D1.3 Mutation and gene editing

A mutation is a change in the nucleotide sequence of DNA.

Insertions and deletions may cause a frameshift, altering all downstream codons, whereas substitutions usually affect only one codon
Base substitution: one nucleotide is replaced by another
Insertion: one or more nucleotides are added to the sequence
Deletion: one or more nucleotides are removed from the sequence

A single-nucleotide polymorphism (SNP) is a variation at a single nucleotide position in the DNA sequence that is common within a population.

Base substitutions in coding regions may result in:
= Silent mutations (no change in amino acid due to degeneracy)
= Missense mutations (change in amino acid)
= Nonsense mutations (premature stop codon)

Base substitutions in non-coding regions often have no effect, but may:
= alter gene expression if regulatory sequences are affected
= affect mRNA splicing
The degeneracy of the genetic code (multiple codons coding for the same amino acid) reduces the impact of some substitutions by allowing no change in amino acid sequence.

Silent (same-sense): base substitution that does not change the amino acid
Missense: base substitution that changes one amino acid
Nonsense: base substitution that creates a stop codon, producing a truncated polypeptide

A frameshift mutation is a change in the reading frame caused by insertion or deletion of nucleotides not in multiples of three.

cause a frameshift, altering the reading frame
change all downstream amino acids (extensive missense)
introduce premature stop codons
produce a non-functional polypeptide

A mutagen is a physical or chemical agent that increases the rate of mutation.

Gene mutations can be caused by:
spontaneous errors during DNA replication or repair
mutagens, including:
= chemical agents (e.g. base analogues, alkylating agents)
= radiation (e.g. UV light, ionizing radiation)

Mutations occur randomly, meaning they are not caused by the needs of the organism = There is no natural mechanism to deliberately change a specific DNA sequence
Random mutations are the ultimate source of new alleles -> This generates genetic variation within populations
Genetic variation provides the raw material for natural selection -> Beneficial mutations may increase in frequency, while harmful ones are selected against
Random mutations in germ cells are heritable, allowing evolutionary change over generations
Mutation rate may be increased by mutagens, but the type and location remain random

Germ cells are cells that produce gametes by meiosis and are haploid = Mutations in germ cells are heritable and can be passed to offspring
Somatic cells are body cells that divide by mitosis and are diploid = Mutations in somatic cells are not inherited and only affect the individual

Germ cell
Germ cell mutations occur in cells that form gametes = These mutations are heritable and can be passed to offspring
They may be present in all cells of the offspring after fertilization
Germline mutations contribute to genetic variation and evolution

SOmatic cell
Somatic mutations occur in body cells after fertilization = They are not inherited and only affect the individual
They may lead to localized effects, such as cancer or tissue dysfunction
Somatic mutations do not contribute to evolution

Genetic variation is the differences in alleles or DNA sequences between individuals of a population.

New alleles arise by gene mutation.

Gene mutation produces new alleles by altering the DNA sequence = It is the only process that creates new genetic information
Other processes (e.g. meiosis and sexual reproduction) only rearrange existing alleles
This variation provides the basis for natural selection and evolution

Beneficial mutations increase survival and reproductive success and may be selected for
Neutral mutations have no effect on phenotype or fitness (often due to genetic code degeneracy)
Harmful mutations reduce survival or reproductive success and are often selected agains