Editing Genetics (section)

== Molecular basis for inheritance ==

=== DNA and chromosomes ===
{{Main|DNA|Chromosome}}

[[File:DNA chemical structure.svg|thumb|right|The [[molecular structure]] of DNA. Bases pair through the arrangement of [[hydrogen bonding]] between the strands.]]The [[Molecule|molecular]] basis for genes is [[deoxyribonucleic acid]] (DNA). DNA is composed of [[deoxyribose]] (sugar molecule), a phosphate group, and a base (amine group). There are four types of bases: [[adenine]] (A), [[cytosine]] (C), [[guanine]] (G), and [[thymine]] (T). The phosphates make phosphodiester bonds with the sugars to make long phosphate-sugar backbones. Bases specifically pair together (T&A, C&G) between two backbones and make like rungs on a ladder. The bases, phosphates, and sugars together make a [[nucleotide]] that connects to make long chains of DNA.<ref>{{Cite web | vauthors = Urry L, Cain M, Wasserman S, Minorsky P, Reece J, Campbell N |title=Campbell Biology |url=https://plus.pearson.com/courses/gregg91165/products/GTP1DPWIL20/pages/ac865b14db19976dfd6054de245cd8d8e65000756?locale=&key=2790626781132109428282022&iesCode=5VEW6xrTXI |access-date=2022-09-28 |website=plus.pearson.com}}</ref> Genetic information exists in the sequence of these nucleotides, and genes exist as stretches of sequence along the DNA chain.<ref name=Pearson_2006>{{cite journal | vauthors = Pearson H | title = Genetics: what is a gene? | journal = Nature | volume = 441 | issue = 7092 | pages = 398–401 | date = May 2006 | pmid = 16724031 | doi = 10.1038/441398a | s2cid = 4420674 | doi-access = free | bibcode = 2006Natur.441..398P }}</ref> These chains coil into a double a-helix structure and wrap around proteins called [[Histone]]s which provide the structural support. DNA wrapped around these histones are called chromosomes.<ref>{{Cite web |title=Histone |url=https://www.genome.gov/genetics-glossary/histone |access-date=2022-09-28 |website=Genome.gov |language=en}}</ref> [[Virus]]es sometimes use the similar molecule [[RNA]] instead of DNA as their genetic material.<ref>{{cite book |title=Microbiology |vauthors=Prescott LM, Harley JP, Klein DA |year=1996 |publisher=Wm. C. Brown |edition=3rd |isbn=0-697-21865-1 |url=https://archive.org/details/microbiology0000pres/page/342/mode/2up |page=343}}</ref>

DNA normally exists as a double-stranded molecule, coiled into the shape of a [[double helix]]. Each nucleotide in DNA preferentially pairs with its partner nucleotide on the opposite strand: A pairs with T, and C pairs with G. Thus, in its two-stranded form, each strand effectively contains all necessary information, redundant with its partner strand. This structure of DNA is the physical basis for inheritance: DNA replication duplicates the genetic information by splitting the strands and using each strand as a template for synthesis of a new partner strand.<ref name=griffiths2000sect1523>{{cite book | veditors = Griffiths AJ, Miller JH, Suzuki DT, Lewontin RC, Gelbart|title=An Introduction to Genetic Analysis |year=2000 |isbn=978-0-7167-3520-5 |edition=7th |publisher=W.H. Freeman |location=New York |chapter-url=https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=iga.section.1523 |chapter=Mechanism of DNA Replication}}</ref>

[[File:Human karyotype with bands and sub-bands.png|thumb|Schematic [[karyotype|karyogram]] of a human, showing 22 [[homologous chromosome]] pairs, both the female (XX) and male (XY) versions of the [[sex chromosome]] (bottom right), as well as the [[human mitochondrial genetics|mitochondrial genome]] (at bottom left) {{further|Karyotype}}]]
Genes are arranged linearly along long chains of DNA base-pair sequences. In [[bacteria]], each cell usually contains a single circular [[Nucleoid|genophore]], while [[Eukaryote|eukaryotic]] organisms (such as plants and animals) have their DNA arranged in multiple linear chromosomes. These DNA strands are often extremely long; the largest human chromosome, for example, is about 247 million [[base pair]]s in length.<ref>{{cite journal | vauthors = Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E | title = The DNA sequence and biological annotation of human chromosome 1 | journal = Nature | volume = 441 | issue = 7091 | pages = 315–321 | date = May 2006 | pmid = 16710414 | doi = 10.1038/nature04727 | doi-access = free | bibcode = 2006Natur.441..315G }}</ref> The DNA of a chromosome is associated with structural proteins that organize, compact, and control access to the DNA, forming a material called [[chromatin]]; in eukaryotes, chromatin is usually composed of [[nucleosome]]s, segments of DNA wound around cores of [[histone]] proteins.<ref>Alberts et al. (2002), [https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.section.608 II.4. DNA and chromosomes: Chromosomal DNA and Its Packaging in the Chromatin Fiber] {{webarchive|url=https://web.archive.org/web/20071018075642/http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.section.608 |date=18 October 2007 }}</ref> The full set of hereditary material in an organism (usually the combined DNA sequences of all chromosomes) is called the [[genome]].

DNA is most often found in the nucleus of cells, but Ruth Sager helped in the discovery of nonchromosomal genes found outside of the nucleus.<ref name="ruth">{{cite web |title=Ruth Sager |url=https://www.britannica.com/biography/Ruth-Sager |website=Encyclopaedia Britannica |access-date=8 June 2020}}</ref> In plants, these are often found in the chloroplasts and in other organisms, in the mitochondria.<ref name="ruth" /> These nonchromosomal genes can still be passed on by either partner in sexual reproduction and they control a variety of hereditary characteristics that replicate and remain active throughout generations.<ref name="ruth"/>

While [[haploid]] organisms have only one copy of each chromosome, most animals and many plants are [[diploid]], containing two of each chromosome and thus two copies of every gene. The two alleles for a gene are located on identical [[Locus (genetics)|loci]] of the two [[homologous chromosomes]], each allele inherited from a different parent.<ref name=griffiths2000sect484>{{cite book | veditors = Griffiths AJ, Miller JH, Suzuki DT, Lewontin RC, Gelbart|title=An Introduction to Genetic Analysis |year=2000 |isbn=978-0-7167-3520-5 |edition=7th |publisher=W.H. Freeman |location=New York |chapter-url=https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=iga.section.484 |chapter=Mendelian genetics in eukaryotic life cycles}}</ref>

Many species have so-called [[sex chromosome]]s that determine the sex of each organism.<ref name="griffiths2000sect222">{{cite book | veditors = Griffiths AJ, Miller JH, Suzuki DT, Lewontin RC, Gelbart|title=An Introduction to Genetic Analysis |year=2000 |isbn=978-0-7167-3520-5 |edition=7th |publisher=W.H. Freeman |location=New York |chapter-url=https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=iga.section.222 |chapter=Sex chromosomes and sex-linked inheritance}}</ref> In humans and many other animals, the [[Y chromosome]] contains the gene that triggers the development of the specifically male characteristics. In evolution, this chromosome has lost most of its content and also most of its genes, while the [[X chromosome]] is similar to the other chromosomes and contains many genes. This being said, Mary Frances Lyon discovered that there is X-chromosome inactivation during reproduction to avoid passing on twice as many genes to the offspring.<ref name="lyon">{{cite journal | vauthors = Rastan S | title = Mary F. Lyon (1925-2014) | journal = Nature | volume = 518 | issue = 7537 | pages = 36 | date = February 2015 | pmid = 25652989 | doi = 10.1038/518036a | publisher = Springer Nature Limited | s2cid = 4405984 | bibcode = 2015Natur.518...36R | doi-access = free }}</ref> Lyon's discovery led to the discovery of X-linked diseases.<ref name="lyon" />

=== Reproduction ===
{{Main|Asexual reproduction|Sexual reproduction}}

[[File:Zellsubstanz-Kern-Kerntheilung.jpg|thumb|left|[[Walther Flemming]]'s 1882 diagram of eukaryotic cell division. Chromosomes are copied, condensed, and organized. Then, as the cell divides, chromosome copies separate into the daughter cells.]]

When cells divide, their full genome is copied and each [[Cell division|daughter cell]] inherits one copy. This process, called [[mitosis]], is the simplest form of reproduction and is the basis for asexual reproduction. Asexual reproduction can also occur in multicellular organisms, producing offspring that inherit their genome from a single parent. Offspring that are genetically identical to their parents are called [[Cloning|clones]].<ref>{{cite web |url=https://www.merriam-webster.com/dictionary/clone |title= clone|author=<!--Not stated--> |date= |website=Merriam-Webster Dictionary |publisher= |access-date=13 November 2023 |quote=}}</ref>

[[Eukaryote|Eukaryotic]] organisms often use sexual reproduction to generate offspring that contain a mixture of genetic material inherited from two different parents. The process of sexual reproduction alternates between forms that contain single copies of the genome ([[haploid]]) and double copies ([[diploid]]).<ref name=griffiths2000sect484 /> Haploid cells fuse and combine genetic material to create a diploid cell with paired chromosomes. Diploid organisms form haploids by dividing, without replicating their DNA, to create daughter cells that randomly inherit one of each pair of chromosomes. Most animals and many plants are diploid for most of their lifespan, with the haploid form reduced to single cell [[gamete]]s such as [[sperm]] or [[Ovum|eggs]].<ref>{{Cite web |title=Haploid |url=https://www.genome.gov/genetics-glossary/haploid |access-date=2024-02-10 |website=www.genome.gov |language=en}}</ref>

Although they do not use the haploid/diploid method of sexual reproduction, [[bacteria]] have many methods of acquiring new genetic information. Some bacteria can undergo [[Bacterial conjugation|conjugation]], transferring a small circular piece of DNA to another bacterium.<ref name="griffiths2000sect1304">{{cite book | veditors = Griffiths AJ, Miller JH, Suzuki DT, Lewontin RC, Gelbart|title=An Introduction to Genetic Analysis |year=2000 |isbn=978-0-7167-3520-5 |edition=7th |publisher=W.H. Freeman |location=New York |chapter-url=https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=iga.section.1304 |chapter=Bacterial conjugation}}</ref> Bacteria can also take up raw DNA fragments found in the environment and integrate them into their genomes, a phenomenon known as [[Transformation (genetics)|transformation]].<ref name="griffiths2000sect1343">{{cite book | veditors = Griffiths AJ, Miller JH, Suzuki DT, Lewontin RC, Gelbart|title=An Introduction to Genetic Analysis |year=2000 |isbn=978-0-7167-3520-5 |edition=7th |publisher=W.H. Freeman |location=New York |chapter-url=https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=iga.section.1343 |chapter=Bacterial transformation}}</ref> These processes result in [[horizontal gene transfer]], transmitting fragments of genetic information between organisms that would be otherwise unrelated. [[Transformation (genetics)|Natural bacterial transformation]] occurs in many [[bacteria]]l species, and can be regarded as a [[sexual reproduction|sexual process]] for transferring DNA from one cell to another cell (usually of the same species).<ref name=Bernstein2018>{{cite journal | vauthors = Bernstein H, Bernstein C, Michod RE | title = Sex in microbial pathogens | journal = Infection, Genetics and Evolution | volume = 57 | pages = 8–25 | date = January 2018 | pmid = 29111273 | doi = 10.1016/j.meegid.2017.10.024 | doi-access = free | bibcode = 2018InfGE..57....8B }}</ref> Transformation requires the action of numerous bacterial [[gene product]]s, and its primary adaptive function appears to be [[DNA repair|repair]] of [[DNA damage (naturally occurring)|DNA damages]] in the recipient cell.<ref name=Bernstein2018 />

=== Recombination and genetic linkage ===
{{Main|Chromosomal crossover|Genetic linkage}}

[[File:Morgan crossover 2 cropped.png|thumb|right|[[Thomas Hunt Morgan]]'s 1916 illustration of a double crossover between chromosomes]]

The diploid nature of chromosomes allows for genes on different chromosomes to [[independent assortment|assort independently]] or be separated from their homologous pair during sexual reproduction wherein haploid gametes are formed. In this way new combinations of genes can occur in the offspring of a mating pair. Genes on the same chromosome would theoretically never recombine. However, they do, via the cellular process of [[chromosomal crossover]]. During crossover, chromosomes exchange stretches of DNA, effectively shuffling the gene alleles between the chromosomes.<ref name="griffiths2000sect929">{{cite book | veditors = Griffiths AJ, Miller JH, Suzuki DT, Lewontin RC, Gelbar |title=An Introduction to Genetic Analysis |year=2000 |isbn=978-0-7167-3520-5 |edition=7th |publisher=W. H. Freeman |location=New York |chapter-url=https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=iga.section.929 |chapter=Nature of crossing-over}}</ref> This process of chromosomal crossover generally occurs during [[meiosis]], a series of cell divisions that creates haploid cells. [[Origin and function of meiosis|Meiotic recombination]], particularly in microbial [[eukaryote]]s, appears to serve the adaptive function of repair of DNA damages.<ref name=Bernstein2018/>

The first cytological demonstration of crossing over was performed by Harriet Creighton and [[Barbara McClintock]] in 1931. Their research and experiments on corn provided cytological evidence for the genetic theory that linked genes on paired chromosomes do in fact exchange places from one homolog to the other.<ref>{{cite journal | vauthors = Creighton HB, McClintock B | title = A Correlation of Cytological and Genetical Crossing-Over in Zea Mays | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 17 | issue = 8 | pages = 492–497 | date = August 1931 | pmid = 16587654 | pmc = 1076098 | doi = 10.1073/pnas.17.8.492 | doi-access = free | bibcode = 1931PNAS...17..492C }}</ref>

The probability of chromosomal crossover occurring between two given points on the chromosome is related to the distance between the points. For an arbitrarily long distance, the probability of crossover is high enough that the inheritance of the genes is effectively uncorrelated.<ref name="Staub1994">{{cite book | vauthors = Staub JE |title=Crossover: Concepts and Applications in Genetics, Evolution, and Breeding |url=https://books.google.com/books?id=R43qWg5A-GsC&pg=PA55 |year=1994 |publisher=University of Wisconsin Press |isbn=978-0-299-13564-5 |page=55}}</ref> For genes that are closer together, however, the lower probability of crossover means that the genes demonstrate genetic linkage; alleles for the two genes tend to be inherited together. The amounts of linkage between a series of genes can be combined to form a linear [[Genetic linkage#Linkage map|linkage map]] that roughly describes the arrangement of the genes along the chromosome.<ref name="griffiths2000sect899">{{cite book | veditors = Griffiths AJ, Miller JH, Suzuki DT, Lewontin RC, Gelbar |title=An Introduction to Genetic Analysis |year=2000 |isbn=978-0-7167-3520-5 |edition=7th |publisher=W. H. Freeman |location=New York |chapter-url=https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=iga.section.899 |chapter=Linkage maps}}</ref>