Mutations are changes in the DNA sequence that occur spontaneously during cell division or through environmental exposure. These changes are the raw material of evolutionary change, and scientists categorize them based on their effect on an organism. While some mutations are harmful or occasionally helpful, many have no discernible effect on an organism’s survival or ability to reproduce. This specific category of changes, which is far more common than the other types, is known as a neutral mutation.
Defining Neutral Mutations
A neutral mutation is defined as an alteration in the DNA sequence that does not affect the reproductive success, or fitness, of the organism carrying it. The change is neither advantageous nor disadvantageous under the organism’s current environmental conditions. Since they do not confer a survival benefit or penalty, neutral mutations can persist in a population without being actively favored or removed by natural selection.
The concept of neutrality depends entirely on the impact on the whole organism, not just the molecular change itself. Only changes that fail to produce any measurable difference in viability or fecundity are truly considered neutral. For example, a mutation might alter a protein structure, but if that alteration does not affect how well the organism functions, it remains classified as neutral. Most molecular variation observed within and between species is thought to result from these neutral changes.
The Molecular Basis of Neutrality
A mutation can be neutral for several molecular reasons related to the structure of the genetic code and genome organization. One common mechanism is the synonymous mutation, often called a silent mutation. The genetic code is redundant, meaning most amino acids are coded for by multiple three-letter sequences, or codons.
If a single base pair changes in the DNA, and the resulting messenger RNA codon still specifies the same amino acid, the protein sequence remains unchanged. Since the protein is identical to the original version, its function is preserved, and the mutation is neutral. This phenomenon is common in the third position of a codon, sometimes referred to as the “wobble hypothesis.”
Another source of neutral change involves mutations in the vast portions of the genome that do not code for proteins. Only about two percent of the human genome consists of protein-coding genes; the rest is non-coding DNA, including introns, regulatory elements, and spacer sequences. A mutation in these regions is neutral if it does not interfere with the nearby gene’s expression, such as by disrupting a regulatory protein binding site.
Finally, changes that do alter the amino acid sequence can still be neutral, known as a neutral amino acid substitution. This happens when the new amino acid is chemically very similar to the original one, such as replacing one nonpolar amino acid with another. In these cases, the protein’s three-dimensional shape and active site remain functional, causing no loss of activity or fitness.
Neutrality and Natural Selection
Neutral mutations occupy a specific position within the spectrum of genetic changes, alongside deleterious and beneficial mutations. Deleterious mutations decrease an organism’s fitness and are typically removed quickly by natural selection. Beneficial mutations, which increase fitness, are rare and are actively favored and spread by selection.
Neutral mutations are unique because they are effectively invisible to the pressures of natural selection. Since they have no impact on survival or reproduction, the environment cannot favor or disfavor the individuals that carry them. Their fate within a population is determined not by selective pressure but by chance events.
The primary force acting on neutral mutations is genetic drift, the random fluctuation of allele frequencies from one generation to the next. By chance, some individuals will leave more offspring than others, and the neutral alleles they carry will increase in frequency, regardless of their lack of selective value. Genetic drift can cause a neutral mutation to become “fixed” (spread throughout the entire population) or lost entirely. The neutral theory of molecular evolution posits that most molecular variation within a species is governed by the balance between mutation and random genetic drift.
Examples of Neutral Mutations and Their Impact
Neutral mutations have significant applications in both genetics and evolutionary biology. One clear example is the high rate of mutation observed in pseudogenes, which are non-functional DNA segments that resemble active genes. Because pseudogenes no longer produce a necessary protein, they are no longer under the purifying pressure of selection.
Consequently, mutations accumulate in pseudogenes at a high, constant rate because nearly all changes are neutral, providing a reference point for studying mutation rates in functional DNA. The accumulation of neutral changes also forms the basis of the molecular clock. This concept uses the constant rate of neutral mutation fixation to estimate the time when two species last shared a common ancestor.
Neutral mutations are also invaluable tools in population genetics studies, where they are used as molecular markers. Highly variable non-coding sequences, such as microsatellites or certain single nucleotide polymorphisms (SNPs), are often considered neutral. Researchers use the random changes in the frequencies of these markers to trace population movements, assess genetic diversity, and reconstruct the ancestry of species, free from the influence of natural selection.