Fact-checked by Grok 2 weeks ago

Mutant

A mutant is an organism, cell, or genetic element that differs from the wild type due to a mutation, defined as a permanent change in its DNA sequence that alters its genetic material.^[1]^[2] These changes can result in new characteristics or phenotypes, distinguishing the mutant from its parental or standard form.^[2] Mutations leading to mutants occur through various mechanisms, including errors during DNA replication in cell division, exposure to environmental mutagens such as radiation or chemicals, or viral infections.^[3] Common types of mutations include point mutations (single nucleotide changes), insertions or deletions that cause frameshifts, and larger structural variations like duplications or inversions, each potentially affecting protein function or gene regulation.^[4]^[5] In humans and other organisms, such genetic alterations can be germline (inherited) or somatic (acquired during life), influencing traits from benign variations to disease states like cancer.^[6] Mutants play a pivotal role in biological research and evolutionary biology, serving as models to elucidate gene functions, pathways, and adaptations.^[7] Techniques like site-directed mutagenesis intentionally create mutants to study protein structures or metabolic processes, while natural mutants have driven evolutionary changes by providing genetic diversity upon which natural selection acts.^[7]^[8] For instance, beneficial mutations in populations can lead to adaptations, such as antibiotic resistance in bacteria, highlighting mutants' significance in understanding heredity and disease.^[8] In popular culture, the concept of mutants extends beyond biology to depict fictional entities with enhanced or altered abilities due to genetic changes, often symbolizing themes of difference, discrimination, and human evolution.^[9] In Marvel Comics, mutants are distinguished from mutates, with mutants born possessing the X-gene granting innate powers, while mutates acquire abilities through external factors like radiation or chemicals.^[10] Iconic examples include the X-Men in Marvel Comics and films, where mutants represent marginalized groups through analogies to real-world social issues like racism and LGBTQ+ rights.^[9] DC Comics formerly used "mutant" but shifted to "metahuman," a term first used by author George R.R. Martin in 1986 in the Superworld role-playing game to refer to superpowered humans, and subsequently in his Wild Cards novel series, before appearing in comic book fiction in Marvel's New Mutants Annual #3 (1987), to broadly classify superpowered individuals.^[11] Similarly, the Teenage Mutant Ninja Turtles franchise, which originated as a parody of Marvel Comics series such as Daredevil and the New Mutants (debuting in 1982–1983, predating the 1986 coining of "metahuman" by George R.R. Martin), portrays mutants as anthropomorphic animals transformed by a mutagenic substance, blending science fiction with adventure narratives.^[12]^[13] These portrayals have popularized the term, influencing public perceptions of genetics and mutation in media from comics to blockbuster films.^[13]

Definition and Fundamentals

Definition

In biology, a mutant refers to an organism, gene, or chromosome that differs from the wild type due to one or more heritable changes in its genetic material, primarily the DNA sequence, which produces distinct characteristics.^[2]^[1] These changes represent permanent alterations in the hereditary information, often leading to observable phenotypic differences from the standard form found in a population.^[3] Unlike polymorphisms, which are common genetic variations occurring at frequencies greater than 1% within a population and typically neutral in effect, mutants arise from rarer genotypic modifications that can impact function, viability, or appearance.^[14]^[15] Such mutations occur either spontaneously through errors in DNA replication, repair, or recombination, or are induced by external mutagens like ionizing radiation or certain chemicals, resulting in the creation of new alleles that may be inherited across generations.^[16]^[17]^[18] The concept of a mutant emerged in early 20th-century genetics, particularly through Thomas Hunt Morgan's pioneering experiments with fruit flies (Drosophila melanogaster), where he documented variants such as the white-eyed mutant to elucidate patterns of inheritance.^[19]^[20]

Etymology

The term "mutant" derives from the Latin verb mutare, meaning "to change," with the noun form entering English in the late 19th to early 20th century specifically in biological contexts to denote an organism exhibiting a sudden, heritable alteration.^[21] The related term "mutation," referring more broadly to change or alteration, first appeared in English in the late 14th century from Latin mutatio, but its genetic application emerged later.^[22] In scientific usage, "mutant" gained prominence through the work of Dutch botanist Hugo de Vries, who in his 1901 publication Die Mutationstheorie described mutants as plants arising from abrupt, discontinuous heritable changes observed in evening primroses (Oenothera species), contrasting them with gradual variations.^[23] De Vries's theory emphasized mutations as saltatory events—large, non-blending shifts that could produce new species directly—differing from Darwinian "variation," which he viewed as minor, continuous fluctuations insufficient for speciation without natural selection.^[24]

Mechanisms of Mutation

Genetic Mutations

Genetic mutations are permanent alterations in the DNA sequence that can lead to the production of genetic mutants, arising from either spontaneous or induced processes at the molecular level. These changes occur during fundamental cellular activities such as DNA replication, repair, and recombination, or through exposure to external agents, fundamentally altering the genetic information passed to daughter cells or offspring.^[25] Spontaneous mutations primarily result from intrinsic errors in DNA replication, where DNA polymerase occasionally incorporates incorrect nucleotides, leading to base substitutions, or from slippage during replication of repetitive sequences, causing insertions or deletions (indels). These errors can also arise during DNA repair processes, such as mismatches not corrected by proofreading mechanisms, or from aberrant recombination events during mitosis or meiosis that misalign homologous chromosomes and generate sequence alterations. In humans, the spontaneous mutation rate is estimated at approximately $1.2 \times 10^{-8} per base pair per generation, reflecting the balance between error-prone replication and corrective repair systems.^[25]^[26]^[27]^[28] Induced mutations are triggered by environmental mutagens that damage DNA, increasing the frequency of sequence changes beyond baseline spontaneous rates. Physical mutagens like ultraviolet (UV) radiation cause the formation of thymine dimers by linking adjacent thymine bases, distorting the DNA helix and leading to errors during replication if unrepaired. Chemical mutagens, such as the alkylating agent ethyl methanesulfonate (EMS), modify DNA bases—often by adding ethyl groups to guanine—resulting in base mispairing and substitutions during subsequent replication cycles. Biological mutagens, including transposons (mobile genetic elements), induce mutations by inserting into or excising from the genome, disrupting genes or altering regulatory sequences during transposition events in mitotic or meiotic cells.^[26]^[29]^[30] The mutation rate \mu, a key metric for quantifying these events, is calculated as the number of observed mutations divided by the product of the number of loci examined, the number of individuals studied, and the number of generations observed, providing an estimate of mutations per locus per generation in experimental or natural populations. This formula underpins mutation accumulation studies, revealing how spontaneous and induced processes contribute to genetic variation while distinguishing sequence-based changes from non-sequence epigenetic alterations.^[31]^[25]

Epigenetic Alterations

Epigenetic alterations refer to heritable changes in gene expression that do not involve modifications to the underlying DNA sequence, distinguishing them from genetic mutations by affecting how genes are read and regulated rather than altering the genetic code itself.^[32] These changes play a key role in modulating phenotypic traits in response to environmental cues, and while they can be stable across cell divisions, they are often reversible, unlike the permanent sequence alterations seen in classical genetic mutations.^[33] In the context of mutants, epigenetic alterations are sometimes termed "epimutations," but they do not produce new alleles or variants in the genome, positioning them outside the traditional definition of mutagenesis in genetics.^[34] The primary mechanisms of epigenetic alterations include DNA methylation, histone modifications, and non-coding RNA regulation. DNA methylation typically involves the addition of methyl groups to cytosine bases, particularly at CpG islands in promoter regions, which can repress gene transcription by inhibiting transcription factor binding or recruiting repressive proteins.^[35] Histone modifications, such as acetylation and deacetylation of lysine residues on histone tails, alter chromatin structure; for instance, acetylation loosens chromatin to promote gene activation, while deacetylation compacts it to silence genes.^[36] Non-coding RNAs, including microRNAs and long non-coding RNAs, further regulate expression by targeting messenger RNAs for degradation or by guiding chromatin-modifying complexes to specific loci.^[36] Epigenetic alterations can exhibit heritability, being transmitted through mitosis and, in some cases, meiosis across generations, though they are generally more labile than genetic changes. In plants, paramutation exemplifies this, where an allele induces a heritable epigenetic state in a homologous allele, leading to stable, meiotically inherited reductions in gene expression without DNA sequence changes; this has been observed in maize, where the paramutagenic b1 allele silences the bw locus via RNA-directed DNA methylation.^[37] Unlike genetic mutations, these epimutations can revert under certain conditions, such as environmental shifts, allowing for phenotypic plasticity.^[38] Notable examples include epimutations in cancer, where hypermethylation of promoter regions silences tumor suppressor genes like p16 and MLH1, promoting tumorigenesis; this was first systematically described in colorectal and other cancers, highlighting how such changes contribute to neoplastic progression without genetic alterations.^[39] Environmental influences also drive heritable epimutations, as seen in the Dutch Hunger Winter of 1944–1945, where prenatal exposure to famine led to persistent reductions in DNA methylation at growth-related genes like IGF2 in exposed individuals six decades later, correlating with increased risks of metabolic disorders.^[40] These cases underscore that while epigenetic alterations enable adaptive responses, they are not classified as "true" mutants in classical genetics, as they modify expression levels rather than creating heritable sequence variants.^[32]

Types of Mutations

Point Mutations

Point mutations, also known as single nucleotide substitutions, are the smallest scale alterations in DNA, involving the replacement of a single nucleotide base with another. These changes can occur spontaneously or due to environmental factors and represent the most fundamental type of genetic mutation.^[41] Point mutations are classified into two primary categories based on the chemical nature of the nucleotide substitution: transitions and transversions. Transitions involve the replacement of a purine base (adenine [A] or guanine [G]) with another purine, or a pyrimidine base (cytosine [C] or thymine [T]) with another pyrimidine, such as A↔G or C↔T. Transversions, in contrast, involve the substitution of a purine for a pyrimidine or vice versa, for example, A↔C or G↔T. Transitions occur more frequently than transversions due to the biochemical similarities between the bases involved, with transitions accounting for approximately two-thirds of all point mutations in the human genome.^[41]^[42] The phenotypic impact of point mutations depends on their effect at the protein level, categorized as silent, missense, or nonsense. Silent mutations do not alter the amino acid sequence of the encoded protein because they occur in the third position of a codon, where the genetic code is degenerate, resulting in no change to protein function. Missense mutations substitute one amino acid for another, potentially altering protein structure and function depending on the chemical properties of the replacement; these can be conservative (similar amino acids) or non-conservative (dissimilar), leading to mild or severe effects. Nonsense mutations introduce a premature stop codon (UAA, UAG, or UGA in mRNA), truncating the protein and often causing loss-of-function, which can be detrimental if the truncated product lacks essential domains.^[43]^[43]^[43] A classic example of a missense point mutation is the one responsible for sickle cell anemia, where a single nucleotide substitution in the HBB gene (encoding the beta-globin chain of hemoglobin) changes the codon from GAG to GTG, resulting in the replacement of glutamic acid (Glu) with valine (Val) at position 6 (p.Glu6Val). This alteration causes hemoglobin molecules to polymerize under low-oxygen conditions, leading to red blood cell sickling, vaso-occlusion, and hemolytic anemia. In cystic fibrosis, the nonsense mutation G542X in the CFTR gene exemplifies loss-of-function; this C-to-T transition at nucleotide 1624 creates a premature stop codon (TAG), producing a truncated CFTR protein that fails to function as a chloride channel, impairing mucociliary clearance and causing respiratory and digestive complications.^[44]^[45] Point mutations are detected primarily through DNA sequencing techniques, such as Sanger sequencing for targeted analysis or next-generation sequencing for genome-wide identification, which allow precise identification of the substituted base and its location. These mutations' effects on protein function are assessed via functional assays, such as protein expression studies or biochemical activity measurements, revealing disruptions like reduced stability or altered interactions. As single nucleotide polymorphisms (SNPs), point mutations constitute the most common form of genetic variation in humans, accounting for approximately 90% of all known DNA variants across the genome.^[46]^[47]

Insertion and Deletion Mutations

Insertion and deletion mutations, collectively known as indels, involve the addition or removal of one or more nucleotide bases in the DNA sequence. These can range from single nucleotides to larger segments and are distinct from substitutions, often leading to significant disruptions in gene reading frames. Small indels (typically 1–50 base pairs) are particularly common and can cause frameshift mutations if the number of bases added or removed is not a multiple of three, shifting the codon reading frame and altering all downstream amino acids in the protein. In-frame indels, where the change is a multiple of three, may result in the addition or loss of amino acids without shifting the frame, potentially affecting protein function to a lesser degree.^[48]^[5] Indels arise from errors in DNA replication, repair, or recombination, such as slippage during polymerase activity in repetitive sequences. A well-known example is the ΔF508 mutation in cystic fibrosis, a three-base-pair deletion in the CFTR gene that removes a phenylalanine residue (p.Phe508del), leading to misfolded protein and impaired chloride transport. Another is the four-base-pair insertion in the HBB gene causing β-thalassemia, which results in a frameshift and premature termination, reducing hemoglobin production. Indels contribute to genetic diversity and disease, with detection via sequencing methods that identify length variations, such as PCR-based fragment analysis or next-generation sequencing.^[49]^[4]

Structural Mutations

Structural mutations, also referred to as structural variants, encompass large-scale genomic rearrangements that alter chromosome structure and involve segments ranging from thousands to millions of base pairs, often disrupting multiple genes and regulatory elements.^[50] These alterations contrast with smaller-scale changes like point mutations by their potential to affect gene dosage, positioning, or expression across broad regions, leading to phenotypic mutants in organisms.^[51] The primary types of structural mutations include deletions, duplications, inversions, and translocations. Deletions involve the loss of a chromosomal segment, resulting in haploinsufficiency for affected genes; a notable example is cri-du-chat syndrome, caused by a deletion on the short arm of chromosome 5 (5p-), which leads to partial monosomy and characteristic clinical features.^[52] Duplications create extra copies of genetic material, often causing gene dosage imbalances; for instance, Charcot-Marie-Tooth disease type 1A arises from a 1.4 Mb duplication on chromosome 17p12 encompassing the PMP22 gene, resulting in demyelination of peripheral nerves.^[53] Inversions reverse the orientation of a chromosomal segment, potentially disrupting gene function or regulation by altering cis-regulatory elements.^[51] Translocations exchange segments between non-homologous chromosomes, which can juxtapose oncogenes with active promoters; the Philadelphia chromosome, formed by t(9;22)(q34;q11), is a reciprocal translocation driving chronic myeloid leukemia through BCR-ABL1 fusion.^[54] These mutations typically arise through error-prone DNA repair or recombination processes. Unequal crossing-over during meiosis, a form of misalignment between homologous chromosomes, generates deletions and duplications by unequal exchange of genetic material.^[55] Non-allelic homologous recombination (NAHR) occurs between low-copy repeats, facilitating recurrent rearrangements like those in CMT1A.^[51] Breakage-bridge-fusion cycles, involving unstable dicentric chromosomes, can propagate complex inversions and translocations, particularly in cancer contexts.^[56] Structural mutations are detectable via cytogenetic and molecular techniques, including karyotyping for visible chromosomal abnormalities and array comparative genomic hybridization (array CGH) for higher-resolution mapping of copy number variations.^[57] In disease contexts, such as Burkitt lymphoma, MYC translocation to immunoglobulin loci (e.g., t(8;14)) deregulates oncogene expression, predisposing cells to proliferation and contributing to cancer development.^[58] These variants also influence fertility by disrupting meiotic pairing or gamete viability, and they elevate cancer risk through genomic instability.^[51]

Biological Significance

Role in Evolution

Mutations that confer a selective advantage play a pivotal role in adaptive evolution by enhancing organismal fitness and spreading through populations under natural selection. For example, in bacterial populations exposed to antibiotics, beneficial mutations in genes encoding efflux pumps, such as those increasing norA expression in Staphylococcus aureus, reduce intracellular drug concentrations, thereby improving survival and enabling the rapid evolution of resistance.^[59] These adaptive mutants demonstrate how rare advantageous variants can become prevalent when environmental pressures favor their transmission, driving population-level changes over generations. The neutral theory of molecular evolution, first articulated by Motoo Kimura in 1968, asserts that the vast majority of molecular changes fixed in evolving lineages are selectively neutral, neither improving nor harming fitness, and thus governed primarily by random genetic drift rather than deterministic selection.^[60] Under this framework, neutral mutations accumulate at a rate approximately equal to the mutation rate itself, contributing to substantial genetic variation within species without immediate phenotypic consequences, which serves as a substrate for future evolutionary contingencies.^[61] In small or fragmented populations, genetic drift exerts a stronger influence, increasing the probability of fixation for neutral or even mildly deleterious mutations that would be purged by selection in larger groups. The founder effect exemplifies this process, where a limited number of individuals colonize a new habitat—such as island species deriving from mainland ancestors—resulting in non-representative allele frequencies and elevated risks of deleterious allele fixation due to stochastic sampling.^[62] This drift-mediated fixation can erode genetic diversity and compromise long-term adaptability, particularly in isolated populations where effective population sizes remain low.^[63] Fundamentally, mutations provide the essential raw material for evolutionary processes by introducing heritable variation that natural selection, drift, and other forces can act upon to shape biodiversity.^[64] The equilibrium between mutation rates and selection maintains this variability, as recurrent mutations replenish alleles removed by purifying selection, ensuring a dynamic pool of genetic diversity that balances adaptive potential against the burden of deleterious variants.^[65]

Effects on Organisms

Mutations exert a profound influence on the physiology and phenotype of organisms, with the majority being deleterious, thereby reducing individual fitness by impairing essential functions or causing disease. In humans, for instance, mutations in the phenylalanine hydroxylase (PAH) gene lead to phenylketonuria (PKU), an inborn error of metabolism where elevated phenylalanine levels result in severe intellectual disability, seizures, and behavioral disturbances if untreated. This autosomal recessive disorder exemplifies how loss-of-function mutations disrupt metabolic pathways, accumulating toxic intermediates that damage the central nervous system and other tissues. Similarly, across species, most genetic mutations are harmful, often decreasing survival or reproductive success by altering protein structure or expression in ways that compromise cellular processes.^[66]^[67] While deleterious effects predominate, some mutations are neutral, exerting no significant impact on fitness, or rarely beneficial, conferring advantages under specific conditions. A notable beneficial example is the CCR5-Δ32 deletion, with an allele frequency of approximately 10% in individuals of European descent (corresponding to about 1% homozygotes resistant to HIV-1 infection due to impaired viral entry into cells via the CCR5 receptor and 10-15% heterozygotes with slower disease progression),. Neutral mutations, by contrast, typically occur in non-coding regions or result in synonymous changes that do not alter protein function, allowing genetic variation to accumulate without phenotypic consequence. These neutral or advantageous cases highlight the spectrum of mutational outcomes, though beneficial mutations remain exceedingly rare compared to their harmful counterparts.^[68]^[67] The phenotypic manifestations of mutations vary by organism, reflecting differences in genome complexity and environmental interactions. In bacteria such as Escherichia coli and Salmonella, auxotrophic mutants arise from disruptions in biosynthetic pathways, rendering them unable to synthesize essential nutrients like amino acids (e.g., L-lysine) or vitamins (e.g., biotin), thus requiring exogenous supplements for growth and survival. In humans, radiation-induced mutations during fetal development can produce teratogenic effects, including congenital malformations like microcephaly, intrauterine growth restriction, and intellectual impairment, particularly when exposure occurs during organogenesis (weeks 2-8 post-conception) at doses exceeding 0.1-0.2 Gy. These organism-specific impacts underscore how mutations can disrupt development or metabolism in ways tailored to the biological context, often leading to dependency or severe developmental anomalies.^[69]^[70] Organisms exhibit genetic robustness that can mitigate mutational effects through mechanisms like redundancy, where paralogous genes—arising from duplication events—provide functional backups. For example, loss of one paralog in the mammalian circadian clock, such as Cryptochrome 1, triggers upregulation of its duplicate, maintaining rhythmic gene expression and masking the mutation's impact on physiology. This compensation via paralogous redundancy preserves fitness by buffering against deleterious changes, allowing organisms to tolerate genetic perturbations without immediate phenotypic loss. Such robustness is widespread, enabling cryptic variation to persist until environmental shifts reveal its consequences.^[71]

Applications and Examples

In Genetic Research

Mutants have been instrumental in genetic research as experimental tools for elucidating gene functions and regulatory pathways in model organisms. By inducing or identifying mutations that alter specific traits, researchers can infer the roles of genes through phenotypic analysis, establishing causal links between genotype and biological processes. This approach underpins both forward and reverse genetics methodologies, enabling systematic dissection of complex genetic networks.^[72] A foundational example comes from early 20th-century studies using Drosophila melanogaster. In 1910, Thomas Hunt Morgan discovered a white-eyed male fly, a spontaneous mutant that led to the identification of sex-linked inheritance. Through controlled breeding experiments, Morgan demonstrated that the white-eye trait was carried on the X chromosome, providing evidence for chromosomal theory of heredity and marking the first use of mutants to map genes to chromosomes. This work established Drosophila as a premier model for genetic analysis due to its short generation time and observable traits. Building on such phenotypic screens, George Beadle and Edward Tatum advanced the field in 1941 by using irradiation-induced auxotrophic mutants in the fungus Neurospora crassa. These mutants, unable to synthesize essential nutrients like vitamins or amino acids, revealed that specific genes control individual biochemical reactions, leading to the one-gene-one-enzyme hypothesis. By correlating mutant phenotypes with enzyme deficiencies, their experiments demonstrated that genes encode functional proteins, a cornerstone of modern molecular biology. This forward genetics approach—inducing random mutations and screening for selectable phenotypes—remains a staple for identifying gene functions, as exemplified by the Ames test developed in 1973. In this bacterial assay, histidine auxotroph mutants of Salmonella typhimurium are exposed to potential mutagens, with reversion to prototrophy indicating mutagenic activity, thus screening for environmental hazards through mutant reversion rates. In Caenorhabditis elegans, RNA interference (RNAi) has enabled efficient knockout mutants since the late 1990s, allowing researchers to silence specific genes and study loss-of-function phenotypes. Pioneered by Andrew Fire and Craig Mello in 1998, double-stranded RNA triggers sequence-specific mRNA degradation, producing transient or heritable knockdowns that mimic null mutants. This technique has facilitated large-scale genetic screens in C. elegans, uncovering pathways in development and behavior, and has been extended to other models for pathway analysis. Complementing forward genetics, reverse genetics employs targeted mutagenesis to test hypotheses about known genes. The advent of CRISPR-Cas9 in 2012 has revolutionized this by enabling precise, inducible mutations in model organisms. For instance, CRISPR guides the Cas9 nuclease to cleave specific DNA sequences, inducing insertions or deletions that disrupt gene function, as demonstrated in early applications to Drosophila, C. elegans, and mice. This method allows rapid generation of knockouts, bypassing the need for homologous recombination and accelerating functional validation. Such techniques find broad applications in gene mapping and developmental studies. In Drosophila and yeast, mutant screens have mapped thousands of loci by recombination analysis, linking phenotypes to chromosomal positions. In mammalian models like mice, targeted Hox gene mutants have illuminated body patterning; for example, disruption of Hoxa11 results in limb skeletal transformations, revealing its role in proximodistal patterning during embryogenesis. These insights from Hox cluster knockouts underscore how mutants dissect regulatory cascades, informing evolutionary biology and, briefly, therapeutic strategies for congenital disorders.

In Medicine and Biotechnology

In medicine, the study of genetic mutations has enabled the development of diagnostic tools that identify disease-predisposing variants, allowing for early intervention and personalized risk assessment.^[73] For instance, genetic testing for mutations in the BRCA1 and BRCA2 genes, identified in the mid-1990s, assesses elevated risks of breast and ovarian cancers, with carriers facing lifetime breast cancer risks up to 72% for BRCA1 and 69% for BRCA2.^[74] These tests, commercially available since the late 1990s following advancements in DNA sequencing, guide clinical decisions such as enhanced screening or prophylactic surgeries.^[75] Therapeutic applications leverage mutation knowledge to correct or mitigate genetic defects. CRISPR-Cas9 gene editing, adapted from bacterial defense mechanisms, has been used to repair mutations causing sickle cell disease by editing patient-derived hematopoietic stem cells ex vivo, with the first treatments administered in clinical trials starting in 2019 and leading to FDA approval of Casgevy in 2023 for sustained hemoglobin production.^[76]^[77] Pharmacogenomics further tailors drug therapies to individual mutation profiles, optimizing efficacy and reducing adverse reactions; for example, testing for CYP2C19 variants guides antiplatelet dosing in cardiovascular patients to prevent clotting variability.^[78]^[79] In biotechnology, engineered mutations in microorganisms facilitate the large-scale production of therapeutic proteins. Recombinant human insulin, produced by introducing the human insulin gene into Escherichia coli via recombinant DNA technology developed in 1978, marked the first FDA-approved biotech drug in 1982, replacing animal-derived insulin and treating millions with diabetes while minimizing immunogenicity risks.^[80] This approach has since expanded to other biologics, using mutant strains for efficient expression and purification. Ethical concerns arise particularly with germline editing, which could transmit alterations to future generations. The 2018 case of Chinese scientist He Jiankui, who used CRISPR-Cas9 to edit CCR5 genes in human embryos to confer HIV resistance, resulting in the birth of twin girls, sparked global condemnation for bypassing safety protocols, lacking informed consent, and risking off-target effects. He was sentenced to three years in prison in December 2019 and released in April 2022. As of 2025, he has resumed research on gene editing for genetic diseases, reigniting debates on the ethics of heritable edits, while calls for international moratoriums persist.^[81]^[82]^[83]^[84]^[85]

References

[1]
20.1: Mutations and Mutants - Biology LibreTexts
Apr 27, 2019 · A mutation is a change in the genetic material - DNA sequence - of an organism. By extension, a mutant is the organism in which a mutation has occurred.
[2]
Mutant Definition and Examples - Biology Online Dictionary
Jul 21, 2021 · (1) An organism, gene, or chromosome that is different from the wild type by one or more (new) characteristics as caused by mutation(s).
[3]
Mutation - National Human Genome Research Institute
Definition. A mutation is a change in the DNA sequence of an organism. Mutations can result from errors in DNA replication during cell division, exposure to ...
[4]
What Is a Genetic Mutation? Definition & Types - Cleveland Clinic
A genetic mutation is a change to a gene's DNA sequence to produce something different. It creates a permanent change to that gene's DNA sequence.
[5]
Types of mutations - Understanding Evolution
There are many different ways that DNA can be changed, resulting in different types of mutation. Here is a quick summary of a few of these.
[6]
Definition of mutation - NCI Dictionary of Cancer Terms
Any change in the DNA sequence of a cell. Mutations may be caused by mistakes during cell division, or they may be caused by exposure to DNA-damaging agents ...
[7]
Genetics, Mutagenesis - StatPearls - NCBI Bookshelf
Sep 19, 2022 · Mutagenesis is a technique used in molecular biology to create mutant genes, proteins, and organisms. Two primary mutagenesis techniques are ...
[8]
The population genetics of mutations: good, bad and indifferent - PMC
Mutations are caused by physical changes to the hereditary material and, because DNA is a long sequence of base pairs organized into physically unlinked ...2. Mutations · (b). Linkage Theories · (c). Epistatic Interactions...
[9]
Genetics in the X-Men film franchise: mutants as allegories of ...
Jan 3, 2024 · Mutants in the films evoke a plurality of analogies, such as mutant-as-Black and mutant-as-queer. These intersecting metaphors build upon a core ...
[10]
Unraveling DNA's role in pop culture—from superheroes to crime ...
Apr 25, 2024 · Now we have some very popular universes of mutants, including the Spider-Verse, Teenage Mutant Ninja Turtles, and X-Men. 2. DNA spans old and ...<|control11|><|separator|>
[11]
Genetic Polymorphism - an overview | ScienceDirect Topics
In contrast to a mutation, polymorphisms do not necessarily cause diseases ... Genetic polymorphism is defined as the occurrence within a population of two or ...
[12]
Defining “mutation” and “polymorphism” in the era of personal ... - NIH
Jul 15, 2015 · Mutations usually arise from unrepaired DNA damage, replication errors, or mobile genetic elements. There are several major classes of DNA ...
[13]
Mutation, Repair and Recombination - Genomes - NCBI Bookshelf
(A) A mutation is a small-scale change in the nucleotide sequence of a DNA molecule. A point mutation is shown but there are several other types of mutation, as ...
[14]
The causes of mutations - Understanding Evolution
Mutations occur from inaccurate DNA copying, spontaneous DNA breakdown, and exposure to chemicals or radiation. Sloppy DNA repair can also cause mutations.Missing: alleles | Show results with:alleles
[15]
What is Mutation? - Learn Genetics Utah
Mutation creates slightly different versions of the same genes, called alleles. These small differences in DNA sequence make every individual unique.
[16]
Thomas Hunt Morgan: The Fruit Fly Scientist - Nature
Morgan wanted to understand heredity and mutation, which is genetic change. After teaching for 13 years at Bryn Mawr College, he moved on to Columbia ...
[17]
Thomas Hunt Morgan – Article - NobelPrize.org
Apr 20, 1998 · Morgan's first attempts to find tractable mutations to study were quite disappointing. Fortunately, he persevered and found the white-eyed fly.
[18]
Mutant - Etymology, Origin & Meaning
From Latin mutare meaning "to change," mutant (noun, 1900) means an individual altered by genetic mutation; adjective use dates from 1903; sci-fi sense from ...
[19]
https://www.nature.com/scitable/topicpage/thomas-hunt-morgan-the-fruit-fly-scientist-6579789/
[20]
Die mutationstheorie - Biodiversity Heritage Library
Feb 12, 2009 · Die mutationstheorie. Versuche und beobachtungen über die entstehung von arten im pflanzenreich. By Vries, Hugo de, 1848-1935.
[21]
Roles of Mutation and Selection in Speciation: From Hugo de Vries ...
Sep 6, 2011 · ... word mutation to indicate only the genetic changes of single genes. However, at the time of de Vries, the genetic cause of mutations was not ...
[22]
https://onlinelibrary.wiley.com/doi/10.1002/humu.10021
[23]
Mutation accumulation under UV radiation in Escherichia coli - Nature
Nov 6, 2017 · Irradiation with UV radiation induces thymine dimer lesions in DNA sequences. The unrepaired lesions increase the rate of replication ...
[24]
Similarities and differences in patterns of germline mutation between ...
Sep 6, 2019 · Whole genome sequencing (WGS) studies have estimated the human germline mutation rate per basepair per generation (~1.2 × 10−8) to be higher ...
[25]
DNA Damage & Repair: Mechanisms for Maintaining DNA Integrity
The rate at which DNA polymerase adds incorrect nucleotides during DNA replication is a major factor in determining the spontaneous mutation rate in an organism ...
[26]
Mutagenic Effectiveness of Ethyl Methanesulphonate and Methyl ...
The monofunctional alkylating agent ethyl methanesulphonate (EMS) has been shown to be capable of producing mutations in more than one-half of the spikes of ...
[27]
https://www.nature.com/articles/s41467-019-12023-w
[28]
Spontaneous mutation rate estimates for the principal malaria ...
Jan 7, 2022 · The mutation rate per base per generation estimated in humans was 1.2 × 10−8 in two separate studies and was associated with a higher mutation ...
[29]
Genetics, Epigenetic Mechanism - StatPearls - NCBI Bookshelf - NIH
Epigenetics is the study of heritable and stable changes in gene expression that occur through alterations in the chromosome rather than in the DNA sequence.
[30]
Epigenetics and gene expression | Heredity - Nature
May 12, 2010 · Epigenetic processes, including DNA methylation, histone modification and various RNA-mediated processes, are thought to influence gene expression.
[31]
How epigenetic mutations can affect genetic evolution: Model and ...
Apr 12, 2013 · Heritable epigenetic mutations have higher mutation and reversion rates than genetic mutations, but can still be acted on by natural ...
[32]
Epigenetic regulation in metabolic diseases: mechanisms ... - Nature
Mar 2, 2023 · We will discuss four epigenetic regulatory mechanisms: DNA methylation, histone modification, chromatin remodelling, and ncRNA. All of them can ...
[33]
Targeting epigenetic regulators for cancer therapy - Nature
Dec 17, 2019 · Through DNA methylation, histone modification, chromatin remodeling, and noncoding RNA regulation, epigenetics play an important role in ...
[34]
Paramutation: the tip of an epigenetic iceberg? - PMC
Paramutation describes the transfer of an acquired epigenetic state to an unlinked homologous locus, resulting in a meiotically heritable alteration in gene ...
[35]
Epigenetic memory in plants | The EMBO Journal
Epigenetics refers to heritable changes in patterns of gene expression that occur without alterations in DNA sequence.Mitotically Heritable... · Imprinting--Memory Of... · Meiotically Heritable...
[36]
Hypermethylation of tumor suppressor genes in cancer - PubMed
Hypermethylation of tumor suppressor genes and other genes functionally important in the neoplastic process is a recently recognized process.Missing: epimutations seminal paper
[37]
Persistent epigenetic differences associated with prenatal exposure ...
Nov 4, 2008 · Here we show that individuals who were prenatally exposed to famine during the Dutch Hunger Winter in 1944–45 had, 6 decades later, less DNA ...Missing: 1959-1960 | Show results with:1959-1960
[38]
Chapter 12: DNA Damage and Repair - Chemistry
A transition mutation is a point mutation that changes a purine nucleotide to another purine (A ↔ G) or a pyrimidine nucleotide to another pyrimidine (C ↔ T).
[39]
Mutation Rates in Humans. II. Sporadic Mutation-Specific ... - NIH
These rates are as follows: transitions at CpG sites 9.7×10-8, other transitions 7.3×10-9, transversions at CpG sites 5.4×10-9, other transversions 6.9×10-9, ...<|separator|>
[40]
3.2: Consequences of mutations - Biology LibreTexts
Jan 8, 2023 · Silent mutations: do not change the encoded amino acid · Nonsense mutations: change a codon to a STOP codon · Missense mutations: change a codon ...
[41]
Sickle Cell Disease—Genetics, Pathophysiology, Clinical ...
May 7, 2019 · Sickle cell disease (SCD) is a monogenetic disorder due to a single base-pair point mutation in the β-globin gene resulting in the substitution ...
[42]
Pharmacological Responses of the G542X-CFTR to CFTR Modulators
Jun 23, 2022 · G542X-CFTR, a premature termination codon (PTC) mutation, is the most common disease-associated mutation found in the remaining 10% of patients ...Abstract · Introduction · Materials and Methods · Results
[43]
Chapter 6 A. Mutation - Biology
A single base pair replacement (point mutation) may decrease or eliminate function of a gene, resulting in lethality. Example, Sickle-cell anemia. Problem (4): ...
[44]
Non-STR DNA Markers: SNPs, Y-STRs, LCN and mtDNA | Single ...
Jul 20, 2023 · The most common form of genetic variation in the human genome (approximately 90%) is a class of genetic marker known as a single nucleotide polymorphism (SNP).Missing: proportion | Show results with:proportion
[45]
Insights into structural variations and genome rearrangements in ...
SVs can be broadly classified into five major classes—Deletions, Duplications, Insertions, Inversions and Translocations.
[46]
Mechanisms of structural chromosomal rearrangement formation - NIH
Jun 14, 2022 · Switching to an upstream position leads to duplication, to a downstream position leads to deletion, to a sequence in the opposite orientation ...
[47]
Cri Du Chat Syndrome - StatPearls - NCBI Bookshelf - NIH
Oct 25, 2022 · Cri du chat syndrome is a genetic disorder caused by a deletion of the short arm of chromosome 5. The name of the syndrome means the cry of the cat.
[48]
Charcot-Marie-Tooth Disease: Seventeen Causative Genes - PMC
Tandem duplication of the CMT1A region within chromosome 17p11.2-p12, including the PMP22 gene, is the most frequent cause of CMT type 1.16 This duplication is ...
[49]
The Philadelphia chromosome in leukemogenesis - PMC
The Philadelphia chromosome (Ph) is the truncated chromosome 22 generated by the reciprocal translocation t(9;22)(q34;q11) and was first identified in 1960 in ...
[50]
Change of Gene Structure and Function by Non-Homologous End ...
Such chromosomal rearrangements include deletions, insertions, duplications, inversions, and translocations, and they can occur by transposition, unequal ...
[51]
Chromosome structural variation in tumorigenesis: mechanisms of ...
Nov 10, 2020 · Deletions are the most common and simplest structural variant, followed by tandem duplications and unbalanced translocations [1]. Meanwhile, the ...
[52]
Array CGH as a first line diagnostic test in place of karyotyping for ...
Apr 5, 2013 · Array CGH is a robust and cost-effective alternative to traditional cytogenetic methodology; it provides a higher diagnostic detection rate than ...
[53]
Oncogenic Mechanisms in Burkitt Lymphoma - PMC - PubMed Central
The translocation of MYC in BL occurs exclusively to the nonproductively rearranged IG heavy-chain locus, sparing the allele that produces the productive IG ...
[54]
Efflux pump activity potentiates the evolution of antibiotic resistance ...
Aug 7, 2020 · norA expression could increase the fitness benefit provided by resistance mutations in the presence of ciprofloxacin by reducing the fitness ...
[55]
Evolutionary Rate at the Molecular Level - Nature
Download PDF. Article; Published: 17 February 1968. Evolutionary Rate at the Molecular Level. MOTOO KIMURA. Nature volume 217, pages 624–626 (1968)Cite this ...
[56]
The importance of the Neutral Theory in 1968 and 50 years on - NIH
The Neutral Theory of Molecular Evolution asserts that most de novo mutations are either sufficiently deleterious in their effects on fitness that they have ...
[57]
Bottlenecks and founder effects - Understanding Evolution
Genetic drift can cause big losses of genetic variation for small populations. Population bottlenecks occur when a population's size is reduced for at least ...
[58]
Evolution of drift robustness in small populations - PMC - NIH
Oct 18, 2017 · Genetic drift can reduce fitness in small populations by counteracting selection against deleterious mutations. Here, LaBar and Adami ...
[59]
Studying Mutation and Its Role in the Evolution of Bacteria - PMC - NIH
If mutation is a Poisson process and if mutations occur after and in response to viral exposure, one would expect the number of resistant mutants following ...Missing: etymology | Show results with:etymology
[60]
Applicability of the Mutation–Selection Balance Model to Population ...
Apr 19, 2019 · Protein-truncating variants (PTVs) are expected to evolve under strong purifying selection and to have a relatively high per-gene mutation rate.Missing: raw | Show results with:raw
[61]
PAH gene: MedlinePlus Genetics
Apr 25, 2023 · Hundreds of variants (also called mutations) in the PAH gene have been identified in people with phenylketonuria (PKU). This condition ...
[62]
Fitness Reversals and the Ascent of Deleterious Mutations
Mutations are the fuel of natural selection. It is widely believed that most mutations are deleterious, that is, they harm the organisms in which they occur.
[63]
HIV Resistant Mutation | Viruses101 | Learn Science at Scitable
Oct 6, 2013 · A genetic mutation found mostly in people of European descent delays the progression of AIDS and in some cases even brings about immunity.
[64]
Metabolic and genetic basis for auxotrophies in Gram-negative ... - NIH
Mar 4, 2020 · Other auxotrophic mutants with increased fitness included biotin, 4-aminobenzoyl glutamate, L-isoleucine and L-valine, L-lysine, and L-leucine ...
[65]
Radiation Effects on the Fetus - StatPearls - NCBI Bookshelf
Significant sequelae of radiation-induced damage are fetal growth restriction and congenital malformations, particularly of the central nervous system seen as ...Introduction · Function · Issues of Concern · Clinical Significance
[66]
Robustness: mechanisms and consequences - PMC - PubMed Central
One seemingly straightforward mechanism of robustness is simple redundancy in the form of gene duplicates [38]. Compensation by a paralog need not be passive; ...
[67]
Moving forward with forward genetics - PubMed Central - NIH
In addition, unlike chemical mutagens or radiation, CRISPR allows the generation of mutant libraries with known mutation sites. On one side, the development and ...Missing: Ames test
[68]
BRCA Gene Changes: Cancer Risk and Genetic Testing Fact Sheet
Jul 19, 2024 · The risks of developing breast and ovarian cancer are markedly increased in people who inherit a harmful change in BRCA1 or BRCA2.
[69]
BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian ...
Mar 20, 2025 · BRCA1- and BRCA2-associated hereditary breast and ovarian cancer (HBOC) is characterized by an increased risk for female and male breast cancer, ovarian cancer.
[70]
Lessons learned from two decades of BRCA1 and BRCA2 genetic ...
Nearly a generation (~24 years) has elapsed since the identification of the breast cancer susceptibility genes, BRCA1 and BRCA2.
[71]
CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β ...
Dec 7, 2020 · We report the investigational use of CRISPR-Cas9–based gene editing to treat two cases of inherited diseases: one in a patient with TDT and the ...
[72]
FDA Approves First Gene Therapies to Treat Patients with Sickle ...
Dec 8, 2023 · Casgevy is the first FDA-approved therapy utilizing CRISPR/Cas9, a type of genome editing technology. Patients' hematopoietic (blood) stem cells ...
[73]
Pharmacogenomics: The Right Drug to the Right Person - PMC - NIH
Pharmacogenomics holds the promise that drugs might one day be tailor-made for individuals and adapted to each person's own genetic makeup.
[74]
Pharmacogenomics Overview - StatPearls - NCBI Bookshelf - NIH
Aug 2, 2025 · Pharmacogenetics originated from intermittent genetic studies that focused on drug responses related to specific gene mutations.
[75]
100 Years of Insulin | FDA
Jun 8, 2022 · In 1978 scientists at City of Hope and Genentech developed a method for producing biosynthetic human insulin (BHI) using recombinant DNA ...
[76]
Making sense of it all: Ethical reflections on the conditions ...
Sep 16, 2020 · In November 2018 the birth of the first genome-edited human beings was announced by Chinese scientist, He Jiankui. The ensuing ethical ...
[77]
CRISPR'd babies: human germline genome editing in the 'He ...
The world was shocked in Nov. 25, 2018 by the revelation that He Jiankui had used clustered regularly interspaced short palindromic repeats ('CRISPR') to edit ...
[78]
How do regular people in the Marvel universe distinguish between mutants and mutates?
Explanation of the distinction between mutants (born with X-gene) and mutates (acquired powers) in Marvel Comics.
[79]
Metahuman - Hey Kids Comics Wiki
Details on the origin of the term "metahuman" coined by George R.R. Martin in 1986 and its adoption in DC Comics.
[80]
Metamutants | Marvel Database
Description of metamutants in the Amalgam Universe as individuals with super-powers born with the metamutant gene.
[81]
The Teenage Mutant Ninja Turtles Started As A Marvel Parody
Article confirming TMNT's origins as a parody of Marvel's Daredevil and broader 1980s trends including elements from New Mutants.