In a strict sense, mutations are changes in genes not caused by genetic recombination. A change in the base sequence of DNA, for example, represents a mutational change. Spontaneous mutations are mutations that occur at a given frequency without the need for an inducing agent of change (mutagenic agent). The term mutation is also used in a less technical sense to describe changes in the human genome (i.e., evolution) that result from a broad spectrum of processes that act to increase or decrease genetic variation within a population.
By definition, a gene is a hereditary unit that carries information used to construct proteins via the processes of transcription and translation. The human gene pool is the set of all genes carried within the human population. Genetic changes, including mutations, can be beneficial, neutral or deleterious. In general, mutations, along with recombination and gene flow, act to increase genetic variation (i.e., the number of types of genes or alleles) within the human species.
The term mutation was originally used by Dutch botanist Hugo De Vries (1848–1935) to describe rapid changes in phenotype from one generation to the next. Subsequently, scientists used the term mutation to describe long-term, multi-generational, and heritable physical changes to genes.
Mutations generally occur via chromosomal mutations, point mutations, frame shifts, and breakdowns in DNA repair mechanisms. Chromosomal mutations include translocations, inversions, deletions and chromosome non-disjunction. Essentially there are five types of genetic rearrangements: deletions, duplications, inversions, translocations, and transposition.
Mutational deletions physically remove portions of genes (e.g., a portion of the DNA comprising the gene). Deletional mutations range from the single base point mutations to mutations that can span many functional genes. Chemical and radioactive agents account for the majority of induced point mutations. Scientists currently argue that most cancers and other degenerative diseases result from acquired genetic mutations due to environmental exposure, and not as an outcome of inherited traits. Chemicals capable of inducing genetic mutation (i.e., chemical mutagenesis or genotoxic compounds) are present a wide variety of natural and man-made products.
Point mutations may be nonsense mutations leading to the early termination of protein synthesis, missense mutations (a mutation that results an a substitution of one amino acid for another in a protein), or silent mutations that cause no detectable change. Accordingly, the effects of point mutational changes range from 100% lethality (all individuals die, usually early in fetal development) to no observable (phenotypic) change.
Duplications result in multiple copies of genes, and can occur as a result of unequal crossover or chromosome breaks. In addition, because some alteration of DNA is inevitable in the replication process, any mutation that hinders DNA repair mechanism will also increase the chance that a mutation will go uncorrected. Duplications also manifest a range of deleterious effects.
Inversions, which are changes in the orientation of gene bearing chromosomal regions, may cause deleterious effects if the inversion breaks through a gene critical for a particular protein or enzyme.
Translocations occur when one a portion of one chromosome becomes linked to a non-homologous chromosome (a chromosome outside its normal pairing) or
Recombination involves the reassortment of genes through new chromosome combinations. Recombination occurs via an exchange of DNA between homologous chromosomes (crossing over) during meiosis. Recombination also includes linkage disequilibrium. With linkage disequilibrium, variations of the same gene (alleles) occur in different combinations in the gametes (sexual reproductive cells) than should occur according to the rules of probability.
Gene flow occurs when individuals change their local genetic group by moving from one place to another. These migrations allow the introduction of new variations of the same gene (alleles) when they mate and produce offspring with members of their new group. In effect, gene flow acts to increase the gene pool in the new group. Because genes are usually carried by many members of a large population that has undergone random mating for several generations, random migrations of individuals away from the population or group usually do not significantly decrease the gene pool of the group left behind.
In contrast to mechanisms that operate to increase genetic variation, there are fewer mechanisms that operate to decrease genetic variation. Mechanisms that decrease genetic variation include genetic drift and natural selection.
Genetic drift results form the changes in the numbers of different forms of a gene (allelic frequency) that result from sexual reproduction. Genetic drift can occur as a result of random mating (random genetic drift) or be profoundly affected by geographical barriers, catastrophic events (e.g., natural disasters or wars that significantly affect the reproductive availability of selected members of a population) and other political-social factors.
Natural selection is based upon the differences in the viability and reproductive success of different genotypes with a population (differential reproductive success). Natural selection can only act on those differences in genotype that appear as visible (phenotypic) differences that affect the ability to attract a mate and produce viable offspring that are, in turn, able to live, mate and continue the species. The term evolutionary fitness describes the success of an entity in reproducing (i.e., contributing alleles to the next generation).
There are three basic types of natural selection. With directional selection, an extreme phenotype is favored (high or low body fat). Stabilizing selection occurs when an intermediate phenotype is fittest (e.g., body fat content is neither too high nor low) and for this reason it is often referred to a normalizing selection. Disruptive selection occurs when two extreme phenotypes are fitter than an intermediate phenotype. In studying changes in the human genome, the operation of natural evolutionary mechanisms is complicated by geographic, ethnic, religious, and social groups and customs. Accordingly, the effects of various evolution mechanisms on human populations are not as easy to predict. Increasingly sophisticated statistical studies are carried out by population geneticists to characterize changes in the human genome.
K. Lee Lerner