A mutation, strictly, is a heritable change in hereditary material. That material can be RNA or DNA depending on the organism (though in most organisms it is DNA), and generally mutations are considered to be more or less random changes in the nucleotide sequence of this hereditary material. Often these changes are a consequence of either nucleotide polymerization errors (i.e., replication errors) or are due to chemical modifications of nucleotide bases, or both. In this section I provide an overview of mutation, employing in part a broader perspective of mutations as changes in hereditary material that also can arise as a consequence of molecular recombination—especially recombination that follows movement of already evolved genetic material between nucleic-acid molecules. The origin and evolutionary biology of recombination as follows horizontal gene transfer will, however, be more strictly addressed in a separate chapter ("Gene Exchange"). A mutation, broadly speaking, thus can be described as a change in the nucleotide sequence of hereditary material regardless of the mechanism of that change, though generally speaking when considering mutation it is random and/or novel changes that are being considered.

Because the nucleotide sequences within organisms are more likely than not to contain evolved, i.e., natural selection-tested information, changes that occur in those sequences can modify an organism's phenotype and therefore its functioning. Since changes in nucleotide sequences, such as by mutation, typically are random (i.e., stochastic), their tendency is to reduce the information content of these sequences, that is, to reduce the amount of sequence that has previously been subject to natural selection. As a consequence, these changes are likely to reduce organism fitness, which is a measure of an organism's ability to functionally interact with its environment and then reproduce, or at best will have little or no impact on fitness. Occasionally, however, mutations can have the effect of increasing an organism's fitness, that is, mutations on relatively rare occasions will be adaptive rather than neutral or detrimental. The more information that is lost in the course of mutation, however, then the less likely that the change will be adaptive, except to the extent that possession of the original information, such as the production of a specific gene product, is costly to an organism.

Table: Types of Mutations and Related Terms

Antagonistic pleiotropy

Improvement in the utility of one aspect of phenotype in one context that results also in a decline in utility in a different context.
Antagonistic pleiotropies are differences in phenotype, especially in terms of the fitness impact of a single allele as a function of circumstances, often where benefits are provided under one or more circumstances and negative impacts (detriments) are seen under other circumstances; this is often seen in symbiotic organisms where improvement in fitness in one host, through mutation, results in decreases in fitness in another host.
Beneficial mutation

Change in the base sequence of a genome that has the effect of increasing the fitness of the so-affected organism.
When impacting phenotype, beneficial mutations have the effect of increasing the carrying organism's Darwinian fitness.

Specific aspect of phenotype, particularly one that varies phenotypically between individuals.
A character is a general characteristic of an organism, such as generation time in bacteria (eye color is a typical macroorganismal example).
Coincidental mutation

Changes at the same amino acid in independently evolving alleles.
A coincidental mutation may or may not be an indication of positive selection (see text). A coincidental mutation that becomes fixed within two or more independently evolving lineages likely is a product of positive selection. Note the temporal distinction between these two ideas where mutation refers to the initial generation of an allele whereas fixation refers to what probably are large numbers of generations into the future where that original mutation not only must have survived but also must have prospered in order to achieved fixation.
Compensatory mutation

Mutation that reduces the negative consequences of another mutation.
If the compensatory mutation is found in a different gene from the mutation it is compensating for then this represents a form of epistasis.
Conditional mutation

Trait that varies as a consequence of a change in nucleotide sequence especially from wild type but which varies only in certain environments.
Conditional mutations are as the name implies dependent in their phenotype or fitness impact on the 'conditions' in which the carrier of the mutation is found. Under some conditions the phenotype displayed is more similar to that of wild type, perhaps effectively identical, whereas under other conditions the phenotype is somewhat different, e.g., even in some cases lethal. Note the similarity between these ideas and those of antagonistic pleiotropies, that is, with an antagonistic pleiotropy there are differences in phenotype/fitness that vary as a function of environment/environmental conditions.
Convergent evolution

Appearance of similar but not identical adaptations that are a response to similar selective pressures.
Note that at a molecular level, convergent evolution is seen not so much in terms of adaptations, which are manifestations of phenotype, but instead in terms of nucleotide sequence, which is a manifestation of genotype. That is, when nucleotide sequences 'converge' towards greater similarity, this can be described as a form of convergent evolution. In either case, this convergence of form is considered to be a product of positive selection.
Deleterious mutation

Change in the base sequence of a genome that has the effect of decreasing the fitness of the so-affected organism.
To the extent that mutations are random changes in products of positive selection then it is to be expected that a substantial fraction of those changes will be detrimental. This is just as random changes in precisely manufactured artifacts (human-made devices) are expected to function less well when randomly modified.

Physical loss of nucleotides without replacement from genetic material.
A deletion is the removal/loss of a string of contiguous nucleotides. Note that when that removal occurs in nucleotide strings that are not divisible by three, within what otherwise are open reading frames of genes, then the resulting impact on gene functioning generally will be greater due to resulting frameshift mutations.
Divergent evolution

Descent with modification resulting in increasing dissimilarity between two or more species.
Divergent evolution is associated with an accumulation of genotypic and phenotypic differences between lineages due to mutation, drift, selection, or migration. Such evolution is the typical, default expectation for the separate evolution of distinct populations. In terms of nucleotide sequence, divergent evolution is seen as increasing difference between the sequences associated with independently evolving lineages as time goes on. That is, different mutations arise and then are fixed in different lineages, and these mutations also tend to have different phenotypic impacts.

Strength of natural selection relative to genetic drift as measured particularly in terms of fixed mutations in populations.
>dN/dS is the ratio of nonsynonymous to synonymous substitutions often as observed in evolved lineages where higher ratios are seen as an indication of the impact of positive selection whereas lower ratios are seen as an indication of genetic drift.

In terms of phenotype, the impact of one genetic locus on another genetic locus.
Epistasis is seen when more than one genetic locus contributes to the formation of a genetic character. Thus, a change in one of those genes can have an impact on the phenotypic expression associated with another one of this collection of genes. Note that compensatory mutations when the mutation in one gene is compensating for the phenotypic impact of a mutation in a different gene is an example of epistasis.
Frameshift mutation

Loss or gains of nucleotides other than in multiples of three, resulting in wholesale change in what downstream codons are read from mRNAs by ribosomes.
Insertions or deletions into gene reading frames other than in multiples of three nucleotides results in changes in the sense of all downstream codons. Frameshift mutations thus can give rise to huge changes in the amino acid sequence of gene's product and also can modify the overall length of a resulting polypeptide by either hiding or uncovering stop codons as found previously in different reading frames.
Insertion mutation

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Increase in number of nucleotides found in genetic material due either to mutation or recombination.
An insertion mutation, or simply insertion, is the addition of one or more nucleotides between two existing nucleotides.
Knockout mutation

Change in nucleotide sequence that eliminates the functioning of a gene and/or results in loss of a specific trait or even loss of one or more characters.
Knockout mutations result in gene knockouts, that is, a loss of normal gene functioning. Note that this knocking out is a phenotypic description, and explicitly it is a measurable loss of a phenotype. That measurable loss in phenotype, however, can be seen initially or even solely at the molecular level, such as the loss of a protein band from a gel, as a traditional means by which genetics has progressed is by "knocking out" gene functioning and then seeing what happens. What has changed, however, is the sophistication of the technologies we use to knockout genes as well as to detect to what degree genes functioning has been knocked out especially as measured at molecular levels.
Lethal mutation

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Change in nucleotide sequence that, particularly if fully expressed, can result in the loss of viability of its carrier.
If impacting phenotype, i.e., if conditional then under expressing conditions, then a lethal mutation kills the carrying organism. See also lethal allele.
Missense mutation

Conversion of one sense codon to another via modification of the nucleotide sequence of a gene.
A missense mutation is a nucleotide substitution that modifies the senses of a codon, specifically so that a different amino acid is encoded by a given position in a gene and at the corresponding position in the encoded polypeptide. A missense mutation is a nonsynonymous substitution, though the latter can describe more than just a mutation but instead the fixation of a mutation within a population as well.
Neutral mutation

Change in the base sequence of a genome that has little effect on fitness of the so-affected organism as compared with the parental sequence.
A neutral mutation in especially an evolutionary sense does not impact the Darwinian fitness of its carriers. It does not necessarily do this without impacting phenotype of its carriers, however, and any phenotypic change is not necessarily as observed or even necessarily neutral in terms of its fitness impact across all possible environments. That is, a neutral mutation can be conditional, having a neutral impact in one environment and a detrimental or even beneficial impact in others.
Nonsense mutation

Change in genome sequence, particularly a single base substitution, that results in formation of a stop codon.
Nonsense mutations result in the truncation of gene reading frames, with the consequence shorter polypeptide products than is the case prior to the nonsense mutation. The impact of nonsense mutations thus is expected to be greater the closer to a gene's start codon that the mutation occurs since as a consequence the more of the reading frame that is truncated/lost.
Nonsynonymous substitution

Mutational change in a codon that results in a change in the specified amino acid.
A nonsynonymous substitution is a missense mutation and particularly one that has become fixed within a population.
Null mutation

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Change in nucleotide sequence that results in loss of function of an allele.
A null mutation is often thought not necessarily always equivalent to missense or frameshift mutation. Compare with knockout mutation.
Parallel evolution

Changes in phenotype or genotype that are similar or even identical within closely related but nonetheless independently evolving lineages.
Parallel evolution refers to similar or identical changes in similar or identical but nonetheless independently evolving lineages. Such changes can be seen in individual genes and can be taken as evidence for the occurrence of positive selection. Traditionally parallel evolution has referred to evolved phenotypic similarities in otherwise similar lineages. In a molecular sense, however, it is the continuing similarity of nucleotide sequences despite ongoing evolution. In both cases it is not just the retention of similarities in otherwise unchanging organisms but instead change in both lineages that is similar or even identical change, i.e., fixation of same but nonetheless independently occurring mutations at the same locations.
Phenotypic plasticity

Variance in traits as a function of environments, typically as associated with wild-type genotypes.
Phenotypic plasticity is best defined in terms of non-genetic development variation in animals and plants, such as shorter trees in colder or dryer locations, but has come to be used more generally to describe simply changes in phenotype associated with a given genotype when going from environment to environment. As such, there are substantial parallels between the concept of phenotypic plasticity and that of conditional mutations with the common theme that of phenotypic differences observed in otherwise genotypically identical organisms when those organisms are located in and/or develop under distinctly different environmental conditions.

One locus impacting a diversity of characters.
A pleiotropy describes one gene having more than one impact on phenotype, i.e., an impact on more than one character. This occurs because some genes impact with a multiple of other genes or other biochemical or physiological pathways and thus a change in those core genes impacts multiple phenotypic expressions. At an extreme are core genes whose loss of function disrupts numerous pathways that are crucial for organism viability and/or fitness.
Point mutation

Change in a single nucleotide of genetic material.
Point mutations are the products of modification of individual nucleotides. These can result in missense mutation, nonsense mutations, mutations in single nucleotides not found within reading frames (SNPs or single-nucleotide polymorphisms), or mutations that change codons but not their sense (synonymous substitutions).

Phenotype restoration through genotype change but without true genotype restoration.
A pseudoreversion thus is a mutation that restores the phenotype lost with a previous mutation, but does so without actually correcting the original mutation. In a sense a pseudoreversion is a compensatory mutation in which phenotypic compensation either is or approaches 100%.

Mutational restoration of genotype following previous mutational change in genotype.
A reversion thus is a mutation that corrects a previous mutation, such as towards restoring wild type. This correction is genotypically 100%, that is, the original mutation essentially is "erased". Alternatively if the correction is seen at the phenotypic level then we can describe it as a pseudoreversion and/or as a compensatory mutation. A reversion, technically however, is not a compensatory mutations since no compensation is occurring but instead a complete reversal of the original mutation.
Silent mutation

Change in base sequence that does not result in change in what amino acids are encoded by genes.
A silent mutation is also a mutation that does not impact phenotype. Note, though, that there is a subtle difference between these two connotations since a lack of change in amino acid sequence can still result in phenotypic change if the new codon is less preferred relative to the original codon and therefore less rapidly translated (or vice versa). Thus, a silent mutations, depending upon intended meaning, may or may not be referred to an absence of phenotypic change.
Synonymous substitution

Mutational change in a codon that does not result in a change in the specified amino acid.
A synonymous substitution does not modify the sense of a codon, i.e., what amino acid is encoded. More than a mutation, however, the concept of synonymous substitution can refer to the fixation of such a mutation within a population. Note that such fixation often, though not quite only (see discussion, e.g., silent mutation), is a consequence of the action of genetic drift rather than that of natural selection.

Phenotypic variation on a character.
A trait is a specific though often genetically variable variation on a character, such as 20 min versus 30 min generation times under otherwise constant environmental conditions (in that example generation time would be the character and its specific length the trait). More familiarly, in terms of the eye color character, blue eyes would be a trait.

Point mutation that does not change the general type of nucleotide.
Change of purine to purine or pyrimidine to pyrimidine (types of nitrogenous bases). This in terms of its immediate impact of the spatial structure of the carrying double helix is a more conservative change, contrasting transversions.

Point mutation that changes the general type of nucleotide.
Change of purine to pyrimidine or pyrimidine to purine. This in terms of its immediate impact of the spatial structure of the carrying double helix is a less conservative change, contrasting transition.
Wild type

Form of an allele or genotype that is predominantly associated with organisms upon isolation from nature.
The concept of wild type is seen particularly in microbiology where an isolate as we first encounter it is considered to represent wild type and any subsequent evolution therefore representing modification from wild type. In the case of domestication of animals and plants, however, the original population that subsequently was domesticated could be viewed as representing wild type for those organisms.

Central Dogma

To understand mutation, it is helpful to appreciate what is known as the central dogma of molecular genetics. This is a description of the flow of information within cells, starting from the genome (or genotype) and flowing through to proteins (or phenotype). The processes involved include replication (which, in DNA-based organisms can be viewed as DNA-to-DNA information flow), transcription (which is the templated production of RNA, typically DNA-to-RNA information flow), and translation (which is the production of peptides and polypeptides, i.e., RNA-to-amino acid/polypeptide information flow). In addition, reverse transcription represents a flow of information from RNA to DNA. Replication, transcription, and translation, along with reverse transcription, thus are the central processes of molecular genetics. Mutations either occur or are propagated in the course of replication but in many cases impact organism functioning over the course of transcription and then translation as well.

Mutations, i.e., permanent changes in the nucleotide sequence of an organism's genome, can occur and/or are propagated during the replication step for DNA-based organisms. Alternatively, mutations can be introduced into DNA-based organisms via mechanisms involving reverse transcription. Only for RNA-based organisms, such as a number virus types, is transcription a mutagenic process, since for these organisms the permanent storage molecule of genotype is RNA. In no instance does translation contribute directly to mutation. On other hand, translational errors could give rise to lower-fidelity polymerases which themselves could be mutagenic. In addition, consequences of mutation often are not visible phenotypically until the translation step. The latter point may be better appreciated under the heading of "Types of Mutations", below. Overall, it is important to recognize that the routes by which mutations can occur in combination with the products of mutation events can be diverse, and statement that is true even before one considers that potential consequences of mutation events on organism functioning.

Table: Various Molecular Genetics Terms.


Molecular complex consisting of polynucleic acid in association with what often are numerous proteins where the nucleic acid constitutes an organism's hereditary material.
Chromosomes are the main repository or repositories of genotype located within a cell or as encapsidated within a virus.

Sequence of three nucleotides found in association with mRNA that specifies an amino acid or stop signal during translation.
Codons are sequences of three nucleotides that, in the course of translation, are converted from nucleic-acid-encoded information to specific amino acids (sense) or stop signals (nonsense). It is codons that are being modified within the context of missense mutations, nonsense mutations, synonymous substitutions, and nonsynonymous substitutions.
DNA damage

Non-heritable and also not useful change in the structure of a nucleic acid that otherwise serves to block its replication.
DNA damage is not a mutation and not an evolutionary force but instead a lesion associated with DNA, one that blocks DNA replication until repaired. This is equivalent to ink poured onto the page of a book (rather than a change in what words or letters a page contains, which would be analogous instead to a mutation). Damage can occur to RNA also, i.e., as can occur with RNA viruses.

String of nucleic acid bases that together encode the transcription of a single piece of RNA.
A gene is a nucleotide sequence that encodes the production of an RNA product. Note, though, that historically the definition of a gene has changed as an understanding of just what a gene must represent has improved. It is only with a fairly sophisticated understanding of both the central dogma of molecular genetics along with how actual organisms function that this current understanding of just what a gene represents has come into being. Nonetheless, a fairly substantial number of genes template RNA that then does on to be translated into a polypeptide product.

The bulk of hereditary material associated with individual cells or viruses.
A genome is the sum of hereditary material carried by a cell or virus and consists of nucleic acid.

An organism's hereditary information.
Genotype is the sequence of nucleotides associated with genes and other unidimensional structures encoded by DNA or, in certain viruses, RNA. It is genotype that is transmitted as hereditary material.
Hereditary material

Substance that is passed on from generation to generation that provides all of the information necessary for organism functioning.
Hereditary material consists of molecules that are transmitted from parent to offspring as a repository of genotype.

Assembly of viruses into their infectious form.
Maturation is the production of virion particles within cells and involves an association of virion proteins along with other materials with the products of virion-genome replication. Maturation is also known simply as 'assembly'.

Shorthand description (abbreviation) of nucleic acid polymer that is read by ribosomes towards synthesis (translation) of polypeptides.
mRNAs are products of gene transcription that interact with ribosomes to produce polypeptides. 'mRNA' is short for 'messenger RNA'.

Small(ish) pieces of DNA that persist within lineages of dividing cells.
Plasmids are smaller repositories of genotype which often are dispensable except under certain conditions. Plasmids generally are a form of mobile genetic element. The sexual process of conjugation is motivated by and involves the transfer of plasmids between prokaryotic organisms.
Reading frame

The codons making up a single gene.
A reading frame is the sequence of codon-encoding nucleotides that are associated with a gene. It is the reading frame that is transcribed as a substantial portion of an mRNA product. Reading frames always begin with a start codon and end with a stop codon, which are features of mRNAs that are recognized by ribosome complexes in the course of translation.

Self-duplication of genotype-carrying molecules, or of the cells or organisms carrying this hereditary material.
Replication is the duplication of nucleic acid, especially DNA. Less strictly, replication is the duplication of genotype.
Reverse transcription

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Duplication of an RNA sequence into a complementary DNA sequence.
Reverse transcription is seen most prominently in retroviruses and retrotransposons. The enzymes reverse transcriptase is responsible for catalyzing reverse transcription.
Reverse transcriptase

Enzyme that catalyzes synthesis of polydeoxyribonucleic acid (DNA) from a polyribonucleic acid (RNA) template.
Reverse transcriptase is the enzyme that is responsible for duplication of an RNA sequence into a complementary DNA sequence during the process of reverse transcription.
RNA polymerase

Enzyme responsible for transcribing genes.
RNA polymerase is the enzyme that polymerizes RNA, typically from a DNA or in some instances RNA template.
Template strand

That half of a double helix that is read by polymerase enzymes during transcription or DNA replication.
The template strand is that nucleotide strand of a double helix that is copied in the course of transcription or replication. Also known simply as template.

Templated polymerization of RNA.
Transcription is the duplication of nucleic acid sequence into a complementary RNA-based form, going either from DNA to RNA (as seen in DNA-based organisms) or from RNA to RNA (as seen in RNA-based viruses).

Conversion of specific RNA sequences into specific amino acid sequences to produce polypeptides.
Translation is the conversion of nucleic-acid-based sequence into amino-acid-based sequence, as carried out by ribosomes and as mediated from mRNA.

Mutation is not Damage

In order to appreciate what a mutation is, it is important to appreciate what a mutation is not. On the one hand, it is not exactly the product of recombination, though as noted that is a distinction that I'm not emphasizing, and especially so since such things as deletion mutations or mismatch repair, both of which can result from molecular recombination processes, either are or give rise to what legitimately may be called mutations. On the other hand, there are types of nucleic acid modifications that are most assuredly not mutations. These modifications can be differentiated into two types: Ones that are replicable (and which often are intentional, e.g., the methylations involved in epigenetic inheritance) and ones which are not replicable, at least prior to repair (and which typically are not intentional from the perspective of the organisms for which replication is blocked). The latter, not replicable and not intentional modifications to nucleic acids, can be described as nucleic acid damage.

Damages are lesions to nucleic acid, that is, unintentional modifications. Since these modifications can block replication of the damaged nucleic acid and/or lead to mutation, there are a number of mechanisms that organisms employ to repair lesions and/or that act to neutralize lesion-generating chemicals or physical processes. These mechanisms range from recombination processes to chemical reversals of lesions to destroying chemicals that have the potential to give rise to lesions to behavioral or morphological adaptations such as those that protect organisms from the ultraviolet radiation associated with sunshine. In general we can distinguish these factors that give rise to lesions into endogenous versus exogenous or environmental factors, which in both cases we can describe as nucleic acid damaging agents. The cost of failing to repair or otherwise minimizing damage is either death resulting from failure to replicate genomes or death that is perhaps only forestalled via mechanisms that deal with damage through reductions in replication fidelity, i.e., error-prone repair.

Though nucleic acid damage is a legitimate concern to organisms, it represents only one means by which organisms can sustain damage and therefore only one environmental aspect that that organisms must have various means of repairing to maintain their previous, pre-damage Darwinian fitness. That is, for example, membrane or protein damage is also a type of damage, as too is a cut or broken leg for us. What makes nucleic acid damage "special" however is a combination of the potential for damages to be converted to mutations, on the one hand, and the propensity for researchers to confuse nucleic acid damage with mutation, whereas the two phenomena are distinct: Nucleic acid damage cannot be replicated such as by DNA polymerases without first in some manner that damage being repaired whereas mutations can be replicated even if not repaired. Mutations thus are changes in nucleic acid sequence that nevertheless retains the essential nucleic acid character of serving as a template for polymerization whereas nucleic acid damage, unless repaired, represents a loss of that potential to serve as a template for nucleic acid polymerization.