Gene nomenclature is the scientificnaming ofgenes, the units ofheredity in living organisms. It is also closely associated withprotein nomenclature, as genes and the proteins they code for usually have similar nomenclature. An international committee published recommendations for genetic symbols and nomenclature in 1957.[1] The need to develop formal guidelines for human gene names and symbols was recognized in the 1960s and full guidelines were issued in 1979 (Edinburgh Human Genome Meeting).[2] Several othergenus-specific research communities (e.g.,Drosophila fruit flies,Mus mice) have adopted nomenclature standards, as well, and have published them on the relevantmodel organism websites and in scientific journals, including theTrends in Genetics Genetic Nomenclature Guide.[3][4] Scientists familiar with a particulargene family may work together to revise the nomenclature for the entire set of genes when new information becomes available.[5] For many genes and their corresponding proteins, an assortment of alternate names is in use across the scientific literature and publicbiological databases, posing a challenge to effective organization and exchange of biological information.[6]Standardization of nomenclature thus tries to achieve the benefits ofvocabulary control andbibliographic control, although adherence is voluntary. The advent of theinformation age has broughtgene ontology, which in some ways is a next step of gene nomenclature, because it aims to unify the representation of gene and gene product attributes across all species.
Gene nomenclature andprotein nomenclature are not separate endeavors; they are aspects of the same whole. Any name or symbol used for a protein can potentially also be used for the gene that encodes it, and vice versa.[citation needed] But owing to the nature of how science has developed (with knowledge being uncovered bit by bit over decades), proteins and their corresponding genes have not always been discovered simultaneously (and not always physiologically understood when discovered), which is the largest reason why protein and gene names do not always match, or why scientists tend to favor one symbol or name for the protein and another for the gene.[citation needed] Another reason is that many of the mechanisms of life are the same or very similar acrossspecies, genera, orders, and phyla (throughhomology, analogy, or some of both), so that a given protein may be produced in many kinds of organisms; and thus scientists naturally often use the same symbol and name for a given protein in one species (for example, mice) as in another species (for example, humans). Regarding the first duality (same symbol and name for gene or protein), the context usually makes the sense clear to scientific readers, and the nomenclatural systems also provide for some specificity by usingitalic for a symbol when the gene is meant and plain (roman) for when the protein is meant.[citation needed] Regarding the second duality (a given protein isendogenous in many kinds of organisms), the nomenclatural systems also provide for at least human-versus-nonhuman specificity by using differentcapitalization,[citation needed] although scientists often ignore this distinction, given that it is often biologically irrelevant.[citation needed]
Also owing to the nature of how scientific knowledge has unfolded, proteins and their corresponding genes often have several names and symbols that aresynonymous. Some of the earlier ones may bedeprecated in favor of newer ones, although such deprecation is voluntary. Some older names and symbols live on simply because they have been widely used in thescientific literature (including before the newer ones were coined) and are well established among users. For example,mentions ofHER2 andERBB2 are synonymous.
Lastly, the correlation between genes and proteins is not alwaysone-to-one (in either direction); in some cases it is several-to-one or one-to-several, and the names and symbols may then be gene-specific or protein-specific to some degree, or overlapping in usage:
TheHUGO Gene Nomenclature Committee is responsible for providing human gene naming guidelines and approving new, unique human gene names and symbols (shortidentifiers typically created by abbreviating). For some nonhuman species, model organism databases serve as central repositories of guidelines and help resources, including advice fromcurators and nomenclature committees. In addition to species-specific databases, approved gene names and symbols for many species can be located in theNational Center for Biotechnology Information's "Entrez Gene"[7] database.
There are generally accepted rules and conventions used for naminggenes inbacteria. Standards were proposed in 1966 by Demerec et al.[8]
Each bacterial gene is denoted by amnemonic of three lower case letters which indicate the pathway or process in which the gene-product is involved, followed by a capital letter signifying the actual gene. In some cases, the gene letter may be followed by anallele number. All letters and numbers are underlined or italicised. For example,leuA is one of the genes of theleucine biosynthetic pathway, andleuA273 is a particular allele of this gene.
Where the actual protein coded by the gene is known then it may become part of the basis of the mnemonic, thus:
Some gene designations refer to a known general function:
In a 1998 analysis of theE. coli genome, a large number of genes with unknown function were designated names beginning with the lettery, followed by sequentially generated letters without a mnemonic meaning (e.g.,ydiO andydbK).[9] Since being designated, somey-genes have been confirmed to have a function,[10] and assigned a synonym (alternative) name in recognition of this. However, as y-genes are not always re-named after being further characterised, this designation is not a reliable indicator of a gene's significance.[10]
Loss of gene activity leads to a nutritional requirement (auxotrophy) not exhibited by thewildtype (prototrophy).
Amino acids:
Some pathways produce metabolites that are precursors of more than one pathway. Hence, loss of one of these enzymes will lead to a requirement for more than one amino acid. For example:
Nucleotides:
Vitamins:
Loss of gene activity leads to loss of the ability to catabolise (use) the compound.
If the gene in question is the wildtype a superscript '+' sign is used:
If a gene is mutant, it is signified by a superscript '-':
By convention, if neither is used, it is considered to be mutant.
There are additional superscripts and subscripts which provide more information about the mutation:
Other modifiers:
When referring to the genotype (the gene) the mnemonic is italicized and not capitalised. When referring to the gene product or phenotype, the mnemonic is first-letter capitalised and not italicized (e.g. DnaA – the protein produced by thednaA gene; LeuA− – the phenotype of aleuA mutant; AmpR – the ampicillin-resistance phenotype of the β-lactamase genebla).
Protein names are generally the same as the gene names, but the protein names are not italicized, and the first letter is upper-case. E.g. the name ofRNApolymerase is RpoB, and this protein is encoded byrpoB gene.[11]
| Gene and protein symbol conventions ("sonic hedgehog" gene) | ||
| Species | Gene symbol | Protein symbol |
|---|---|---|
| Homo sapiens | SHH | SHH |
| Mus musculus,Rattus norvegicus | Shh | SHH |
| Gallus gallus | SHH | SHH |
| Anolis carolinensis | shh | SHH |
| Xenopus laevis,X. tropicalis | shh | Shh |
| Danio rerio | shh | Shh |
The research communities ofvertebrate model organisms have adopted guidelines whereby genes in these species are given, whenever possible, the same names as their humanorthologs. The use of prefixes on gene symbols to indicate species (e.g., "Z" for zebrafish) is discouraged. The recommended formatting of printed gene and protein symbols varies between species.
Vertebrate genes and proteins have names (typically strings of words) and symbols, which are shortidentifiers (typically 3 to 8 characters). For example, the genecytotoxic T-lymphocyte-associated protein 4 has the HGNC symbolCTLA4. These symbols are usually, but not always, coined bycontraction oracronymic abbreviation of the name. They arepseudo-acronyms, however, in the sense that they are complete identifiers by themselves—short names, essentially. They are synonymous with (rather than standing for) the gene/protein name (or any of its aliases), regardless of whether the initial letters "match". For example, the symbol for the gene v-akt murine thymoma viral oncogene homolog 1, which isAKT1, cannot be said to be an acronym for the name, and neither can any of its various synonyms, which includeAKT,PKB,PRKBA, andRAC. Thus, the relationship of a gene symbol to the gene name is functionally the relationship of anickname to a formal name (both are completeidentifiers)—it is not the relationship of an acronym to its expansion. In this sense they are similar to the symbols forunits of measurement in the SI system (such as km for thekilometre), in that they can be viewed as truelogograms rather than just abbreviations. Sometimes the distinction is academic, but not always. Although it is not wrong to say that "VEGFA" is an acronym standing for "vascular endothelial growth factor A", just as it is not wrong that "km" is an abbreviation for "kilometre", there is more to the formality of symbols than those statements capture.
Theroot portion of the symbols for agene family (such as the "SERPIN" root inSERPIN1,SERPIN2,SERPIN3, and so on) is called a root symbol.[12]
TheHUGO Gene Nomenclature Committee is responsible for providing human gene naming guidelines and approving new, unique human gene names and symbols (shortidentifiers typically created by abbreviating). All human gene names and symbols can be searched online at the HGNC[13] website, and the guidelines for their formation are available there.[14] The guidelines for humans fit logically into the larger scope ofvertebrates in general, and the HGNC's remit has recently expanded to assigning symbols to all vertebrate species without an existing nomenclature committee, to ensure that vertebrate genes are named in line with their human orthologs/paralogs. Human gene symbols generally are italicised, with all letters in uppercase (e.g.,SHH, forsonic hedgehog). Italics are not necessary in gene catalogs. Protein designations are the same as the gene symbol except that they are not italicised. Like the gene symbol, they are inall caps because human (human-specific or human homolog). mRNAs and cDNAs use the same formatting conventions as the gene symbol.[5] For namingfamilies of genes, the HGNC recommends using a "root symbol"[15] as the root for the various gene symbols. For example, for theperoxiredoxin family,PRDX is the root symbol, and the family members arePRDX1,PRDX2,PRDX3,PRDX4,PRDX5, andPRDX6.
Gene symbols generally are italicised, with only the first letter in uppercase and the remaining letters in lowercase (Shh). Italics are not required on web pages. Protein designations are the same as the gene symbol, but are not italicised and all are upper case (SHH).[16]
Nomenclature generally follows the conventions of human nomenclature. Gene symbols generally are italicised, with all letters in uppercase (e.g.,NLGN1, for neuroligin1). Protein designations are the same as the gene symbol, but are not italicised; all letters are in uppercase (NLGN1). mRNAs and cDNAs use the same formatting conventions as the gene symbol.[17]
Gene symbols are italicised and all letters are in lowercase (shh). Protein designations are different from their gene symbol; they are not italicised, and all letters are in uppercase (SHH).[18]
Gene symbols are italicised and all letters are in lowercase (shh). Protein designations are the same as the gene symbol, but are not italicised; the first letter is in uppercase and the remaining letters are in lowercase (Shh).[19]
Gene symbols are italicised, with all letters in lowercase (shh). Protein designations are the same as the gene symbol, but are not italicised; the first letter is in uppercase and the remaining letters are in lowercase (Shh).[20]
A nearly universal rule in copyediting of articles formedical journals and other health science publications is that abbreviations and acronyms must beexpanded at first use, to provide aglossing type of explanation. Typically no exceptions are permitted except for small lists of especially well known terms (such asDNA orHIV). Although readers with highsubject-matter expertise do not need most of these expansions, those with intermediate or (especially) low expertise are appropriately served by them.
One complication that gene and protein symbols bring to this general rule is that they are not, accurately speaking, abbreviations or acronyms, despite the fact that many were originally coined via abbreviating or acronymic etymology. They arepseudoacronyms (asSAT andKFC also are) because they do not "stand for" any expansion. Rather, the relationship of a gene symbol to the gene name is functionally the relationship of anickname to a formal name (both are completeidentifiers)—it is not the relationship of an acronym to its expansion. In fact, many official gene symbol–gene name pairs do not even share their initial-letter sequences (although some do). Nevertheless, gene and protein symbols "look just like" abbreviations and acronyms, which presents the problem that "failing" to "expand" them (even though it is not actually a failure and there are no true expansions) creates the appearance of violating the spell-out-all-acronyms rule.
One common way of reconciling these two opposing forces is simply to exempt all gene and protein symbols from the glossing rule. This is certainly fast and easy to do, and in highly specialized journals, it is also justified because the entire targetreadership has high subject matter expertise. (Experts are not confused by the presence of symbols (whether known or novel) and they know where to look them up online for further details if needed.) But for journals with broader and more general target readerships, this action leaves the readers without anyexplanatory annotation and can leave them wondering what the apparent-abbreviation stands for and why it was not explained. Therefore, a good alternative solution is simply to put either the official gene name or a suitable short description (gene alias/other designation) in parentheses after the first use of the official gene/protein symbol. This meets both the formal requirement (the presence of a gloss) and the functional requirement (helping the reader to know what the symbol refers to). The same guideline applies to shorthand names for sequence variations;AMA says, "In general medical publications, textual explanations should accompany the shorthand terms at first mention."[21] Thus "188del11" is glossed as "an 11-bp deletion at nucleotide 188." This corollary rule (which forms an adjunct to the spell-everything-out rule) often also follows the "abbreviation-leading" style of expansion that is becoming more prevalent in recent years. Traditionally, the abbreviation always followed the fully expanded form in parentheses at first use. This is still the general rule. But for certain classes of abbreviations or acronyms (such asclinical trial acronyms [e.g.,ECOG] or standardized polychemotherapy regimens [e.g.,CHOP]), this pattern may be reversed, because the short form is more widely used and the expansion is merely parenthetical to the discussion at hand. The same is true of gene/protein symbols.
TheHUGO Gene Nomenclature Committee (HGNC) maintains an official symbol and name for each human gene, as well as a list of synonyms and previous symbols and names. For example, forAFF1 (AF4/FMR2 family, member 1), previous symbols and names areMLLT2 ("myeloid/lymphoid or mixed-lineage leukemia (trithorax (Drosophila) homolog); translocated to, 2") andPBM1 ("pre-B-cell monocytic leukemia partner 1"), and synonyms areAF-4 andAF4. Authors of journal articles often use the latest official symbol and name, but just as often they use synonyms and previous symbols and names, which are well established by earlier use in the literature. AMA style is that "authors should use the most up-to-date term"[22] and that "in any discussion of a gene, it is recommended that the approved gene symbol be mentioned at some point, preferably in the title and abstract if relevant."[22] Because copyeditors are not expected or allowed to rewrite the gene and protein nomenclature throughout a manuscript (except by rare express instructions on particular assignments), the middle ground in manuscripts using synonyms or older symbols is that the copyeditor will add a mention of the current official symbol at least as a parenthetical gloss at the first mention of the gene or protein, and query for confirmation.
Some basic conventions, such as (1) that animal/human homolog (ortholog) pairs differ inletter case (title case andall caps, respectively) and (2) that the symbol is italicized when referring to the gene but nonitalic when referring to the protein, are often not followed by contributors to medical journals. Many journals have the copyeditors restyle the casing and formatting to the extent feasible, although in complex genetics discussions onlysubject-matter experts (SMEs) can effortlessly parse them all. One example that illustrates the potential for ambiguity among non-SMEs is that some official gene names have the word "protein" within them, so the phrase "brain protein I3 (BRI3)" (referring to the gene) and "brain protein I3 (BRI3)" (referring to the protein) are both valid. TheAMA Manual gives another example: both "the TH gene" and "theTH gene" can validly be parsed as correct ("the gene for tyrosine hydroxylase"), because the first mentions the alias (description) and the latter mentions the symbol. This seems confusing on the surface, although it is easier to understand when explained as follows: in this gene's case, as in many others, the alias (description) "happens to use the same letter string" that the symbol uses. (The matching of the letters is of course acronymic in origin and thus the phrase "happens to" implies more coincidence than is actually present; but phrasing it that way helps to make the explanation clearer.) There is no way for a non-SME to know this is the case for any particular letter string without looking up every gene from the manuscript in a database such as NCBI Gene, reviewing its symbol, name, and alias list, and doing some mental cross-referencing and double-checking (plus it helps to have biochemical knowledge). Most medical journals do not (in some cases cannot) pay for that level offact-checking as part of their copyediting service level; therefore, it remains the author's responsibility. However, as pointed out earlier, many authors make little attempt to follow the letter case or italic guidelines; and regarding protein symbols, they often will not use the official symbol at all. For example, although the guidelines would callp53 protein "TP53" in humans or "Trp53" in mice, most authors call it "p53" in both (and even refuse to call it "TP53" if edits or queries try to), not least because of the biologic principle that many proteins are essentially or exactly the same molecules regardless of mammalian species. Regarding the gene, authors are usually willing to call it by its human-specific symbol and capitalization,TP53, and may even do so without being prompted by a query. But the end result of all these factors is that the published literature often does not follow the nomenclature guidelines completely.
Bacteria: Gene symbols are typically composed of three lower-case, italicized letters that serve as an abbreviation of the process or pathway in which the gene product is involved (e.g.,rpo genes encodeRNApolymerase). To distinguish among different alleles, the abbreviation is followed by an upper-case letter (e.g., therpoB gene encodes the β subunit of RNA polymerase). Protein symbols are not italicized, and the first letter is upper-case (e.g., RpoB).