Phenotype

{{Short description|Composite of the organism's observable characteristics or traits}} {{For |a non-technical introduction to the topic |Introduction to genetics}} {{Other uses}} [[File:Coquina variation3.jpg|thumb|right|250px |The shells of individuals within the bivalve mollusk species ''Donax variabilis'' show diverse coloration and patterning in their phenotypes.]] [[File:Punnett square mendel flowers.svg|thumb|right |Here the relation between genotype and phenotype is illustrated, using a Punnett square, for the character of petal color in pea plants. The letters B and b represent genes for color, and the pictures show the resultant phenotypes. This shows how multiple genotypes (BB and Bb) may yield the same phenotype (purple petals).]]

In genetics, the '''phenotype''' ({{etymology|grc|''{{wikt-lang|grc|φαίνω}}'' ({{grc-transl|φαίνω}})|to appear, show||''{{wikt-lang|grc|τύπος}}'' ({{grc-transl|τύπος}})|mark, type}}) is the set of observable characteristics or traits of an organism.<ref name="Oxford Advanced Learners Dictionary at OxfordLearnersDictionaries.com">{{cite web | title= Phenotype adjective – Definition, pictures, pronunciation and usage notes | website=Oxford Advanced Learner's Dictionary at OxfordLearnersDictionaries.com | url=https://www.oxfordlearnersdictionaries.com/definition/english/phenotype?q=phenotype | access-date=2020-04-29 | quote=the set of observable characteristics of an individual.}}</ref><ref name="Understanding Evolution">{{cite web | title=Genotype versus phenotype | website=Understanding Evolution | url=https://evolution.berkeley.edu/evolibrary/article/genovspheno_01 | access-date=2020-04-29 | quote=An organism's genotype is the set of genes that it carries. An organism's phenotype is all of its observable characteristics — which are influenced ... by its genotype and by [an organism's interactions with] the environment.}}</ref> The term covers all traits of an organism other than its genome, however transitory: the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological properties whether reversible or irreversible, and all its behavior, such as a peacock's display.<ref name="West-Eberhard">West-Eberhard, Mary Jane. ''Developmental Plasticity and Evolution.'' Oxford: Oxford University Press, 2003, Oxford University Press, p.31 {{ISBN|978-0-19-512234-3}}</ref>

An organism's phenotype results from two basic factors: the expression of an organism's unique profile of genes (its genotype) and the influence of environmental factors experienced by that same organism which influence the variable expression of said genes, and thereby shape the resulting profile of defining traits. Since the developmental process is a complex interplay of gene-environment, gene-gene interactions, there is a high degree of phenotypic variation in a given population that extends beyond mere genotypic variation.<ref>{{Cite web |title=Phenotype |url=https://www.genome.gov/genetics-glossary/Phenotype |access-date=2026-01-14 |website=www.genome.gov |language=en}}</ref>

A well-documented example of polymorphism is Labrador Retriever coloring; while the coat color depends on many genes, it is clearly seen in the environment as yellow, black, and brown. Richard Dawkins in 1978<ref name=r1/> and again in his 1982 book ''The Extended Phenotype'' suggested that one can regard bird nests and other built structures such as caddisfly larva cases and beaver dams as "extended phenotypes".

Wilhelm Johannsen proposed the genotype–phenotype distinction in 1911 to make clear the difference between an organism's hereditary material and 'all the typical phenomena of the organic world', the description of which, with regard 'to forms, structures, sizes, colors and other characters of the living organisms has been the chief aim of natural history'.<ref>{{cite journal | vauthors = Churchill FB | title = William Johannsen and the genotype concept | journal = Journal of the History of Biology | volume = 7 | issue = 1 | pages = 5–30 | year = 1974 | pmid = 11610096 | doi = 10.1007/BF00179291 | s2cid = 38649212 }}</ref><ref>{{cite journal | vauthors = Johannsen W | title = The genotype conception of heredity. 1911 | journal = International Journal of Epidemiology | volume = 43 | issue = 4 | pages = 989–1000 | date = August 2014 | pmid = 24691957 | pmc = 4258772 | doi = 10.1086/279202 | jstor = 2455747 }}</ref> The distinction somewhat resembles that proposed by August Weismann (1834–1914), who distinguished between germ plasm (heredity) and somatic cells (the body). More recently in ''The Selfish Gene'' (1976), Dawkins redescribed these concepts as replicators and vehicles.

==Definition== {{Redirect|Phenome|the speech unit|Phoneme}}

{{Anchor|Definition}}Despite its seemingly straightforward definition, the concept of the phenotype has hidden subtleties. It may seem that anything dependent on the genotype is a phenotype, including molecules such as RNA and proteins. Most molecules and structures coded by the genetic material are not visible in the appearance of an organism, yet they are observable (for example by Western blotting) and are thus part of the phenotype; human blood groups are an example. It may seem that this goes beyond the original intentions of the concept with its focus on the (living) organism in itself. Either way, the term phenotype includes inherent traits or characteristics that are observable or traits that can be made visible by some technical procedure.{{cn|date=May 2024}} thumb|ABO blood groups determined through a Punnett square and displaying phenotypes and genotypes The term "phenotype" has sometimes been incorrectly used as a shorthand for the phenotypic difference between a mutant and its wild type, which would lead to the false statement that a "mutation has no phenotype".<ref name="pmid12884976">{{cite journal | vauthors = Crusio WE | title = 'My mouse has no phenotype' | journal = Genes, Brain and Behavior | volume = 1 | issue = 2 | page = 71 | date = May 2002 | pmid = 12884976 | doi = 10.1034/j.1601-183X.2002.10201.x | s2cid = 35382304 | author-link = Wim Crusio | doi-access = free }}{{cbignore|bot=medic}}</ref>

Behaviors and their consequences are also phenotypes, since behaviors are observable characteristics. '''Behavioral phenotypes''' include cognitive, personality, and behavioral patterns. Some behavioral phenotypes may characterize psychiatric disorders<ref>{{cite journal | vauthors = Cassidy SB, Morris CA | title = Behavioral phenotypes in genetic syndromes: genetic clues to human behavior | journal = Advances in Pediatrics | volume = 49 | pages = 59–86 | date = 2002-01-01 | pmid = 12214780 }}</ref> or syndromes.<ref name="O'Brien&Yule19952">{{Cite book |title=Behavioural Phenotype |publisher=Mac Keith Press |year=1995 |isbn=978-1-898683-06-3 |series=Clinics in Developmental Medicine No.138 | veditors = O'Brien G, Yule W |place=London}}</ref><ref name="O'Brien20022">{{Cite book |url=https://books.google.com/books?id=flz27_U0AhgC&q=%22behavioural+phenotypes+in+clinical+practice%22 |title=Behavioural Phenotypes in Clinical Practice |publisher=Mac Keith Press |year=2002 |isbn=978-1-898683-27-8 | veditors = O'Brien G |place=London |access-date=27 September 2010}}</ref>

A '''phenome''' is the set of all traits expressed by a cell, tissue, organ, organism, or species. The term was first used by Davis in 1949, "We here propose the name ''phenome'' for the sum total of extragenic, non-autoreproductive portions of the cell, whether cytoplasmic or nuclear. The phenome would be the material basis of the phenotype, just as the genome is the material basis of the genotype."<ref>{{cite journal |author=Davis BD |title=The Isolation of Biochemically Deficient Mutants of Bacteria by Means of Penicillin |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=35 |issue=1 |pages=1–10 |date=January 1949 |pmid=16588845 |pmc=1062948 |doi= 10.1073/pnas.35.1.1|bibcode=1949PNAS...35....1D |doi-access=free }}</ref> Although phenome has been in use for many years, the distinction between the use of phenome and phenotype is problematic. A proposed definition for both terms as the "physical totality of all traits of an organism or of one of its subsystems" was put forth by Mahner and Kary in 1997, who argue that although scientists tend to intuitively use these and related terms in a manner that does not impede research, the terms are not well defined and usage of the terms is not consistent.<ref name="JTB1">{{cite journal |vauthors=Loeffler M, Bratke T, Paulus U, Li YQ, Potten CS |title=Clonality and life cycles of intestinal crypts explained by a state dependent stochastic model of epithelial stem cell organization |journal=Journal of Theoretical Biology |volume=186 |issue=1 |pages=41–54 |date=May 1997 |pmid=9176636 |doi=10.1006/jtbi.1996.0340 |bibcode=1997JThBi.186...41L }}</ref>

Some usages of the term suggest that the phenome of a given organism is best understood as a kind of matrix of data representing physical manifestation of phenotype. For example, discussions led by A. Varki among those who had used the term up to 2003 suggested the following definition: "The body of information describing an organism's phenotypes, under the influences of genetic and environmental factors".<ref>{{cite journal |vauthors=Varki A, Altheide TK |title=Comparing the human and chimpanzee genomes: searching for needles in a haystack |journal=Genome Research |volume=15 |issue=12 |pages=1746–58 |date=December 2005 |pmid=16339373 |doi=10.1101/gr.3737405 |doi-access=free}}</ref> Another team of researchers characterize "the human phenome <nowiki>[as]</nowiki> a multidimensional search space with several neurobiological levels, spanning the proteome, cellular systems (e.g., signaling pathways), neural systems and cognitive and behavioural phenotypes."<ref name="Neuroscience1">{{cite journal |vauthors=Siebner HR, Callicott JH, Sommer T, Mattay VS |title=From the genome to the phenome and back: linking genes with human brain function and structure using genetically informed neuroimaging |journal=Neuroscience |volume=164 |issue=1 |pages=1–6 |date=November 2009 |pmid=19751805 |doi=10.1016/j.neuroscience.2009.09.009 |pmc=3013363}}</ref> Plant biologists have begun to explore the phenome in the study of plant physiology.<ref name="tplants">{{Cite journal|last1=Furbank|first1=Robert T.|last2=Tester|first2=Mark|date=December 2011|title=Phenomics--technologies to relieve the phenotyping bottleneck|journal=Trends in Plant Science|volume=16|issue=12|pages=635–644|doi=10.1016/j.tplants.2011.09.005|issn=1878-4372|pmid=22074787 |bibcode=2011TPS....16..635F }}</ref> In 2009, a research team demonstrated the feasibility of identifying genotype–phenotype associations using electronic health records (EHRs) linked to DNA biobanks. They called this method phenome-wide association study (PheWAS).<ref>{{Cite journal|last1=Denny|first1=Joshua C.|last2=Ritchie|first2=Marylyn D.|last3=Basford|first3=Melissa A.|last4=Pulley|first4=Jill M.|last5=Bastarache|first5=Lisa|last6=Brown-Gentry|first6=Kristin|last7=Wang|first7=Deede|last8=Masys|first8=Dan R.|last9=Roden|first9=Dan M.|last10=Crawford|first10=Dana C.|date=2010-05-01|title=PheWAS: demonstrating the feasibility of a phenome-wide scan to discover gene-disease associations|journal=Bioinformatics|volume=26|issue=9|pages=1205–1210|doi=10.1093/bioinformatics/btq126|issn=1367-4811|pmc=2859132|pmid=20335276}}</ref>thumb|384x384px|Exploring relationships among phenotype, genotype and environment at different levels<ref name=":0">{{Cite journal |last1=Guo |first1=Tingting |last2=Li |first2=Xianran |title=Machine learning for predicting phenotype from genotype and environment |journal=Current Opinion in Biotechnology |date=2023 |language=en |volume=79 |article-number=102853 |doi=10.1016/j.copbio.2022.102853|pmid=36463837 |s2cid=254211407 |doi-access=free }}</ref> Inspired by the evolution from genotype to genome to pan-genome, a concept of eventually exploring the relationship among pan-phenome, pan-genome, and pan-envirome was proposed in 2023.<ref name=":0" />

[[File:Biston.betularia.7200.jpg|thumb|''Biston betularia'' morpha ''typica'', the standard light-colored peppered moth]] thumb|''B.betularia'' morpha ''carbonaria'', the melanic form, illustrating discontinuous variation

==Phenotypic variation== {{See also|Ecophenotypic variation}} Phenotypic variation is a fundamental prerequisite for evolution by natural selection. Not all phenotypic variation is caused by underlying heritable genetic variation. This is because the organization of living things is 'plastic', as Darwin emphasized, or 'readily capable of change.'<ref>{{cite book |last=Darwin |first=Charles |year=1872 |title=The Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life |pages=112–115, 438 |url=http://darwin-online.org.uk/content/frameset?pageseq=1&itemID=F391&viewtype=side |edition=6th |location=London |publisher=John Murray |oclc=1185571 }}</ref> It is the living organism as a whole that interacts with the environment and so contributes (or not) to the next generation. Thus, natural selection affects the genetic structure of a population ''indirectly'' via the contribution of phenotypes. Without phenotypic variation, there would be no evolution by natural selection.<ref name="Lewontin70">{{cite journal | vauthors = Lewontin RC |author-link=Richard Lewontin |date=November 1970 |title=The Units of Selection |url=http://joelvelasco.net/teaching/167/lewontin%2070%20-%20the%20units%20of%20selection.pdf |journal=Annual Review of Ecology and Systematics |volume=1 |issue=1 |pages=1–18 |doi=10.1146/annurev.es.01.110170.000245 |jstor=2096764|bibcode=1970AnRES...1....1L |s2cid=84684420 }}</ref>

The interaction between genotype and phenotype has often been conceptualized without reference to living organisms, as in the following relationship:

:genotype (G) + environment (E) → phenotype (P)

But a genotype can only be affected by or affect the environment insofar as it is embodied in a living organism. Hence, a more nuanced version of the relationship is:

:genotype (G) + organism & environment interactions (OE) → phenotype (P)

Phenotypes often show much flexibility or phenotypic plasticity in the expression of genotypes; in many organisms the phenotypes which 'express' a given genotype are very different under varying environmental conditions. The plant ''Hieracium umbellatum'' is found growing in two different habitats in Sweden. One habitat is rocky, sea-side cliffs, where the plants develop to be bushy with broad leaves and expanded inflorescences; the other is among sand dunes where the plants develop to lie prostrate with narrow leaves and compact inflorescences. The habitats alternate along the coast of Sweden and the habitat that seeds containing the identical genotype of ''Hieracium umbellatum'' land in, determines the phenotype which develops.<ref name=Botanyonline>{{cite web | vauthors = von Sengbusch P |url=http://www.biologie.uni-hamburg.de/b-online/e37/37b.htm |title= Phenotypic and Genetic Variation; Ecotypes | work = Botany online: Evolution: The Modern Synthesis - Phenotypic and Genetic Variation; Ecotypes |access-date=2009-12-29 |archive-url=https://web.archive.org/web/20090618051236/http://www.biologie.uni-hamburg.de/b-online/e37/37b.htm |archive-date=2009-06-18 }}</ref>

An example of random variation in ''Drosophila'' flies is the number of ommatidia, which may vary (randomly) between left and right eyes in a single individual as much as they do between different genotypes overall, or between clones raised in different environments.<ref>{{Cite book |last=Lewontin |first=Richard |title=The Triple Helix: Gene, Organism, and Environment |date=April 2000 |publisher=Harvard University Press}}</ref>

The concept of phenotype can be extended to variations below the level of the gene which affect an organism's fitness. For example, silent mutations that do not change the corresponding amino acid sequence of a gene may change the frequency of guanine-cytosine base pairs (GC content). The base pairs have a higher thermal stability (''melting point'') than adenine-thymine, a property that might convey, among organisms living in high-temperature environments, a selective advantage on variants enriched in GC content.{{citation needed|date=March 2018}}

===The extended phenotype=== {{main |The Extended Phenotype}}

Richard Dawkins described a phenotype that included all effects that a gene has on its surroundings, including other organisms, as an extended phenotype, arguing that "An animal's behavior tends to maximize the survival of the genes 'for' that behavior, whether or not those genes happen to be in the body of the particular animal performing it."<ref name=r1>{{cite journal | vauthors = Dawkins R | title = Replicator selection and the extended phenotype | journal = Zeitschrift für Tierpsychologie | volume = 47 | issue = 1 | pages = 61–76 | date = May 1978 | pmid = 696023 | doi = 10.1111/j.1439-0310.1978.tb01823.x | author-link = Richard Dawkins }}</ref> For instance, an organism such as a beaver modifies its environment by building a beaver dam; this can be considered an expression of its genes, just as its incisor teeth are—which it uses to modify its environment. Similarly, when a bird feeds a brood parasite such as a cuckoo, it is unwittingly extending its phenotype; and when genes in an orchid affect orchid bee behavior to increase pollination, or when genes in a peacock affect the copulatory decisions of peahens, again, the phenotype is being extended. Genes are, in Dawkins's view, selected by their phenotypic effects.<ref>{{Cite book | vauthors = Dawkins R |author-link=Richard Dawkins |title=The Extended Phenotype |publisher=Oxford University |year=1982 |page=[https://archive.org/details/extendedphenotyp0000dawk/page/4 4] |isbn=978-0-19-288051-2 |url=https://archive.org/details/extendedphenotyp0000dawk/page/4 }}</ref>

Other biologists broadly agree that the extended phenotype concept is relevant, but consider that its role is largely explanatory, rather than assisting in the design of experimental tests.<ref name="Hunter2009">{{cite journal | vauthors = Hunter P | title = Extended phenotype redux. How far can the reach of genes extend in manipulating the environment of an organism? | journal = EMBO Reports | volume = 10 | issue = 3 | pages = 212–215 | date = March 2009 | pmid = 19255576 | pmc = 2658563 | doi = 10.1038/embor.2009.18 }}</ref>

== Genes and phenotypes == thumb|An organism's phenotype is determined by the sum of its genetic material along with the influence of its environment. This is mediated by a range of biological mechanisms: either the direct activities of gene products or their downstream effects.<ref>{{Cite book |last1=Pakay |first1=Julian |title=Threshold Concepts in Biochemistry |last2=Duivenvoorden |first2=Hendrika |last3=Shafee |first3=Thomas |last4=Clarke |first4=Kaitlin |publisher=La Trobe eBureau |year=2023 |isbn=978-0-6484681-9-6 |doi=10.26826/1017|s2cid=258899183 }}</ref> Phenotypes develop through an interaction of genes and their immediate cellular environment, the cellular environment being under the influence of the host-organism's interaction with ''its'' environment. Thus there is a multiplicity of ways that genes and phenotypes interact. Most simply, for example, we might say an albino phenotype develops as a consequence of a mutation in the gene encoding tyrosinase which is a key enzyme in melanin formation. Even here, however, exposure to UV radiation can increase melanin production, hence the environment plays a role in this phenotype as well. For most complex phenotypes the precise genetic mechanism remains unknown. {{cn|date=August 2025}}

Gene expression plays a crucial role in determining the phenotypes of organisms. The level of gene expression can affect the phenotype of an organism. For example, if a gene that codes for a particular enzyme is expressed at high levels, the organism may produce more of that enzyme and exhibit a particular trait as a result. On the other hand, if the gene is expressed at low levels, the organism may produce less of the enzyme and exhibit a different trait.<ref>{{cite journal |last1=Oellrich |first1=A. |author2=Sanger Mouse Genetics Project |last3=Smedley |first3=D. |title=Linking tissues to phenotypes using gene expression profiles |journal=Database |date=2014 |volume=2014 |article-number=bau017 |doi=10.1093/database/bau017|pmid=24634472 |pmc=3982582 }}</ref> Gene expression is regulated at various levels and thus each level can affect certain phenotypes, including transcriptional and post-transcriptional regulation.{{cn|date=May 2024}}

thumb|right|alt=tortoiseshell cat|The patchy colors of a tortoiseshell cat are the result of different levels of expression of pigmentation genes in different areas of the skin.

Changes in the levels of gene expression can be influenced by a variety of factors, such as environmental conditions, genetic variations, and epigenetic modifications. These modifications can be influenced by environmental factors such as diet, stress, and exposure to toxins, and can have a significant impact on an individual's phenotype. Some phenotypes may be the result of changes in gene expression due to these factors, rather than changes in genotype. An experiment involving machine learning methods utilizing gene expressions measured from RNA sequencing found that they can contain enough signal to separate individuals in the context of phenotype prediction.<ref>{{cite journal |last1=Nussinov |first1=Ruth |last2=Tsai |first2=Chung-Jung |last3=Jang |first3=Hyunbum |title=Protein ensembles link genotype to phenotype |journal=PLOS Computational Biology |date=2019 |volume=15 |issue=6 |article-number=e1006648 |doi=10.1371/journal.pcbi.1006648|pmid=31220071 |pmc=6586255 |bibcode=2019PLSCB..15E6648N |doi-access=free }}</ref>

== Phenome and phenomics == {{distinguish |Phoneme |Phonology}} Although a phenotype is the ensemble of observable characteristics displayed by an organism, the word ''phenome'' is sometimes used to refer to a collection of traits, while the simultaneous study of such a collection is referred to as ''phenomics''.<ref>{{cite journal | vauthors = Mahner M, Kary M | title = What exactly are genomes, genotypes and phenotypes? And what about phenomes? | journal = Journal of Theoretical Biology | volume = 186 | issue = 1 | pages = 55–63 | date = May 1997 | pmid = 9176637 | doi = 10.1006/jtbi.1996.0335 | name-list-style = amp | bibcode = 1997JThBi.186...55M | doi-access = free }}</ref><ref>{{cite journal | vauthors = Varki A, Wills C, Perlmutter D, Woodruff D, Gage F, Moore J, Semendeferi K, Bernirschke K, Katzman R, Doolittle R, Bullock T | display-authors = 6 | title = Great Ape Phenome Project? | journal = Science | volume = 282 | issue = 5387 | pages = 239–240 | date = October 1998 | pmid = 9841385 | doi = 10.1126/science.282.5387.239d | s2cid = 5837659 | bibcode = 1998Sci...282..239V }}</ref> Phenomics is an important field of study because it can be used to figure out which genomic variants affect phenotypes which then can be used to explain things like health, disease, and evolutionary fitness.<ref>{{cite journal | vauthors = Houle D, Govindaraju DR, Omholt S | title = Phenomics: the next challenge | journal = Nature Reviews Genetics | volume = 11 | issue = 12 | pages = 855–866 | date = December 2010 | pmid = 21085204 | doi = 10.1038/nrg2897 | s2cid = 14752610 }}</ref> Phenomics forms a large part of the Human Genome Project.<ref>{{cite journal | vauthors = Freimer N, Sabatti C | title = The human phenome project | journal = Nature Genetics | volume = 34 | issue = 1 | pages = 15–21 | date = May 2003 | pmid = 12721547 | doi = 10.1038/ng0503-15 | s2cid = 31510391 }}</ref>

Phenomics has applications in agriculture. For instance, genomic variations such as drought and heat resistance can be identified through phenomics to create more durable GMOs.<ref>{{Cite book | vauthors = Rahman H, Ramanathan V, Jagadeeshselvam N, Ramasamy S, Rajendran S, Ramachandran M, Sudheer PD, Chauhan S, Natesan S, Muthurajan R | chapter = Phenomics: Technologies and Applications in Plant and Agriculture | display-authors = 6 |title=PlantOmics: The Omics of Plant Science |date=2015-01-01 |publisher=Springer | location = New Delhi |isbn=978-81-322-2171-5 |pages=385–411 |doi=10.1007/978-81-322-2172-2_13 | veditors = Barh D, Khan MS, Davies E }}</ref><ref name="tplants"/> Phenomics may be a stepping stone towards personalized medicine, particularly drug therapy.<ref name="monte">{{cite journal | vauthors = Monte AA, Brocker C, Nebert DW, Gonzalez FJ, Thompson DC, Vasiliou V | title = Improved drug therapy: triangulating phenomics with genomics and metabolomics | journal = Human Genomics | volume = 8 | issue = 1 | page = 16 | date = September 2014 | pmid = 25181945 | pmc = 4445687 | doi = 10.1186/s40246-014-0016-9 | author3-link = Daniel W. Nebert | doi-access = free }}</ref> Once the phenomic database has acquired enough data, a person's phenomic information can be used to select specific drugs tailored to the individual.<ref name="monte" />

==Large-scale phenotyping and genetic screens== {{See also|Genetic screen|Essential gene}}

Large-scale genetic screens can identify the genes or mutations that affect the phenotype of an organism. Analyzing the phenotypes of mutant genes can also aid in determining gene function.<ref>{{cite journal | vauthors = Amsterdam A, Burgess S, Golling G, Chen W, Sun Z, Townsend K, Farrington S, Haldi M, Hopkins N | display-authors = 6 | title = A large-scale insertional mutagenesis screen in zebrafish | journal = Genes & Development | volume = 13 | issue = 20 | pages = 2713–2724 | date = October 1999 | pmid = 10541557 | pmc = 317115 | doi = 10.1101/gad.13.20.2713 }}</ref> Most genetic screens have used microorganisms, in which genes can be easily deleted. For instance, nearly all genes have been deleted in ''E. coli''<ref>{{cite journal | vauthors = Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H | display-authors = 6 | title = Construction of ''Escherichia coli'' K-12 in-frame, single-gene knockout mutants: the Keio collection | journal = Molecular Systems Biology | volume = 2 | issue = 1 | article-number = 2006.0008 | date = January 2006 | pmid = 16738554 | pmc = 1681482 | doi = 10.1038/msb4100050 }}</ref> and many other bacteria, but also in several eukaryotic model organisms such as baker's yeast<ref>{{cite journal | vauthors = Nislow C, Wong LH, Lee AH, Giaever G | title = Functional genomics using the ''Saccharomyces cerevisiae'' yeast deletion collections | journal = Cold Spring Harbor Protocols | volume = 2016 | issue = 9 | article-number = pdb.top080945 | date = September 2016 | pmid = 27587784 | doi = 10.1101/pdb.top080945 }}</ref> and fission yeast.<ref>{{cite journal | vauthors = Kim DU, Hayles J, Kim D, Wood V, Park HO, Won M, Yoo HS, Duhig T, Nam M, Palmer G, Han S, Jeffery L, Baek ST, Lee H, Shim YS, Lee M, Kim L, Heo KS, Noh EJ, Lee AR, Jang YJ, Chung KS, Choi SJ, Park JY, Park Y, Kim HM, Park SK, Park HJ, Kang EJ, Kim HB, Kang HS, Park HM, Kim K, Song K, Song KB, Nurse P, Hoe KL | display-authors = 6 | title = Analysis of a genome-wide set of gene deletions in the fission yeast ''Schizosaccharomyces pombe'' | journal = Nature Biotechnology | volume = 28 | issue = 6 | pages = 617–623 | date = June 2010 | pmid = 20473289 | pmc = 3962850 | doi = 10.1038/nbt.1628 | bibcode = 2010NatBi..28..617K }}</ref> Among other discoveries, such studies have revealed lists of essential genes. {{cn|date=August 2025}}

More recently, large-scale phenotypic screens have also been used in animals, e.g., to study lesser understood phenotypes such as behavior. In one screen, the role of mutations in mice were studied in areas including learning and memory, circadian rhythmicity, vision, responses to stress, and response to psychostimulants. {{cn|date=August 2025}} {| class="wikitable" |+Large-scale mutagenesis and phenotypic screens for the nervous system and behavior in mice !Phenotypic domain !Assay !Notes !Software package |- |Circadian Rhythm |Wheel running behavior | |ClockLab |- |Learning and Memory |Fear conditioning |Video-image-based scoring of freezing |FreezeFrame |- |Preliminary Assessment |Open field activity and elevated plus maze |Video-image-based scoring of exploration |LimeLight |- |Psychostimulant response |Hyperlocomotion behavior |Video-image-based tracking of locomotion |BigBrother |- |Vision |Electroretinogram and Fundus photography | |L. Pinto and colleagues |} This experiment involves the progeny of mice treated with ENU, or N-ethyl-N-nitrosourea, which is a potent mutagen that causes point mutations. The mice were phenotypically screened for alterations in the different behavioral domains in order to find the number of putative mutants (see table for details). Putative mutants are then tested for heritability in order to help determine the inheritance pattern as well as map out the mutations. Once they have been mapped out, cloned, and identified, it can be determined whether a mutation represents a new gene or not. {{cn|date=August 2025}} {| class="wikitable" !Phenotypic domain !ENU progeny screened !Putative mutants !Putative mutant lines with progeny !Confirmed mutants |- |General assessment |29860 |80 |38 |14 |- |Learning and memory |23123 |165 |106 |19 |- |Psychostimulant response |20997 |168 |86 |9 |- |Neuroendocrine response to stress |13118 |126 |54 |2 |- |Vision |15582 |108 |60 |6 |} These experiments show that mutations in the rhodopsin gene affected vision and can even cause retinal degeneration in mice.<ref>{{cite journal | vauthors = Vitaterna MH, Pinto LH, Takahashi JS | title = Large-scale mutagenesis and phenotypic screens for the nervous system and behavior in mice | language = English | journal = Trends in Neurosciences | volume = 29 | issue = 4 | pages = 233–240 | date = April 2006 | pmid = 16519954 | pmc = 3761413 | doi = 10.1016/j.tins.2006.02.006 }}</ref> The same amino acid change causes human familial blindness, showing how phenotyping in animals can inform medical diagnostics and possibly therapy.

==Evolutionary origin of phenotype== The RNA world is the hypothesized pre-cellular stage in the evolutionary history of life on earth, in which self-replicating RNA molecules proliferated prior to the evolution of DNA and proteins.<ref name = Michod1983>{{cite journal | vauthors = Michod RE | title = Population biology of the first replicators: on the origin of the genotype, phenotype and organism. | journal = American Zoologist | date = February 1983 | volume = 23 | issue = 1 | pages = 5–14 | doi = 10.1093/icb/23.1.5 | doi-access = free }}</ref> The folded three-dimensional physical structure of the first RNA molecule that possessed ribozyme activity promoting replication while avoiding destruction would have been the first phenotype, and the nucleotide sequence of the first self-replicating RNA molecule would have been the original genotype.<ref name = Michod1983/>

== References == {{Reflist|30em}}

== External links == {{Commons category |Phenotypes}} {{wikt | phenotype}} * [http://www.jax.org/phenome Mouse Phenome Database] * [http://www.human-phenotype-ontology.org Human Phenotype Ontology] * [https://web.archive.org/web/20070426154232/http://www.europhenome.org/ Europhenome: Access to raw and annotated mouse phenotype data] * [http://embryo.asu.edu/handle/10776/4206/ "Wilhelm Johannsen's Genotype-Phenotype Distinction" by E. Peirson at the Embryo Project Encyclopedia] * [https://web.archive.org/web/20060909075405/http://phenome.jax.org/pub-cgi/phenome/mpdcgi?rtn=docs%2Fhome Mouse Phenome Project] at the Jackson Laboratory

Category:Classical genetics Category:Polymorphism (biology)