Editing Genetics (section)

== Gene expression ==

=== Genetic code ===
{{Main|Genetic code}}

[[File:Genetic code.svg|class=skin-invert-image|thumb|left|upright=1.3|The [[genetic code]]: Using a [[Genetic code#Discovery|triplet code]], DNA, through a [[messenger RNA]] intermediary, specifies a protein.]]

Genes [[Gene expression|express]] their functional effect through the production of proteins, which are molecules responsible for most functions in the cell. Proteins are made up of one or more polypeptide chains, each composed of a sequence of [[amino acid]]s. The DNA sequence of a gene is used to produce a specific [[Protein primary structure|amino acid sequence]]. This process begins with the production of an RNA molecule with a sequence matching the gene's DNA sequence, a process called [[Transcription (genetics)|transcription]].

This [[messenger RNA]] molecule then serves to produce a corresponding amino acid sequence through a process called [[translation (biology)|translation]]. Each group of three nucleotides in the sequence, called a [[codon]], corresponds either to one of the twenty possible amino acids in a protein or an [[stop codon|instruction to end the amino acid sequence]]; this correspondence is called the [[genetic code]].<ref>{{cite book |title=Biochemistry |vauthors=Berg JM, Tymoczko JL, Stryer L, Clarke ND |edition=5th |year=2002 |publisher=W.H. Freeman and Company |location=New York |chapter-url=https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=stryer.section.685 |chapter=I. 5. DNA, RNA, and the Flow of Genetic Information: Amino Acids Are Encoded by Groups of Three Bases Starting from a Fixed Point |url-status=live |archive-url=https://web.archive.org/web/20060411095303/http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=stryer.section.685 |archive-date=11 April 2006}}</ref> The flow of information is unidirectional: information is transferred from nucleotide sequences into the amino acid sequence of proteins, but it never transfers from protein back into the sequence of DNA—a phenomenon [[Francis Crick]] called the [[central dogma of molecular biology]].<ref name="crick1970">{{cite journal | vauthors = Crick F | title = Central dogma of molecular biology | journal = Nature | volume = 227 | issue = 5258 | pages = 561–563 | date = August 1970 | pmid = 4913914 | doi = 10.1038/227561a0 | url = http://www.nature.com/nature/focus/crick/pdf/crick227.pdf | url-status = live | s2cid = 4164029 | df = dmy-all | bibcode = 1970Natur.227..561C | archive-url = https://web.archive.org/web/20060215024341/http://www.nature.com/nature/focus/crick/pdf/crick227.pdf | archive-date = 15 February 2006 }}</ref>

The specific sequence of amino acids [[protein folding|results]] in a unique three-dimensional structure for that protein, and the three-dimensional structures of proteins are related to their functions.<ref>Alberts et al. (2002), [https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.section.388 I.3. Proteins: The Shape and Structure of Proteins] {{Webarchive|url=https://web.archive.org/web/20230101101721/https://www.ncbi.nlm.nih.gov/books/NBK26830/ |date=1 January 2023 }}</ref><ref>Alberts et al. (2002), [https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.section.452 I.3. Proteins: Protein Function] {{webarchive|url=https://web.archive.org/web/20060425162405/http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.section.452 |date=25 April 2006 }}</ref> Some are simple structural molecules, like the fibers formed by the protein [[collagen]]. Proteins can bind to other proteins and simple molecules, sometimes acting as [[enzyme]]s by facilitating [[chemical reaction]]s within the bound molecules (without changing the structure of the protein itself). Protein structure is dynamic; the protein [[hemoglobin]] bends into slightly different forms as it facilitates the capture, transport, and release of oxygen molecules within mammalian blood.{{cn|date=October 2022}}

A [[Single-nucleotide polymorphism|single nucleotide difference]] within DNA can cause a change in the amino acid sequence of a protein. Because protein structures are the result of their amino acid sequences, some changes can dramatically change the properties of a protein by destabilizing the structure or changing the surface of the protein in a way that changes its interaction with other proteins and molecules. For example, [[sickle-cell anemia]] is a human [[Genetic disorder|genetic disease]] that results from a single base difference within the [[coding region]] for the β-globin section of hemoglobin, causing a single amino acid change that changes hemoglobin's physical properties.<ref>{{cite web |title=How Does Sickle Cell Cause Disease? |url=http://sickle.bwh.harvard.edu/scd_background.html |date=11 April 2002 |access-date=23 July 2007 |publisher=Brigham and Women's Hospital: Information Center for Sickle Cell and Thalassemic Disorders |url-status=live |archive-url=https://web.archive.org/web/20100923165921/http://sickle.bwh.harvard.edu/scd_background.html |archive-date=23 September 2010}}</ref>
Sickle-cell versions of hemoglobin stick to themselves, stacking to form fibers that distort the shape of [[red blood cell]]s carrying the protein. These sickle-shaped cells no longer flow smoothly through [[blood vessel]]s, having a tendency to clog or degrade, causing the medical problems associated with this disease.<ref>{{Cite journal |last1=Elendu |first1=Chukwuka |last2=Amaechi |first2=Dependable C. |last3=Alakwe-Ojimba |first3=Chisom E. |last4=Elendu |first4=Tochi C. |last5=Elendu |first5=Rhoda C. |last6=Ayabazu |first6=Chiagozie P. |last7=Aina |first7=Titilayo O. |last8=Aborisade |first8=Ooreofe |last9=Adenikinju |first9=Joseph S. |date=2023-09-22 |title=Understanding Sickle cell disease: Causes, symptoms, and treatment options |journal=Medicine |language=en |volume=102 |issue=38 |pages=e35237 |doi=10.1097/MD.0000000000035237 |issn=0025-7974 |pmc=10519513 |pmid=37746969}}</ref>

Some DNA sequences are transcribed into RNA but are not translated into protein products—such RNA molecules are called [[non-coding RNA]]. In some cases, these products fold into structures which are involved in critical cell functions (e.g. [[ribosomal RNA]] and [[transfer RNA]]). RNA can also have regulatory effects through hybridization interactions with other RNA molecules (such as [[microRNA]]).<ref>{{Cite journal |last1=Marques |first1=Tânia Monteiro |last2=Gama-Carvalho |first2=Margarida |date=2022-02-19 |title=Network Approaches to Study Endogenous RNA Competition and Its Impact on Tissue-Specific microRNA Functions |journal=Biomolecules |language=en |volume=12 |issue=2 |pages=332 |doi=10.3390/biom12020332 |doi-access=free |pmid=35204832 |pmc=8868585 |issn=2218-273X }}</ref>

=== Nature and nurture ===
{{Main|Nature and nurture}}

[[File:Niobe050905-Siamese Cat.jpeg|thumb|upright|[[Siamese (cat)|Siamese cats]] have a temperature-sensitive pigment-production mutation.]]

Although genes contain all the information an organism uses to function, the environment plays an important role in determining the ultimate phenotypes an organism displays. The phrase "[[nature and nurture]]" refers to this complementary relationship. The phenotype of an organism depends on the interaction of genes and the environment. An interesting example is the coat coloration of the [[Siamese (cat)|Siamese cat]]. In this case, the body temperature of the cat plays the role of the environment. The cat's genes code for dark hair, thus the hair-producing cells in the cat make cellular proteins resulting in dark hair. But these dark hair-producing proteins are sensitive to temperature (i.e. have a mutation causing temperature-sensitivity) and [[Denaturation (biochemistry)|denature]] in higher-temperature environments, failing to produce dark-hair pigment in areas where the cat has a higher body temperature. In a low-temperature environment, however, the protein's structure is stable and produces dark-hair pigment normally. The protein remains functional in areas of skin that are colder—such as its legs, ears, tail, and face{{emdash}}so the cat has dark hair at its extremities.<ref>{{cite journal | vauthors = Imes DL, Geary LA, Grahn RA, Lyons LA | title = Albinism in the domestic cat (Felis catus) is associated with a tyrosinase (TYR) mutation | journal = Animal Genetics | volume = 37 | issue = 2 | pages = 175–178 | date = April 2006 | pmid = 16573534 | pmc = 1464423 | doi = 10.1111/j.1365-2052.2005.01409.x }}</ref>

Environment plays a major role in effects of the human genetic disease [[phenylketonuria]]. The mutation that causes phenylketonuria disrupts the ability of the body to break down the amino acid [[phenylalanine]], causing a toxic build-up of an intermediate molecule that, in turn, causes severe symptoms of progressive intellectual disability and seizures. However, if someone with the phenylketonuria mutation follows a strict diet that avoids this amino acid, they remain normal and healthy.<ref>{{cite web |url=https://www.nlm.nih.gov/medlineplus/phenylketonuria.html |title=MedlinePlus: Phenylketonuria |access-date=15 March 2008 |publisher=NIH: National Library of Medicine |url-status=live |archive-url=https://web.archive.org/web/20080725183720/http://www.nlm.nih.gov/medlineplus/phenylketonuria.html |archive-date=25 July 2008}}</ref>

A common method for determining how genes and environment ("nature and nurture") contribute to a phenotype involves [[twin study|studying identical and fraternal twins]], or other siblings of [[multiple birth]]s.<ref>For example, {{cite book |title=Nature via Nurture: Genes, Experience and What Makes Us Human |vauthors=Ridley M |publisher=Fourth Estate |year=2003|isbn= 978-1-84115-745-0 |page=73}}</ref> Identical siblings are genetically the same since they come from the same zygote. Meanwhile, fraternal twins are as genetically different from one another as normal siblings. By comparing how often a certain disorder occurs in a pair of identical twins to how often it occurs in a pair of fraternal twins, scientists can determine whether that disorder is caused by genetic or postnatal environmental factors. One famous example involved the study of the [[Genain quadruplets]], who were [[Multiple birth|identical quadruplets]] all diagnosed with [[schizophrenia]].<ref name="Genain">{{Cite journal |title=The Genain Quadruplets: A Case Study and Theoretical Analysis of Heredity and Environment in Schizophrenia |journal=Behavioral Science |volume=9 |issue=4 | vauthors = Rosenthal D |year=1964 |page=371 |doi=10.1002/bs.3830090407 }}</ref>

=== Gene regulation ===
{{Main|Regulation of gene expression}}

The genome of a given organism contains thousands of genes, but not all these genes need to be active at any given moment. A gene is expressed when it is being transcribed into mRNA and there exist many cellular methods of controlling the expression of genes such that proteins are produced only when needed by the cell. [[Transcription factor]]s are regulatory proteins that bind to DNA, either promoting or inhibiting the transcription of a gene.<ref>{{cite journal | vauthors = Brivanlou AH, Darnell JE | title = Signal transduction and the control of gene expression | journal = Science | volume = 295 | issue = 5556 | pages = 813–818 | date = February 2002 | pmid = 11823631 | doi = 10.1126/science.1066355 | s2cid = 14954195 | citeseerx = 10.1.1.485.6042 | bibcode = 2002Sci...295..813B }}</ref> Within the genome of ''[[Escherichia coli]]'' bacteria, for example, there exists a series of genes necessary for the synthesis of the amino acid [[tryptophan]]. However, when tryptophan is already available to the cell, these genes for tryptophan synthesis are no longer needed. The presence of tryptophan directly affects the activity of the genes—tryptophan molecules bind to the [[Trp repressor|tryptophan repressor]] (a transcription factor), changing the repressor's structure such that the repressor binds to the genes. The tryptophan repressor blocks the transcription and expression of the genes, thereby creating [[negative feedback]] regulation of the tryptophan synthesis process.<ref>Alberts et al. (2002), [https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.section.1269#1270 II.3. Control of Gene Expression – The Tryptophan Repressor is a Simple Switch That Turns Genes On and Off in Bacteria] {{webarchive|url=https://web.archive.org/web/20070629040218/http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.section.1269 |date=29 June 2007 }}</ref>

[[File:Zinc finger DNA complex.png|thumb|upright|left|Transcription factors bind to DNA, influencing the transcription of associated genes.]]

Differences in gene expression are especially clear within [[multicellular organism]]s, where cells all contain the same genome but have very different structures and behaviors due to the expression of different sets of genes. All the cells in a multicellular organism derive from a single cell, differentiating into variant cell types in response to external and [[Cell signaling|intercellular signals]] and gradually establishing different patterns of gene expression to create different behaviors. As no single gene is responsible for the [[Ontogeny|development]] of structures within multicellular organisms, these patterns arise from the complex interactions between many cells.{{cn|date=October 2022}}

Within [[eukaryote]]s, there exist structural features of [[chromatin]] that influence the transcription of genes, often in the form of modifications to DNA and chromatin that are stably inherited by daughter cells.<ref>{{cite journal | vauthors = Jaenisch R, Bird A | title = Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals | journal = Nature Genetics | volume = 33 | issue = Suppl | pages = 245–254 | date = March 2003 | pmid = 12610534 | doi = 10.1038/ng1089 | s2cid = 17270515 }}</ref> These features are called "[[epigenetic]]" because they exist "on top" of the DNA sequence and retain inheritance from one cell generation to the next. Because of epigenetic features, different cell types [[cell culture|grown]] within the same medium can retain very different properties. Although epigenetic features are generally dynamic over the course of development, some, like the phenomenon of [[paramutation]], have multigenerational inheritance and exist as rare exceptions to the general rule of DNA as the basis for inheritance.<ref>{{cite journal | vauthors = Chandler VL | title = Paramutation: from maize to mice | journal = Cell | volume = 128 | issue = 4 | pages = 641–645 | date = February 2007 | pmid = 17320501 | doi = 10.1016/j.cell.2007.02.007 | s2cid = 6928707 | doi-access = free }}</ref>
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