Genetics is the study ofgenes,genetic variation, andheredity inorganisms.[1][2][3] It is an important branch inbiology because heredity is vital to organisms'evolution.Gregor Mendel, aMoravianAugustinian friar working in the 19th century inBrno, was the first to study genetics scientifically. Mendel studied "trait inheritance", patterns in the way traits are handed down from parents to offspring over time. He observed that organisms (pea plants) inherit traits by way of discrete "units of inheritance". This term, still used today, is a somewhat ambiguous definition of what is referred to as a gene.
Trait inheritance andmolecular inheritance mechanisms of genes are still primary principles of genetics in the 21st century, but modern genetics has expanded to study the function and behavior of genes. Gene structure and function, variation, and distribution are studied within the context of thecell, the organism (e.g.dominance), and within the context of a population. Genetics has given rise to a number of subfields, includingmolecular genetics,epigenetics,population genetics, andpaleogenetics. Organisms studied within the broad field span the domains of life (archaea,bacteria, andeukarya).
Genetic processes work in combination with an organism's environment and experiences to influence development andbehavior, often referred to asnature versus nurture. Theintracellular orextracellular environment of a living cell or organism may increase or decrease gene transcription. A classic example is two seeds of genetically identical corn, one placed in atemperate climate and one in anarid climate (lacking sufficient waterfall or rain). While the average height the two corn stalks could grow to is genetically determined, the one in the arid climate only grows to half the height of the one in the temperate climate due to lack of water and nutrients in its environment.
The wordgenetics stems from theancient Greekγενετικόςgenetikos meaning "genitive"/"generative", which in turn derives fromγένεσιςgenesis meaning "origin".[4][5][6]
The observation that living things inherittraits from their parents has been used since prehistoric times to improve crop plants and animals throughselective breeding.[7][8] The modern science of genetics, seeking to understand this process, began with the work of theAugustinian friarGregor Mendel in the mid-19th century.[9]
Prior to Mendel,Imre Festetics, aHungarian noble, who lived in Kőszeg before Mendel, was the first who used the word "genetic" in hereditarian context, and is considered the first geneticist. He described several rules of biological inheritance in his workThe genetic laws of nature (Die genetischen Gesetze der Natur, 1819).[10] His second law is the same as that which Mendel published.[11] In his third law, he developed the basic principles of mutation (he can be considered a forerunner ofHugo de Vries).[12] Festetics argued that changes observed in the generation of farm animals, plants, and humans are the result of scientific laws.[13] Festetics empirically deduced that organisms inherit their characteristics, not acquire them. He recognized recessive traits and inherent variation by postulating that traits of past generations could reappear later, and organisms could produce progeny with different attributes.[14] These observations represent an important prelude to Mendel's theory of particulate inheritance insofar as it features a transition of heredity from its status as myth to that of a scientific discipline, by providing a fundamental theoretical basis for genetics in the twentieth century.[10][15]
Other theories of inheritance preceded Mendel's work. A popular theory during the 19th century, and implied byCharles Darwin's 1859On the Origin of Species, wasblending inheritance: the idea that individuals inherit a smooth blend of traits from their parents.[16] Mendel's work provided examples where traits were definitely not blended after hybridization, showing that traits are produced by combinations of distinct genes rather than a continuous blend. Blending of traits in the progeny is now explained by the action of multiple genes withquantitative effects. Another theory that had some support at that time was theinheritance of acquired characteristics: the belief that individuals inherit traits strengthened by their parents. This theory (commonly associated withJean-Baptiste Lamarck) is now known to be wrong—the experiences of individuals do not affect the genes they pass to their children.[17] Other theories included Darwin'spangenesis (which had both acquired and inherited aspects) andFrancis Galton's reformulation of pangenesis as both particulate and inherited.[18]
Morgan's observation ofsex-linked inheritance of a mutation causing white eyes inDrosophila led him to the hypothesis that genes are located upon chromosomes.
Modern genetics started with Mendel's studies of the nature of inheritance in plants. In his paper "Versuche über Pflanzenhybriden" ("Experiments on Plant Hybridization"), presented in 1865 to theNaturforschender Verein (Society for Research in Nature) inBrno, Mendel traced the inheritance patterns of certain traits in pea plants and described them mathematically. Although this pattern of inheritance could only be observed for a few traits, Mendel's work suggested that heredity was particulate, not acquired, and that the inheritance patterns of many traits could be explained through simple rules and ratios.[19]
The importance of Mendel's work did not gain wide understanding until 1900, after his death, whenHugo de Vries and other scientists rediscovered his research.William Bateson, a proponent of Mendel's work, coined the wordgenetics in 1905.[20][21] The adjectivegenetic, derived from the Greek wordgenesis—γένεσις, "origin", predates the noun and was first used in a biological sense in 1860.[22] Bateson both acted as a mentor and was aided significantly by the work of other scientists from Newnham College at Cambridge, specifically the work ofBecky Saunders,Nora Darwin Barlow, andMuriel Wheldale Onslow.[23] Bateson popularized the usage of the wordgenetics to describe the study of inheritance in his inaugural address to the Third International Conference on Plant Hybridization inLondon in 1906.[24]
After the rediscovery of Mendel's work, scientists tried to determine which molecules in the cell were responsible for inheritance. In 1900, Nettie Stevens began studying the mealworm.[25] Over the next 11 years, she discovered that females only had the X chromosome and males had both X and Y chromosomes.[25] She was able to conclude that sex is a chromosomal factor and is determined by the male.[25] In 1911,Thomas Hunt Morgan argued that genes are onchromosomes, based on observations of a sex-linkedwhite eye mutation infruit flies.[26] In 1913, his studentAlfred Sturtevant used the phenomenon ofgenetic linkage to show that genes are arranged linearly on the chromosome.[27]
DNA, the molecular basis forbiological inheritance. Each strand of DNA is a chain ofnucleotides, matching each other in the center to form what look like rungs on a twisted ladder.
Although genes were known to exist on chromosomes, chromosomes are composed of bothprotein andDNA, and scientists did not know which of the two is responsible for inheritance.In 1928,Frederick Griffith discovered the phenomenon oftransformation: dead bacteria could transfergenetic material to "transform" other still-living bacteria. Sixteen years later, in 1944, theAvery–MacLeod–McCarty experiment identified DNA as the molecule responsible for transformation.[28] The role of the nucleus as the repository of genetic information in eukaryotes had been established byHämmerling in 1943 in his work on the single celled algaAcetabularia.[29] TheHershey–Chase experiment in 1952 confirmed that DNA (rather than protein) is the genetic material of the viruses that infect bacteria, providing further evidence that DNA is the molecule responsible for inheritance.[30]
James Watson andFrancis Crick determined the structure of DNA in 1953, using theX-ray crystallography work ofRosalind Franklin andMaurice Wilkins that indicated DNA has ahelical structure (i.e., shaped like a corkscrew).[31][32] Their double-helix model had two strands of DNA with the nucleotides pointing inward, each matching a complementary nucleotide on the other strand to form what look like rungs on a twisted ladder.[33] This structure showed that genetic information exists in the sequence of nucleotides on each strand of DNA. The structure also suggested a simple method forreplication: if the strands are separated, new partner strands can be reconstructed for each based on the sequence of the old strand. This property is what gives DNA its semi-conservative nature where one strand of new DNA is from an original parent strand.[34]
Although the structure of DNA showed how inheritance works, it was still not known how DNA influences the behavior of cells. In the following years, scientists tried to understand how DNA controls the process ofprotein production.[35] It was discovered that the cell uses DNA as a template to create matchingmessenger RNA, molecules withnucleotides very similar to DNA. The nucleotide sequence of a messenger RNA is used to create anamino acid sequence in protein; this translation between nucleotide sequences and amino acid sequences is known as thegenetic code.[36]
APunnett square depicting a cross between two pea plants heterozygous for purple (B) and white (b) blossoms
At its most fundamental level, inheritance in organisms occurs by passing discrete heritable units, calledgenes, from parents to offspring.[43] This property was first observed by Gregor Mendel, who studied the segregation of heritable traits inpea plants, showing for example that flowers on a single plant were either purple or white—but never an intermediate between the two colors. The discrete versions of the same gene controlling the inherited appearance (phenotypes) are calledalleles.[19][44]
In the case of the pea, which is adiploid species, each individual plant has two copies of each gene, one copy inherited from each parent.[45] Many species, including humans, have this pattern of inheritance. Diploid organisms with two copies of the same allele of a given gene are calledhomozygous at thatgene locus, while organisms with two different alleles of a given gene are calledheterozygous. The set of alleles for a given organism is called itsgenotype, while the observable traits of the organism are called itsphenotype. When organisms are heterozygous at a gene, often one allele is calleddominant as its qualities dominate the phenotype of the organism, while the other allele is calledrecessive as its qualities recede and are not observed. Some alleles do not have complete dominance and instead haveincomplete dominance by expressing an intermediate phenotype, orcodominance by expressing both alleles at once.[46]
When a pair of organismsreproduce sexually, their offspring randomly inherit one of the two alleles from each parent. These observations of discrete inheritance and the segregation of alleles are collectively known asMendel's first law or the Law of Segregation. However, the probability of getting one gene over the other can change due to dominant, recessive, homozygous, or heterozygous genes. For example, Mendel found that if you cross heterozygous organisms your odds of getting the dominant trait is 3:1. Real geneticist study and calculate probabilities by using theoretical probabilities, empirical probabilities, the product rule, the sum rule, and more.[47]
Genetic pedigree charts help track the inheritance patterns of traits.
Geneticists use diagrams and symbols to describe inheritance. A gene is represented by one or a few letters. Often a "+" symbol is used to mark the usual,non-mutant allele for a gene.[48]
In fertilization and breeding experiments (and especially when discussing Mendel's laws) the parents are referred to as the "P" generation and the offspring as the "F1" (first filial) generation. When the F1 offspring mate with each other, the offspring are called the "F2" (second filial) generation. One of the common diagrams used to predict the result of cross-breeding is thePunnett square.[49]
When studying human genetic diseases, geneticists often usepedigree charts to represent the inheritance of traits.[50] These charts map the inheritance of a trait in a family tree.
Human height is a trait with complex genetic causes.Francis Galton's data from 1889 shows the relationship between offspring height as a function of mean parent height.
Organisms have thousands of genes, and in sexually reproducing organisms these genes generally assort independently of each other. This means that the inheritance of an allele for yellow or green pea color is unrelated to the inheritance of alleles for white or purple flowers. This phenomenon, known as "Mendel's second law[broken anchor]" or the "law of independent assortment," means that the alleles of different genes get shuffled between parents to form offspring with many different combinations. Different genes often interact to influence the same trait. In theBlue-eyed Mary (Omphalodes verna), for example, there exists a gene with alleles that determine the color of flowers: blue or magenta. Another gene, however, controls whether the flowers have color at all or are white. When a plant has two copies of this white allele, its flowers are white—regardless of whether the first gene has blue or magenta alleles. This interaction between genes is calledepistasis, with the second gene epistatic to the first.[51]
Many traits are not discrete features (e.g. purple or white flowers) but are instead continuous features (e.g. human height andskin color). Thesecomplex traits are products of many genes.[52] The influence of these genes is mediated, to varying degrees, by the environment an organism has experienced. The degree to which an organism's genes contribute to a complex trait is calledheritability.[53] Measurement of the heritability of a trait is relative—in a more variable environment, the environment has a bigger influence on the total variation of the trait. For example, human height is a trait with complex causes. It has a heritability of 89% in the United States. In Nigeria, however, where people experience a more variable access to good nutrition andhealth care, height has a heritability of only 62%.[54]
Themolecular basis for genes isdeoxyribonucleic acid (DNA). DNA is composed ofdeoxyribose (sugar molecule), a phosphate group, and a base (amine group). There are four types of bases:adenine (A),cytosine (C),guanine (G), andthymine (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 anucleotide that connects to make long chains of DNA.[55] Genetic information exists in the sequence of these nucleotides, and genes exist as stretches of sequence along the DNA chain.[56] These chains coil into a double a-helix structure and wrap around proteins calledHistones which provide the structural support. DNA wrapped around these histones are called chromosomes.[57]Viruses sometimes use the similar moleculeRNA instead of DNA as their genetic material.[58]
DNA normally exists as a double-stranded molecule, coiled into the shape of adouble 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.[59]
Genes are arranged linearly along long chains of DNA base-pair sequences. Inbacteria, each cell usually contains a single circulargenophore, whileeukaryotic 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 millionbase pairs in length.[60] The DNA of achromosome is associated with structural proteins that organize, compact, and control access to the DNA, forming a material calledchromatin; in eukaryotes, chromatin is usually composed ofnucleosomes, segments of DNA wound around cores ofhistone proteins.[61] The full set of hereditary material in an organism (usually the combined DNA sequences of all chromosomes) is called thegenome.
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.[62] In plants, these are often found in the chloroplasts and in other organisms, in the mitochondria.[62] 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.[62]
Whilehaploid organisms have only one copy of each chromosome, most animals and many plants arediploid, containing two of each chromosome and thus two copies of every gene. The two alleles for a gene are located on identicalloci of the twohomologous chromosomes, each allele inherited from a different parent.[45]
Many species have so-calledsex chromosomes that determine the sex of each organism.[63] In humans and many other animals, theY 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 theX 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.[64] Lyon's discovery led to the discovery of X-linked diseases.[64]
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 eachdaughter cell inherits one copy. This process, calledmitosis, 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 calledclones.[65]
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).[45] 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 cellgametes such assperm oreggs.[66]
Although they do not use the haploid/diploid method of sexual reproduction,bacteria have many methods of acquiring new genetic information. Some bacteria can undergoconjugation, transferring a small circular piece of DNA to another bacterium.[67] Bacteria can also take up raw DNA fragments found in the environment and integrate them into their genomes, a phenomenon known astransformation.[68] These processes result inhorizontal gene transfer, transmitting fragments of genetic information between organisms that would be otherwise unrelated.Natural bacterial transformation occurs in manybacterial species, and can be regarded as asexual process for transferring DNA from one cell to another cell (usually of the same species).[69] Transformation requires the action of numerous bacterialgene products, and its primary adaptive function appears to berepair ofDNA damages in the recipient cell.[69]
Thomas Hunt Morgan's 1916 illustration of a double crossover between chromosomes
The diploid nature of chromosomes allows for genes on different chromosomes toassort 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 ofchromosomal crossover. During crossover, chromosomes exchange stretches of DNA, effectively shuffling the gene alleles between the chromosomes.[70] This process of chromosomal crossover generally occurs duringmeiosis, a series of cell divisions that creates haploid cells.Meiotic recombination, particularly in microbialeukaryotes, appears to serve the adaptive function of repair of DNA damages.[69]
The first cytological demonstration of crossing over was performed by Harriet Creighton andBarbara 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.[71]
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.[72] 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 linearlinkage map that roughly describes the arrangement of the genes along the chromosome.[73]
Genesexpress 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 ofamino acids. The DNA sequence of a gene is used to produce a specificamino acid sequence. This process begins with the production of an RNA molecule with a sequence matching the gene's DNA sequence, a process calledtranscription.
Thismessenger RNA molecule then serves to produce a corresponding amino acid sequence through a process calledtranslation. Each group of three nucleotides in the sequence, called acodon, corresponds either to one of the twenty possible amino acids in a protein or aninstruction to end the amino acid sequence; this correspondence is called thegenetic code.[74] 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 phenomenonFrancis Crick called thecentral dogma of molecular biology.[75]
The specific sequence of amino acidsresults in a unique three-dimensional structure for that protein, and the three-dimensional structures of proteins are related to their functions.[76][77] Some are simple structural molecules, like the fibers formed by the proteincollagen. Proteins can bind to other proteins and simple molecules, sometimes acting asenzymes by facilitatingchemical reactions within the bound molecules (without changing the structure of the protein itself). Protein structure is dynamic; the proteinhemoglobin bends into slightly different forms as it facilitates the capture, transport, and release of oxygen molecules within mammalian blood.[78]
Asingle 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 humangenetic disease that results from a single base difference within thecoding region for the β-globin section of hemoglobin, causing a single amino acid change that changes hemoglobin's physical properties.[79]Sickle-cell versions of hemoglobin stick to themselves, stacking to form fibers that distort the shape ofred blood cells carrying the protein. These sickle-shaped cells no longer flow smoothly throughblood vessels, having a tendency to clog or degrade, causing the medical problems associated with this disease.[80]
Some DNA sequences are transcribed into RNA but are not translated into protein products—such RNA molecules are callednon-coding RNA. In some cases, these products fold into structures which are involved in critical cell functions (e.g.ribosomal RNA andtransfer RNA). RNA can also have regulatory effects through hybridization interactions with other RNA molecules (such asmicroRNA).[81]
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 theSiamese 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) anddenature 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—so the cat has dark hair at its extremities.[82]
Environment plays a major role in effects of the human genetic diseasephenylketonuria. The mutation that causes phenylketonuria disrupts the ability of the body to break down the amino acidphenylalanine, 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.[83]
A common method for determining how genes and environment ("nature and nurture") contribute to a phenotype involvesstudying identical and fraternal twins, or other siblings ofmultiple births.[84] 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 theGenain quadruplets, who wereidentical quadruplets all diagnosed withschizophrenia.[85]
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 factors are regulatory proteins that bind to DNA, either promoting or inhibiting the transcription of a gene.[86] Within the genome ofEscherichia coli bacteria, for example, there exists a series of genes necessary for the synthesis of the amino acidtryptophan. 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 thetryptophan 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 creatingnegative feedback regulation of the tryptophan synthesis process.[87]
Transcription factors bind to DNA, influencing the transcription of associated genes.
Differences in gene expression are especially clear withinmulticellular organisms, 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 andintercellular signals and gradually establishing different patterns of gene expression to create different behaviors.
Withineukaryotes, there exist structural features ofchromatin that influence the transcription of genes, often in the form of modifications to DNA and chromatin that are stably inherited by daughter cells.[88] 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 typesgrown within the same medium can retain very different properties. Although epigenetic features are generally dynamic over the course of development, some, like the phenomenon ofparamutation, have multigenerational inheritance and exist as rare exceptions to the general rule of DNA as the basis for inheritance.[89]
Gene duplication allows diversification by providing redundancy: one gene can mutate and lose its original function without harming the organism.
During the process of DNA replication, errors occasionally occur in the polymerization of the second strand. These errors, called mutations, can affect the phenotype of an organism, especially if they occur within the protein coding sequence of a gene. Error rates are usually very low—1 error in every 10–100 million bases—due to the "proofreading" ability ofDNA polymerases.[90][91] Processes that increase the rate of changes in DNA are calledmutagenic: mutagenic chemicals promote errors in DNA replication, often by interfering with the structure of base-pairing, whileUV radiation induces mutations by causing damage to the DNA structure.[92] Chemical damage to DNA occurs naturally as well and cells useDNA repair mechanisms to repair mismatches and breaks. The repair does not, however, always restore the original sequence. A particularly important source of DNA damages appears to bereactive oxygen species[93] produced bycellular aerobic respiration, and these can lead to mutations.[94]
In organisms that usechromosomal crossover to exchange DNA and recombine genes, errors in alignment during meiosis can also cause mutations. Errors in crossover are especially likely when similar sequences cause partner chromosomes to adopt a mistaken alignment; this makes some regions in genomes more prone to mutating in this way. These errors create large structural changes in DNA sequence—duplications,inversions,deletions of entire regions—or the accidental exchange of whole parts of sequences between different chromosomes,chromosomal translocation.[95]
This is a diagram showing mutations in an RNA sequence. Figure (1) is a normal RNA sequence, consisting of 4 codons. Figure (2) shows a missense, single point, non silent mutation. Figures (3 and 4) both showframeshift mutations, which is why they are grouped together. Figure 3 shows a deletion of the second base pair in the second codon. Figure 4 shows an insertion in the third base pair of the second codon. Figure (5) shows a repeat expansion, where an entire codon is duplicated.
Mutations alter an organism's genotype and occasionally this causes different phenotypes to appear. Most mutations have little effect on an organism's phenotype, health, or reproductivefitness.[96] Mutations that do have an effect are usually detrimental, but occasionally some can be beneficial.[97] Studies in the flyDrosophila melanogaster suggest that if a mutation changes a protein produced by a gene, about 70 percent of these mutations are harmful with the remainder being either neutral or weakly beneficial.[98]
Over many generations, the genomes of organisms can change significantly, resulting in evolution. In the process calledadaptation, selection for beneficial mutations can cause a species to evolve into forms better able to survive in their environment.[103] New species are formed through the process ofspeciation, often caused by geographical separations that prevent populations from exchanging genes with each other.[104]
By comparing thehomology between different species' genomes, it is possible to calculate the evolutionary distance between them andwhen they may have diverged. Genetic comparisons are generally considered a more accurate method of characterizing the relatedness between species than the comparison of phenotypic characteristics. The evolutionary distances between species can be used to formevolutionary trees; these trees represent thecommon descent and divergence of species over time, although they do not show the transfer of genetic material between unrelated species (known ashorizontal gene transfer and most common in bacteria).[105]
Although geneticists originally studied inheritance in a wide variety of organisms, the range of species studied has narrowed. One reason is that when significant research already exists for a given organism, new researchers are more likely to choose it for further study, and so eventually a fewmodel organisms became the basis for most genetics research. Common research topics in model organism genetics include the study ofgene regulation and the involvement of genes indevelopment andcancer. Organisms were chosen, in part, for convenience—short generation times and easygenetic manipulation made some organisms popular genetics research tools. Widely used model organisms include the gut bacteriumEscherichia coli, the plantArabidopsis thaliana, baker's yeast (Saccharomyces cerevisiae), the nematodeCaenorhabditis elegans, the common fruit fly (Drosophila melanogaster), the zebrafish (Danio rerio), and the common house mouse (Mus musculus).[106]
Medical genetics seeks to understand how genetic variation relates to human health and disease.[107] When searching for an unknown gene that may be involved in a disease, researchers commonly use genetic linkage and geneticpedigree charts to find the location on the genome associated with the disease. At the population level, researchers take advantage of genome wide association studies (GWAS) to look for locations in the genome that are associated with diseases, a method especially useful formultigenic traits not clearly defined by a single gene.[108] Once a candidate gene is found, further research is often done on the corresponding (orhomologous) genes of modelorganisms. In addition to studying genetic diseases, the increased availability of genotyping methods has led to the field ofpharmacogenetics: the study of how genotype can affect drug responses.[109]
Individuals differ in their inherited tendency to developcancer, and cancer is a genetic disease. The process of cancer development in the body is a combination of events. Mutations occasionally occur within cells in the body as they divide. Although these mutations will not be inherited by any offspring, they can affect the behavior of cells, sometimes causing them to grow and divide more frequently. There are biological mechanisms that attempt to stop this process; signals are given to inappropriately dividing cells that should triggercell death, but sometimes additional mutations occur that cause cells to ignore these messages. An internal process ofnatural selection occurs within the body and eventually mutations accumulate within cells to promote their own growth, creating a canceroustumor that grows and invades various tissues of the body. Normally, a cell divides only in response to signals calledgrowth factors andstops growing once in contact with surrounding cells and in response to growth-inhibitory signals. It usually then divides a limited number of times and dies, staying within theepithelium where it is unable to migrate to other organs. To become a cancer cell, a cell has to accumulate mutations in a number of genes (three to seven). A cancer cell can divide without growth factor and ignores inhibitory signals. Also, it is immortal and can grow indefinitely, even after it makes contact with neighboring cells. It may escape from the epithelium and ultimately from theprimary tumor. Then, the escaped cell can cross the endothelium of a blood vessel and get transported by the bloodstream to colonize a new organ, forming deadlymetastasis. Although there are some genetic predispositions in a small fraction of cancers, the major fraction is due to a set of new genetic mutations that originally appear and accumulate in one or a small number of cells that will divide to form the tumor and are not transmitted to the progeny (somatic mutations). The most frequent mutations are a loss of function ofp53 protein, atumor suppressor, or in the p53 pathway, and gain of function mutations in theRas proteins, or in otheroncogenes.[110][111]
DNA can be manipulated in the laboratory.Restriction enzymes are commonly used enzymes that cut DNA at specific sequences, producing predictable fragments of DNA.[112] DNA fragments can be visualized through use ofgel electrophoresis, which separates fragments according to their length.[113]
The use ofligation enzymes allows DNA fragments to be connected. By binding ("ligating") fragments of DNA together from different sources, researchers can createrecombinant DNA, the DNA often associated withgenetically modified organisms. Recombinant DNA is commonly used in the context ofplasmids: short circular DNA molecules with a few genes on them. In the process known asmolecular cloning, researchers can amplify the DNA fragments by inserting plasmids into bacteria and then culturing them on plates of agar (to isolateclones of bacteria cells). "Cloning" can also refer to the various means of creating cloned ("clonal") organisms.[114]
DNA can also be amplified using a procedure called thepolymerase chain reaction (PCR).[115] By using specific short sequences of DNA, PCR can isolate and exponentially amplify a targeted region of DNA. Because it can amplify from extremely small amounts of DNA, PCR is also often used to detect the presence of specific DNA sequences.[116][117]
DNA sequencing, one of the most fundamental technologies developed to study genetics, allows researchers to determine the sequence of nucleotides in DNA fragments. The technique ofchain-termination sequencing, developed in 1977 by a team led byFrederick Sanger, is still routinely used to sequence DNA fragments. Using this technology, researchers have been able to study the molecular sequences associated with many human diseases.[118]
As sequencing has become less expensive, researchers havesequenced the genomes of many organisms using a process calledgenome assembly, which uses computational tools to stitch together sequences from many different fragments.[119] These technologies were used to sequence the human genome in the Human Genome Project completed in 2003.[41] Newhigh-throughput sequencing technologies are dramatically lowering the cost of DNA sequencing, with many researchers hoping to bring the cost of resequencing a human genome down to a thousand dollars.[120]
Next-generation sequencing (or high-throughput sequencing) came about due to the ever-increasing demand for low-cost sequencing. These sequencing technologies allow the production of potentially millions of sequences concurrently.[121][122] The large amount of sequence data available has created the subfield ofgenomics, research that uses computational tools to search for and analyze patterns in the full genomes of organisms. Genomics can also be considered a subfield ofbioinformatics, which uses computational approaches to analyze large sets ofbiological data.
On 19 March 2015, a group of leading biologists urged a worldwide ban on clinical use of methods, particularly the use ofCRISPR andzinc finger, to edit the human genome in a way that can be inherited.[123][124][125][126] In April 2015, Chinese researchersreported results ofbasic research to edit the DNA of non-viablehuman embryos using CRISPR.[127][128]
^"Genetikos (γενετ-ικός)".Henry George Liddell, Robert Scott, A Greek-English Lexicon. Perseus Digital Library, Tufts University.Archived from the original on 15 June 2010. Retrieved20 February 2012.
^"Genesis (γένεσις)".Henry George Liddell, Robert Scott, A Greek-English Lexicon. Perseus Digital Library, Tufts University.Archived from the original on 15 June 2010. Retrieved20 February 2012.
^"Genetic".Online Etymology Dictionary.Archived from the original on 23 August 2011. Retrieved20 February 2012.
^Weiling F (July 1991). "Historical study: Johann Gregor Mendel 1822-1884".American Journal of Medical Genetics.40 (1):1–25, discussion 26.doi:10.1002/ajmg.1320400103.PMID1887835.
^Peter J. Bowler,The Mendelian Revolution: The Emergency of Hereditarian Concepts in Modern Science and Society (Baltimore: Johns Hopkins University Press, 1989): chapters 2 & 3.
^Bateson W (1907). "The Progress of Genetic Research". In Wilks, W (ed.).Report of the Third 1906 International Conference on Genetics: Hybridization (the cross-breeding of genera or species), the cross-breeding of varieties, and general plant breeding. London: Royal Horticultural Society. :Initially titled the "International Conference on Hybridisation and Plant Breeding", the title was changed as a result of Bateson's speech. See:Cock AG, Forsdyke DR (2008).Treasure your exceptions: the science and life of William Bateson. Springer. p. 248.ISBN978-0-387-75687-5.
^Judson H (1979).The Eighth Day of Creation: Makers of the Revolution in Biology. Cold Spring Harbor Laboratory Press. pp. 51–169.ISBN978-0-87969-477-7.
^Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA, et al. (December 1985). "Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia".Science.230 (4732):1350–1354.Bibcode:1985Sci...230.1350S.doi:10.1126/science.2999980.PMID2999980.
^Griffiths AJ, Miller JH, Suzuki DT, Lewontin RC, Gelbar, eds. (2000)."Nature of crossing-over".An Introduction to Genetic Analysis (7th ed.). New York: W. H. Freeman.ISBN978-0-7167-3520-5.
^Griffiths AJ, Miller JH, Suzuki DT, Lewontin RC, Gelbar, eds. (2000)."Linkage maps".An Introduction to Genetic Analysis (7th ed.). New York: W. H. Freeman.ISBN978-0-7167-3520-5.
^"How Does Sickle Cell Cause Disease?". Brigham and Women's Hospital: Information Center for Sickle Cell and Thalassemic Disorders. 11 April 2002.Archived from the original on 23 September 2010. Retrieved23 July 2007.
^For example,Ridley M (2003).Nature via Nurture: Genes, Experience and What Makes Us Human. Fourth Estate. p. 73.ISBN978-1-84115-745-0.
^Rosenthal D (1964). "The Genain Quadruplets: A Case Study and Theoretical Analysis of Heredity and Environment in Schizophrenia".Behavioral Science.9 (4): 371.doi:10.1002/bs.3830090407.
^Jaenisch R, Bird A (March 2003). "Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals".Nature Genetics.33 (Suppl):245–254.doi:10.1038/ng1089.PMID12610534.S2CID17270515.
^Griffiths AJ, Miller JH, Suzuki DT, Lewontin RC, Gelbart, eds. (2000)."Induced mutations".An Introduction to Genetic Analysis (7th ed.). New York: W. H. Freeman.ISBN978-0-7167-3520-5.
^Griffiths AJ, Miller JH, Suzuki DT, Lewontin RC, Gelbart, eds. (2000)."Selection".An Introduction to Genetic Analysis (7th ed.). New York: W. H. Freeman.ISBN978-0-7167-3520-5.
^Gavrilets S (October 2003). "Perspective: models of speciation: what have we learned in 40 years?".Evolution; International Journal of Organic Evolution.57 (10):2197–2215.doi:10.1554/02-727.PMID14628909.S2CID198158082.
^Frank SA (October 2004). "Genetic predisposition to cancer - insights from population genetics".Nature Reviews. Genetics.5 (10):764–772.doi:10.1038/nrg1450.PMID15510167.S2CID6049662.
.jpg)
