8: Mutation and Recombination

Ultimate source of variation

Mutation.

Mutation → variation for natural selection → evolution

Inter-specific variation

Different traits / characteristics observed between different species.

Intra-specific variation

Different traits / characteristics observed within the same species.

Recombination

Shuffles genetic material around, which creates new variation.

Major sources of mutations

Errors in DNA replication.

Errors in chromosome segregation (during anaphase).

Transposition (transposable elements), DNA damage, aberrant recombination.

Types of mutations

Point mutations

Insertions / deletions (indels)

Large events

Rearrangements

Point mutations

One substitution of a nucleotide (A → G; G → C; etc.)

Types of silent mutations

Silent — synonymous mutations that do not change the amino acid sequence.

Missense — nonsynonymous mutations that change one amino acid in a protein.

Nonsense — stops the codon, disrupts the sequence, and production is terminated; often highly deleterious and very visible.

Insertion / deletion (indels) mutations

Additional nucleotides are inserted or deleted from the original DNA, rather than changing a nucleotide.

This includes frameshift mutations.

Frameshift mutation

Indels that alter the reading frame used during translation of the mRNA for all regions downstream.

Number of base pairs inserted or deleted is not divisible by 3.

Large event mutations

Usually highly deleterious for animals (kills or sterilizes them), but not always for plants.

Somy mutations — changes in the number of chromosomes in an organism.

Whole-genome duplications — process where an organism’s entire genetic material is copied, resulting in multiple sets of chromosomes (polyploidy).

Rearrangement mutations

Inversion — the order of a section of the genome has been reversed (flipped).

Translocation — sections of two chromosomes are exchanged.

Errors

These are not mutations, but they lead to mutations.

Sources of errors

Spontaneous errors in DNA replication (slip-strand mispairing).

Physical damage to DNA (UV light / intercalating agents).

Segregation errors (sexual reproduction; anaphase during meiosis).

Non-homologous recombination (aberrant recombination).

Mobile elements (transposons).

Direct vs indirect sources of errors

Direct — changing the base sequence.

Indirect — increasing frequency of replication and segregation.

Slip-Strand Mispairing

During DNA replication, the strand being copied gets dissociated (separated) and can lead to contraction (deletion event) or expansion (insertion event).

Aberrant recombination

Unusual forms of recombination that can lead to chromosomal rearrangements, often resulting in deleterious mutations.

Mutation rate in humans

Homo sapiens has 1 × 10^-10 per site per replication.

It is only 1 mutation per 10 billion sites.

Protection from mutations

Pigments — melanin protects animals by absorbing UV irradiation.

Cell wall — protects plants / fungi / bacteria from chemical agents.

Prevention of mutations

DNA Ligase (T4) repairs the backbone of damaged DNA.

SOS response in single-celled bacteria allow them to survive DNA changes.

Homologous recombination — two pieces of DNA that are identical (or nearly) in sequence are aligned and a section of DNA is exchanged.

Correction of mutations

Proofreading — identify instances of incorrect base pairs and fix them.

Petri dishes 

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Variation of mutation rates

Different types of mutations occur at different rates.

Both the rate and pattern of mutation differ greatly in different species.

Same types of mutations can occur at different rates in different regions of the genome or in different individuals.

Basic concepts of mutation

Mutation (and recombination) are independent of their consequences for fitness.

Selection does not trigger mutations; mutations already existed and become apparent underneath certain conditions (selection).

Different mutations (silent / missense / nonsense) occur at different rates.

Mutation rates can vary across the genome (high mutation rate with low expression rate).

Generation of variation by mixing (recombination and random segregation).

Negative correlation

If the mutation rate is high, then the expression rate is usually low, and vice versa.

Large organisms (with large genomes) typically have low mutation rates.