6.7 Mutations

Mutations are random changes in DNA. Some come from mistakes in DNA replication or DNA repair that slip past proofreading. Others are caused by outside factors, such as UV light and other radiation, or reactive chemicals that damage DNA. A mutation can change the amount or type of protein a cell makes, and through that, the phenotype. Because mutations create new alleles, they're the ultimate source of genetic variation.

You won't be asked to memorize specific mutations and their effects; the examples below (sickle-cell disease and cystic fibrosis) are just for illustration.

• Point mutation (substitution): one nucleotide is replaced by another.
• Silent mutation: a substitution that doesn't change the amino acid, because the new codon codes for the same one (thanks to the redundant genetic code).
• Missense mutation: a substitution that changes one amino acid. The effect ranges from none to severe, depending on where it is in the protein. In sickle-cell disease, a single substitution swaps glutamic acid for valine in hemoglobin, which makes the proteins stick together and deform red blood cells.
• Nonsense mutation: a substitution that creates a premature stop codon, cutting the protein short, which usually makes it nonfunctional.
• Frameshift mutation: an insertion or deletion of a number of nucleotides that isn't a multiple of three. Every codon after it is read in the wrong frame, so usually the rest of the protein is wrong and a stop codon appears early.
• An insertion or deletion of exactly three nucleotides adds or removes one amino acid without shifting the frame. The most common mutation causing cystic fibrosis is like this: three bases are deleted from the CFTR gene, removing one amino acid and disrupting a channel protein that moves chloride ions.

Whether a mutation is beneficial, harmful or neutral depends on its effect on the protein and on the environment. A mutation in the pigment gene MC1R gives some rock pocket mice dark fur; on dark lava rock that's camouflage and helps them survive, but on pale sand it makes them easy prey. Many mutations are neutral, landing in noncoding DNA or causing silent changes.

Errors in mitosis or meiosis can change chromosome number. Nondisjunction (5.2) produces cells with an extra or missing chromosome, which is called aneuploidy. Trisomy (three copies of one chromosome) and monosomy (one copy) often cause developmental problems because the balance of gene products is off. Having entire extra sets of chromosomes is polyploidy (triploid, 3n; tetraploid, 4n); it's usually lethal in animals but common in plants. Changes in chromosome structure, such as a deleted, duplicated or relocated segment, can also cause genetic disorders. You don't need to know specific chromosomal disorders by name.

Bacteria reproduce asexually, but they gain new genes through horizontal gene transfer, moving DNA between cells rather than from parent to offspring:

• Transformation: a cell takes up loose DNA from its surroundings.
• Transduction: a virus that infects bacteria accidentally carries bacterial DNA from one cell to another.
• Conjugation: two cells connect and one transfers DNA, often a plasmid, directly to the other.
• Transposition: segments of DNA called transposons ('jumping genes') move within or between DNA molecules, for example from a plasmid to the chromosome.
• Viral recombination: when two related viruses infect the same host cell, they can swap genetic material and produce a new strain. New flu strains can arise this way.