or more base pairs added in sequence during DNA replication → frameshift mutation
* deletion: 1/more base pairs skipped during DNA replication → frameshift mutation
* transitions: purine-to-purine or pyrimidine-to-pyrimidine changes
* transversions: purine-to-pyrimidine or vice versa

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Point mutations → aa sequence

* missense mutation (non-synonymous): codon change causes change in aa
* nonsense mutation (premature stop): sense codon change to stop codon → truncated polypeptide
* silent mutation (synonymous): codon change doesn’t change aa bc of degeneracy of genetic code
* frameshift mutation: insertion/deletion → alters reading frame

Consequences of mutations on fitness and phenotypes

Mutations can affect an organism by changing its physical characteristics (or phenotype) or it can impact the way DNA codes the genetic information (genotype). When mutations occur they can cause termination (death) of an organism or they can be partially lethal.

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may result in:

* loss of function alleles: mutations that reduce/eliminate gene function/expression
* gain of function alleles: mutations that enhance gene function/expression

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How mutants in genetic model systems can help infer function of genes

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Many model organisms can breed in large numbers. Mutants allow scientists to study certain observable characteristics or diseases.

Alleles

one of different forms of a gene (sequence variation) which can cause different phenotypes

Types of alleles and their effect on gene function

* wild-type allele: normal form of the gene found in nature/standard lab strain of a model organism
* loss of function alleles: mutations that reduce/eliminate gene function/expression
* gain of function alleles: mutations that enhance gene function/expression