Mutation is the fundamental biological process that generates the raw material for all genetic differences observed in life. It is defined as a permanent alteration in the nucleotide sequence of an organism’s DNA or RNA. Genetic variation describes the differences in DNA sequences among individuals within a population. Mutation is the event that creates a new version of a gene, while genetic variation is the resulting diversity of those versions across a species. Every instance of genetic variation originated as a mutation, providing the diversity necessary for biological change and adaptation.
Categorizing Mutations by Scale
Mutations are categorized based on the physical scope of the change to the genetic material.
Point Mutations
On the smallest scale are point mutations, which affect only a single base pair within the DNA sequence. This includes a substitution, where one base is swapped for another, or a small insertion or deletion of one or a few base pairs. These changes are frequent and often occur during DNA replication.
Chromosomal Mutations
On a much larger scale are chromosomal mutations, which involve extensive structural changes to the chromosomes themselves. These changes can affect hundreds or thousands of genes at once. Examples include duplications, where a segment is repeated, and inversions, where a segment is broken off, flipped, and reinserted. Translocations occur when a segment of one chromosome attaches to a different, non-homologous chromosome. The resulting altered sequence or structure is the first step in creating a new genetic variant.
Functional Outcomes of DNA Changes
The physical changes to the DNA sequence translate into genetic variation by altering the instruction set for building proteins. If a point mutation occurs within a protein-coding region, the result depends on how the change affects the three-base-pair codons.
A silent mutation is a change in the DNA that results in the same amino acid being encoded due to the redundancy of the genetic code. The DNA sequence varies, but the resulting protein does not, meaning the variation is hidden at the functional level.
A missense mutation occurs when the base change leads to the incorporation of a different amino acid into the protein chain. This substitution can range from having a negligible effect to dramatically altering the protein’s structure and function, which creates functional variation.
A nonsense mutation is particularly disruptive because it changes an amino acid codon into a premature stop codon. This results in a truncated, non-functional protein, effectively eliminating the gene product’s activity.
Small insertions or deletions of one or two base pairs can cause a frameshift mutation. Because the genetic code is read in triplets, adding or removing a base shifts the reading frame for every subsequent codon. This change scrambles the entire downstream amino acid sequence, almost always yielding a completely non-functional protein.
Environmental and Internal Triggers of Mutation
Mutations arise from two primary sources: spontaneous errors during normal cellular processes and exposure to external agents.
Spontaneous Errors
The most common source of new mutations is the error rate that occurs during DNA replication. Although the DNA polymerase enzyme is highly accurate, it occasionally inserts an incorrect nucleotide, creating a mismatch that can become a permanent mutation if not corrected. Spontaneous chemical changes, such as tautomeric shifts, can also alter a base’s pairing properties and lead to replication errors. These internal, chance events are responsible for the vast majority of new variations.
External Mutagens
External factors, known as mutagens, trigger changes by directly damaging the DNA structure. Environmental radiation, such as ultraviolet light, causes adjacent bases to bond incorrectly, forming structures called pyrimidine dimers. Chemical mutagens, including those found in tobacco smoke or industrial pollutants, can chemically modify bases or insert themselves into the DNA strand. A mutation becomes permanent and heritable only when cellular repair mechanisms fail to restore the original sequence.
Integrating New Mutations into Population Variation
A mutation only contributes to the overall genetic variation of a species if it is passed down to the next generation. This depends on whether the change occurs in somatic cells (body cells) or germline cells (sperm and egg cells).
Somatic mutations may affect the individual organism, but they are not inherited by offspring. Only a mutation that occurs in the germline can be transmitted to the next generation, where it introduces a new allele into the population’s gene pool.
Once introduced, the fate of this new variant is determined by population dynamics. Forces like gene flow, the movement of individuals or gametes between populations, can spread the new allele geographically. Genetic drift, the random fluctuation of allele frequencies, may cause the new variant to become more or less common purely by chance. Mutation provides the continuous input of novel genetic material, while other evolutionary mechanisms determine whether that new variation persists, spreads, or is lost from the species over time.