Gregor Mendel, a scientist and Augustinian friar, discovered genetics in the late 19th-century. Mendel studied "trait inheritance", patterns in the way traits are handed down from parents to offspring. 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 and molecular inheritance mechanisms of genes are still primary principles of genetics in the 21st century, but modern genetics has expanded beyond inheritance to studying the function and behavior of genes. Gene structure and function, variation, and distribution are studied within the context of the cell, the organism (e.g. dominance), and within the context of a population. Genetics has given rise to a number of subfields, including epigenetics and population genetics. Organisms studied within the broad field span the domains of life (archaea, bacteria, and eukarya).
Genetic processes work in combination with an organism's environment and experiences to influence development and behavior, often referred to as nature versus nurture. The intracellular or extracellular environment of a cell or organism may switch gene transcription on or off. A classic example is two seeds of genetically identical corn, one placed in a temperate climate and one in an arid climate. While the average height of the two corn stalks may be genetically determined to be equal, 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 observation that living things inherit traits from their parents has been used since prehistoric times to improve crop plants and animals through selective breeding. The modern science of genetics, seeking to understand this process, began with the work of the Augustinian friar Gregor Mendel in the mid-19th century.
Prior to Mendel, Imre Festetics, a Hungarian noble, who lived in Kőszeg before Mendel, was the first who used the word "genetics." He described several rules of genetic inheritance in his work The genetic law of the Nature (Die genetische Gesätze der Natur, 1819). His second law is the same as what Mendel published. In his third law, he developed the basic principles of mutation (he can be considered a forerunner of Hugo de Vries).
Other theories of inheritance preceded Mendel's work. A popular theory during the 19th century, and implied by Charles Darwin's 1859 On the Origin of Species, was blending inheritance: the idea that individuals inherit a smooth blend of traits from their parents. 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 with quantitative effects. Another theory that had some support at that time was the inheritance of acquired characteristics: the belief that individuals inherit traits strengthened by their parents. This theory (commonly associated with Jean-Baptiste Lamarck) is now known to be wrong—the experiences of individuals do not affect the genes they pass to their children, although evidence in the field of epigenetics has revived some aspects of Lamarck's theory. Other theories included the pangenesis of Charles Darwin (which had both acquired and inherited aspects) and Francis Galton's reformulation of pangenesis as both particulate and inherited.
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 the Naturforschender Verein (Society for Research in Nature) in Brünn, 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.
The importance of Mendel's work did not gain wide understanding until 1900, after his death, when Hugo de Vries and other scientists rediscovered his research. William Bateson, a proponent of Mendel's work, coined the word genetics in 1905 (the adjective genetic, derived from the Greek word genesis—γένεσις, "origin", predates the noun and was first used in a biological sense in 1860). Bateson both acted as a mentor and was aided significantly by the work of other scientists from Newnham College at Cambridge, specifically the work of Becky Saunders, Nora Darwin Barlow, and Muriel Wheldale Onslow. Bateson popularized the usage of the word genetics to describe the study of inheritance in his inaugural address to the Third International Conference on Plant Hybridization in London in 1906.
After the rediscovery of Mendel's work, scientists tried to determine which molecules in the cell were responsible for inheritance. In 1911, Thomas Hunt Morgan argued that genes are on chromosomes, based on observations of a sex-linked white eye mutation in fruit flies. In 1913, his student Alfred Sturtevant used the phenomenon of genetic linkage to show that genes are arranged linearly on the chromosome.
Although genes were known to exist on chromosomes, chromosomes are composed of both protein and DNA, and scientists did not know which of the two is responsible for inheritance. In 1928, Frederick Griffith discovered the phenomenon of transformation (see Griffith's experiment): dead bacteria could transfer genetic material to "transform" other still-living bacteria. Sixteen years later, in 1944, the Avery–MacLeod–McCarty experiment identified DNA as the molecule responsible for transformation. The role of the nucleus as the repository of genetic information in eukaryotes had been established by Hämmerling in 1943 in his work on the single celled alga Acetabularia. The Hershey–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.
James Watson and Francis Crick determined the structure of DNA in 1953, using the X-ray crystallography work of Rosalind Franklin and Maurice Wilkins that indicated DNA has a helical structure (i.e., shaped like a corkscrew). 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. This structure showed that genetic information exists in the sequence of nucleotides on each strand of DNA. The structure also suggested a simple method for replication: 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.
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 of protein production. It was discovered that the cell uses DNA as a template to create matching messenger RNA, molecules with nucleotides very similar to DNA. The nucleotide sequence of a messenger RNA is used to create an amino acid sequence in protein; this translation between nucleotide sequences and amino acid sequences is known as the genetic code.
With the newfound molecular understanding of inheritance came an explosion of research. A notable theory arose from Tomoko Ohta in 1973 with her amendment to the neutral theory of molecular evolution through publishing the nearly neutral theory of molecular evolution. In this theory, Ohta stressed the importance of natural selection and the environment to the rate at which genetic evolution occurs. One important development was chain-termination DNA sequencing in 1977 by Frederick Sanger. This technology allows scientists to read the nucleotide sequence of a DNA molecule. In 1983, Kary Banks Mullis developed the polymerase chain reaction, providing a quick way to isolate and amplify a specific section of DNA from a mixture. The efforts of the Human Genome Project, Department of Energy, NIH, and parallel private efforts by Celera Genomics led to the sequencing of the human genome in 2003.
At its most fundamental level, inheritance in organisms occurs by passing discrete heritable units, called genes, from parents to offspring. This property was first observed by Gregor Mendel, who studied the segregation of heritable traits in pea plants. In his experiments studying the trait for flower color, Mendel observed that the flowers of each pea plant were either purple or white—but never an intermediate between the two colors. These different, discrete versions of the same gene are called alleles.
In the case of the pea, which is a diploid species, each individual plant has two copies of each gene, one copy inherited from each parent. Many species, including humans, have this pattern of inheritance. Diploid organisms with two copies of the same allele of a given gene are called homozygous at that gene locus, while organisms with two different alleles of a given gene are called heterozygous.
The set of alleles for a given organism is called its genotype, while the observable traits of the organism are called its phenotype. When organisms are heterozygous at a gene, often one allele is called dominant as its qualities dominate the phenotype of the organism, while the other allele is called recessive as its qualities recede and are not observed. Some alleles do not have complete dominance and instead have incomplete dominance by expressing an intermediate phenotype, or codominance by expressing both alleles at once.
When a pair of organisms reproduce 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 as Mendel's first law or the Law of Segregation.
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 the Punnett square.
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" or the "law of independent assortment," means that the alleles of different genes get shuffled between parents to form offspring with many different combinations. (Some genes do not assort independently, demonstrating genetic linkage, a topic discussed later in this article.)
Often different genes can interact in a way that influences the same trait. In the Blue-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 called epistasis, with the second gene epistatic to the first.
Many traits are not discrete features (e.g. purple or white flowers) but are instead continuous features (e.g. human height and skin color). These complex traits are products of many genes. 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 called heritability. 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 and health care, height has a heritability of only 62%.
The molecular basis for genes is deoxyribonucleic acid (DNA). DNA is composed of a chain of nucleotides, of which there are four types: adenine (A), cytosine (C), guanine (G), and thymine (T). Genetic information exists in the sequence of these nucleotides, and genes exist as stretches of sequence along the DNA chain. Viruses are the only exception to this rule—sometimes viruses use the very similar molecule RNA instead of DNA as their genetic material. Viruses cannot reproduce without a host and are unaffected by many genetic processes, so tend not to be considered living organisms.
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.
Genes are arranged linearly along long chains of DNA base-pair sequences. In bacteria, each cell usually contains a single circular genophore, while 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 pairs in length. 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 nucleosomes, segments of DNA wound around cores of histone proteins. The full set of hereditary material in an organism (usually the combined DNA sequences of all chromosomes) is called the genome.
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 loci of the two homologous chromosomes, each allele inherited from a different parent.
Many species have so-called sex chromosomes that determine the gender of each organism. 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. The X and Y chromosomes form a strongly heterogeneous pair.
When cells divide, their full genome is copied and each 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 clones.
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). 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 gametes such as sperm or eggs.
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 conjugation, transferring a small circular piece of DNA to another bacterium. Bacteria can also take up raw DNA fragments found in the environment and integrate them into their genomes, a phenomenon known as transformation. These processes result in horizontal gene transfer, transmitting fragments of genetic information between organisms that would be otherwise unrelated.
The diploid nature of chromosomes allows for genes on different chromosomes to 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. This process of chromosomal crossover generally occurs during meiosis, a series of cell divisions that creates haploid cells.
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.
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. 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 linkage map that roughly describes the arrangement of the genes along the chromosome.
Genes generally express their functional effect through the production of proteins, which are complex molecules responsible for most functions in the cell. Proteins are made up of one or more polypeptide chains, each of which is composed of a sequence of amino acids, and the DNA sequence of a gene (through an RNA intermediate) is used to produce a specific 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.
This messenger RNA molecule is then used to produce a corresponding amino acid sequence through a process called 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 instruction to end the amino acid sequence; this correspondence is called the genetic code. 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.
The specific sequence of amino acids results in a unique three-dimensional structure for that protein, and the three-dimensional structures of proteins are related to their functions. 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 enzymes by facilitating chemical reactions 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.
A 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 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. Sickle-cell versions of hemoglobin stick to themselves, stacking to form fibers that distort the shape of red blood cells carrying the protein. These sickle-shaped cells no longer flow smoothly through blood vessels, having a tendency to clog or degrade, causing the medical problems associated with this disease.
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 (e.g. microRNA).
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. 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 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—so the cat has dark hair at its extremities.
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.
A common method for determining how genes and environment ("nature and nurture") contribute to a phenotype involves studying identical and fraternal twins, or other siblings of multiple births. 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 identical quadruplets all diagnosed with schizophrenia. However, such tests cannot separate genetic factors from environmental factors affecting fetal development.
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. 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 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.
Differences in gene expression are especially clear within multicellular 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 and intercellular signals and gradually establishing different patterns of gene expression to create different behaviors. As no single gene is responsible for the development of structures within multicellular organisms, these patterns arise from the complex interactions between many cells.
Within eukaryotes, 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. 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 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.
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 of DNA polymerases. Processes that increase the rate of changes in DNA are called mutagenic: mutagenic chemicals promote errors in DNA replication, often by interfering with the structure of base-pairing, while UV radiation induces mutations by causing damage to the DNA structure. Chemical damage to DNA occurs naturally as well and cells use DNA repair mechanisms to repair mismatches and breaks. The repair does not, however, always restore the original sequence.
In organisms that use chromosomal 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).
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 reproductive fitness. Mutations that do have an effect are usually detrimental, but occasionally some can be beneficial. Studies in the fly Drosophila melanogaster suggest that if a mutation changes a protein produced by a gene, about 70 percent of these mutations will be harmful with the remainder being either neutral or weakly beneficial.
Population genetics studies the distribution of genetic differences within populations and how these distributions change over time. Changes in the frequency of an allele in a population are mainly influenced by natural selection, where a given allele provides a selective or reproductive advantage to the organism, as well as other factors such as mutation, genetic drift, genetic hitchhiking, artificial selection and migration.
Over many generations, the genomes of organisms can change significantly, resulting in evolution. In the process called adaptation, selection for beneficial mutations can cause a species to evolve into forms better able to survive in their environment. New species are formed through the process of speciation, often caused by geographical separations that prevent populations from exchanging genes with each other.
By comparing the homology between different species' genomes, it is possible to calculate the evolutionary distance between them and when 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 form evolutionary trees; these trees represent the common descent and divergence of species over time, although they do not show the transfer of genetic material between unrelated species (known as horizontal gene transfer and most common in bacteria).
Although geneticists originally studied inheritance in a wide range of organisms, researchers began to specialize in studying the genetics of a particular subset of organisms. The fact that significant research already existed for a given organism would encourage new researchers to choose it for further study, and so eventually a few model organisms became the basis for most genetics research. Common research topics in model organism genetics include the study of gene regulation and the involvement of genes in development and cancer.
Organisms were chosen, in part, for convenience—short generation times and easy genetic manipulation made some organisms popular genetics research tools. Widely used model organisms include the gut bacterium Escherichia coli, the plant Arabidopsis thaliana, baker's yeast (Saccharomyces cerevisiae), the nematode Caenorhabditis elegans, the common fruit fly (Drosophila melanogaster), and the common house mouse (Mus musculus).
Medical genetics seeks to understand how genetic variation relates to human health and disease. When searching for an unknown gene that may be involved in a disease, researchers commonly use genetic linkage and genetic pedigree charts to find the location on the genome associated with the disease. At the population level, researchers take advantage of Mendelian randomization to look for locations in the genome that are associated with diseases, a method especially useful for multigenic traits not clearly defined by a single gene. Once a candidate gene is found, further research is often done on the corresponding (or homologous) genes of model organisms. In addition to studying genetic diseases, the increased availability of genotyping methods has led to the field of pharmacogenetics: the study of how genotype can affect drug responses.
Individuals differ in their inherited tendency to develop cancer, 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 trigger cell death, but sometimes additional mutations occur that cause cells to ignore these messages. An internal process of natural selection occurs within the body and eventually mutations accumulate within cells to promote their own growth, creating a cancerous tumor that grows and invades various tissues of the body.
Normally, a cell divides only in response to signals called growth factors and stops 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 the epithelium 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 the primary 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 deadly metastasis. 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 of p53 protein, a tumor suppressor, or in the p53 pathway, and gain of function mutations in the Ras proteins, or in other oncogenes.
DNA can be manipulated in the laboratory. Restriction enzymes are commonly used enzymes that cut DNA at specific sequences, producing predictable fragments of DNA. DNA fragments can be visualized through use of gel electrophoresis, which separates fragments according to their length.
The use of ligation enzymes allows DNA fragments to be connected. By binding ("ligating") fragments of DNA together from different sources, researchers can create recombinant DNA, the DNA often associated with genetically modified organisms. Recombinant DNA is commonly used in the context of plasmids: short circular DNA molecules with a few genes on them. In the process known as molecular cloning, researchers can amplify the DNA fragments by inserting plasmids into bacteria and then culturing them on plates of agar (to isolate clones of bacteria cells—"cloning" can also refer to the various means of creating cloned ("clonal") organisms).
DNA can also be amplified using a procedure called the polymerase chain reaction (PCR). 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.
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 of chain-termination sequencing, developed in 1977 by a team led by Frederick 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.
As sequencing has become less expensive, researchers have sequenced the genomes of many organisms using a process called genome assembly, which utilizes computational tools to stitch together sequences from many different fragments. These technologies were used to sequence the human genome in the Human Genome Project completed in 2003. New high-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.
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. The large amount of sequence data available has created the field of genomics, research that uses computational tools to search for and analyze patterns in the full genomes of organisms. Genomics can also be considered a subfield of bioinformatics, which uses computational approaches to analyze large sets of biological data. A common problem to these fields of research is how to manage and share data that deals with human subject and personally identifiable information. See also genomics data sharing.
On 19 March 2015, a group of leading biologists urged a worldwide ban on clinical use of methods, particularly the use of CRISPR and zinc finger, to edit the human genome in a way that can be inherited. In April 2015, Chinese researchers reported results of basic research to edit the DNA of non-viable human embryos using CRISPR.
An allele () is a variant form of a given gene. Sometimes, the presence of different alleles of the same gene can result in different observable phenotypic traits, such as different pigmentation. A notable example of this trait of color variation is Gregor Mendel's discovery that the white and purple flower colors in pea plants were the result of "pure line" traits which could be used as a control for future experiments. However, most genetic variations result in little or no observable variation.
Most multicellular organisms have two sets of chromosomes; that is, they are diploid. In this case the chromosomes can be paired: each pair is made up of two chromosomes of the same type, known as homologous chromosomes. If both alleles at a gene (or locus) on the homologous chromosomes are the same, they and the organism are homozygous with respect to that gene (or locus). If the alleles are different, they and the organism are heterozygous with respect to that gene.Bay (horse)
Bay is a hair coat color of horses, characterized by a brown body color with a black mane, tail, ear edges, and lower legs. Bay is one of the most common coat colors in many horse breeds.
The black areas of a bay horse's hair coat are called "black points", and without them, a horse cannot be considered a bay horse. Black points may sometimes be covered by white markings; however such markings do not alter a horse's classification as "bay". Bay horses have dark skin, except under white markings - where the skin is pink. Genetically, bay occurs when a horse carries both the Agouti gene and a black base coat. The addition of other genes creates many additional coat colors. While the basic concepts behind bay coloring are fairly simple, the genes themselves and the mechanisms that cause shade variations within the bay family are quite complex and, at times, disputed. The genetics of dark shades of bay are still under study. A DNA test said to detect the seal brown (At) allele was developed, but subsequently pulled from the market. Sooty genetics also appear to darken some horses' bay coats, and that genetic mechanism is yet to be fully understood.Behavioural genetics
Behavioural genetics, also referred to as behaviour genetics, is a field of scientific research that uses genetic methods to investigate the nature and origins of individual differences in behaviour. While the name "behavioural genetics" connotes a focus on genetic influences, the field broadly investigates genetic and environmental influences, using research designs that allow removal of the confounding of genes and environment. Behavioural genetics was founded as a scientific discipline by Francis Galton in the late 19th century, only to be discredited through association with eugenics movements before and during World War II. In the latter half of the 20th century, the field saw renewed prominence with research on inheritance of behaviour and mental illness in humans (typically using twin and family studies), as well as research on genetically informative model organisms through selective breeding and crosses. In the late 20th and early 21st centuries, technological advances in molecular genetics made it possible to measure and modify the genome directly. This led to major advances in model organism research (e.g., knockout mice) and in human studies (e.g., genome-wide association studies), leading to new scientific discoveries.
Findings from behavioural genetic research have broadly impacted modern understanding of the role of genetic and environmental influences on behaviour. These include evidence that nearly all researched behaviors are under a significant degree of genetic influence, and that influence tends to increase as individuals develop into adulthood. Further, most researched human behaviours are influenced by a very large number of genes and the individual effects of these genes are very small. Environmental influences also play a strong role, but they tend to make family members more different from one another, not more similar.Dominance (genetics)
Dominance in genetics is a relationship between alleles of one gene, in which the effect on phenotype of one allele masks the contribution of a second allele at the same locus. The first allele is dominant and the second allele is recessive. For genes on an autosome (any chromosome other than a sex chromosome), the alleles and their associated traits are autosomal dominant or autosomal recessive. Dominance is a key concept in Mendelian inheritance and classical genetics. Often the dominant allele codes for a functional protein whereas the recessive allele does not.
A classic example of dominance is the inheritance of seed shape in peas. Peas may be round, associated with allele R, or wrinkled, associated with allele r. In this case, three combinations of alleles (genotypes) are possible: RR, Rr, and rr. The RR individuals have round peas and the rr individuals have wrinkled peas. In Rr individuals the R allele masks the presence of the r allele, so these individuals also have round peas. Thus, allele R is dominant to allele r, and allele r is recessive to allele R. This use of upper case letters for dominant alleles and lower case ones for recessive alleles is a widely followed convention.
More generally, where a gene exists in two allelic versions (designated A and a), three combinations of alleles are possible: AA, Aa, and aa. If AA and aa individuals (homozygotes) show different forms of some trait (phenotypes), and Aa individuals (heterozygotes) show the same phenotype as AA individuals, then allele A is said to dominate, be dominant to or show dominance to allele a, and a is said to be recessive to A.
Dominance is not inherent to either an allele or its phenotype. It is a relationship between two alleles of a gene and their associated phenotypes; one allele can be dominant over a second allele, recessive to a third allele, and codominant to a fourth. Also, an allele may be dominant for a particular aspect of phenotype but not for other aspects influenced by the same gene. Dominance differs from epistasis, a relationship in which an allele of one gene affects the expression of another allele at a different gene.Genetic disorder
A genetic disorder is a genetic problem caused by one or more abnormalities formed in the genome. Most genetic disorders are quite rare and affect one person in every several thousands or millions. The earliest known genetic condition in a hominid was in the fossil species Paranthropus robustus, with over a third of individuals displaying Amelogenesis imperfecta.Genetic disorders may be hereditary, meaning that they are passed down from the parents' genes. In other genetic disorders, defects may be caused by new mutations or changes to the DNA. In such cases, the defect will only be passed down if it occurs in the germline.
Some types of recessive gene disorders confer an advantage in certain environments when only one copy of the gene is present.Geneticist
A geneticist is a biologist who studies genetics, the science of genes, heredity, and variation of organisms.Gregor Mendel
Gregor Johann Mendel (Czech: Řehoř Jan Mendel; 20 July 1822 – 6 January 1884) (English: ) was a scientist, Augustinian friar and abbot of St. Thomas' Abbey in Brno, Margraviate of Moravia. Mendel was born in a German-speaking family in the Silesian part of the Austrian Empire (today's Czech Republic) and gained posthumous recognition as the founder of the modern science of genetics. Though farmers had known for millennia that crossbreeding of animals and plants could favor certain desirable traits, Mendel's pea plant experiments conducted between 1856 and 1863 established many of the rules of heredity, now referred to as the laws of Mendelian inheritance.Mendel worked with seven characteristics of pea plants: plant height, pod shape and color, seed shape and color, and flower position and color. Taking seed color as an example, Mendel showed that when a true-breeding yellow pea and a true-breeding green pea were cross-bred their offspring always produced yellow seeds. However, in the next generation, the green peas reappeared at a ratio of 1 green to 3 yellow. To explain this phenomenon, Mendel coined the terms “recessive” and “dominant” in reference to certain traits. (In the preceding example, the green trait, which seems to have vanished in the first filial generation, is recessive and the yellow is dominant.) He published his work in 1866, demonstrating the actions of invisible “factors”—now called genes—in predictably determining the traits of an organism.
The profound significance of Mendel's work was not recognized until the turn of the 20th century (more than three decades later) with the rediscovery of his laws. Erich von Tschermak, Hugo de Vries, Carl Correns and William Jasper Spillman independently verified several of Mendel's experimental findings, ushering in the modern age of genetics.Heredity
Heredity is the passing on of traits from parents to their offspring, either through asexual reproduction or sexual reproduction, the offspring cells or organisms acquire the genetic information of their parents. Through heredity, variations between individuals can accumulate and cause species to evolve by natural selection. The study of heredity in biology is genetics.Hybrid (biology)
In biology, a hybrid is the offspring resulting from combining the qualities of two organisms of different breeds, varieties, species or genera through sexual reproduction. Hybrids are not always intermediates between their parents (such as in blending inheritance), but can show hybrid vigour, sometimes growing larger or taller than either parent. The concept of a hybrid is interpreted differently in animal and plant breeding, where there is interest in the individual parentage. In genetics, attention is focused on the numbers of chromosomes. In taxonomy, a key question is how closely related the parent species are.
Species are reproductively isolated by strong barriers to hybridisation, which include morphological differences, differing times of fertility, mating behaviors and cues, and physiological rejection of sperm cells or the developing embryo. Some act before fertilization and others after it. Similar barriers exist in plants, with differences in flowering times, pollen vectors, inhibition of pollen tube growth, somatoplastic sterility, cytoplasmic-genic male sterility and the structure of the chromosomes. A few animal species and many plant species, however, are the result of hybrid speciation, including important crop plants such as wheat, where the number of chromosomes has been doubled.
Human impact on the environment has resulted in an increase in the interbreeding between regional species, and the proliferation of introduced species worldwide has also resulted in an increase in hybridisation. This genetic mixing may threaten many species with extinction, while genetic erosion in crop plants may be damaging the gene pools of many species for future breeding. A form of often intentional human-mediated hybridisation is the crossing of wild and domesticated species. This is common in both traditional horticulture and modern agriculture; many commercially useful fruits, flowers, garden herbs, and trees have been produced by hybridisation. One such flower, Oenothera lamarckiana, was central to early genetics research into mutationism and polyploidy. It is also more occasionally done in the livestock and pet trades; some well-known wild × domestic hybrids are beefalo and wolfdogs. Human selective breeding of domesticated animals and plants has resulted is the development of distinct breeds (usually called cultivars in reference to plants); crossbreeds between them (without any wild stock) are sometimes also imprecisely referred to as "hybrids".
Hybrid humans existed in prehistory. For example, Neanderthals and anatomically modern humans are thought to have interbred as recently as 40,000 years ago.
Mythological hybrids appear in human culture in forms as diverse as the Minotaur, blends of animals, humans and mythical beasts such as centaurs and sphinxes, and the Nephilim of the Biblical apocrypha described as the wicked sons of fallen angels and attractive women.Locus (genetics)
A locus (plural loci) in genetics is a fixed position on a chromosome, like the position of a gene or a marker (genetic marker). Each chromosome carries many genes; human's estimated 'haploid' protein coding genes are 19,000–20,000, on the 23 different chromosomes. A variant of the similar DNA sequence located at a given locus is called an allele. The ordered list of loci known for a particular genome is called a gene map. Gene mapping is the process of determining the locus for a particular biological trait.
Diploid and polyploid cells whose chromosomes have the same allele of a given gene at some locus are called homozygous with respect to that gene, while those that have different alleles of a given gene at a locus are called heterozygous with respect to that gene.Medical genetics
Medical genetics is the branch of medicine that involves the diagnosis and management of hereditary disorders. Medical genetics differs from human genetics in that human genetics is a field of scientific research that may or may not apply to medicine, while medical genetics refers to the application of genetics to medical care. For example, research on the causes and inheritance of genetic disorders would be considered within both human genetics and medical genetics, while the diagnosis, management, and counselling people with genetic disorders would be considered part of medical genetics.
In contrast, the study of typically non-medical phenotypes such as the genetics of eye color would be considered part of human genetics, but not necessarily relevant to medical genetics (except in situations such as albinism). Genetic medicine is a newer term for medical genetics and incorporates areas such as gene therapy, personalized medicine, and the rapidly emerging new medical specialty, predictive medicine.Mendelian inheritance
Mendelian inheritance is a type of biological inheritance that follows the laws originally proposed by Gregor Mendel in 1865 and 1866 and re-discovered in 1900. These laws were initially controversial. When Mendel's theories were integrated with the Boveri–Sutton chromosome theory of inheritance by Thomas Hunt Morgan in 1915, they became the core of classical genetics. Ronald Fisher combined these ideas with the theory of natural selection in his 1930 book The Genetical Theory of Natural Selection, putting evolution onto a mathematical footing and forming the basis for population genetics within the modern evolutionary synthesis.Molecular biology
Molecular biology is a branch of biology that concerns the molecular basis of biological activity between biomolecules in the various systems of a cell, including the interactions between DNA, RNA, proteins and their biosynthesis, as well as the regulation of these interactions. Writing in Nature in 1961, William Astbury described molecular biology as:
...not so much a technique as an approach, an approach from the viewpoint of the so-called basic sciences with the leading idea of searching below the large-scale manifestations of classical biology for the corresponding molecular plan. It is concerned particularly with the forms of biological molecules and [...] is predominantly three-dimensional and structural – which does not mean, however, that it is merely a refinement of morphology. It must at the same time inquire into genesis and function.Mutation
In biology, a mutation is the alteration of the nucleotide sequence of the genome of an organism, virus, or extrachromosomal DNA.Mutations result from errors during DNA replication (especially during meiosis) or other types of damage to DNA (such as may be caused by exposure to radiation or carcinogens), which then may undergo error-prone repair (especially microhomology-mediated end joining), or cause an error during other forms of repair, or else may cause an error during replication (translesion synthesis). Mutations may also result from insertion or deletion of segments of DNA due to mobile genetic elements. Mutations may or may not produce discernible changes in the observable characteristics (phenotype) of an organism. Mutations play a part in both normal and abnormal biological processes including: evolution, cancer, and the development of the immune system, including junctional diversity.
The genomes of RNA viruses are based on RNA rather than DNA. The RNA viral genome can be double-stranded (as in DNA) or single-stranded. In some of these viruses (such as the single-stranded human immunodeficiency virus) replication occurs quickly and there are no mechanisms to check the genome for accuracy. This error-prone process often results in mutations.
Mutation can result in many different types of change in sequences. Mutations in genes can either have no effect, alter the product of a gene, or prevent the gene from functioning properly or completely. Mutations can also occur in nongenic regions. One study on genetic variations between different species of Drosophila suggests that, if a mutation changes a protein produced by a gene, the result is likely to be harmful, with an estimated 70 percent of amino acid polymorphisms that have damaging effects, and the remainder being either neutral or marginally beneficial. Due to the damaging effects that mutations can have on genes, organisms have mechanisms such as DNA repair to prevent or correct mutations by reverting the mutated sequence back to its original state.Natural selection
Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the heritable traits characteristic of a population over generations. Charles Darwin popularised the term "natural selection", contrasting it with artificial selection, which in his view is intentional, whereas natural selection is not.
Variation exists within all populations of organisms. This occurs partly because random mutations arise in the genome of an individual organism, and offspring can inherit such mutations. Throughout the lives of the individuals, their genomes interact with their environments to cause variations in traits. The environment of a genome includes the molecular biology in the cell, other cells, other individuals, populations, species, as well as the abiotic environment. Because individuals with certain variants of the trait tend to survive and reproduce more than individuals with other, less successful variants, the population evolves. Other factors affecting reproductive success include sexual selection (now often included in natural selection) and fecundity selection.
Natural selection acts on the phenotype, the characteristics of the organism which actually interact with the environment, but the genetic
(heritable) basis of any phenotype that gives that phenotype a reproductive advantage may become more common in a population. Over time, this process can result in populations that specialise for particular ecological niches (microevolution) and may eventually result in speciation (the emergence of new species, macroevolution). In other words, natural selection is a key process in the evolution of a population.
Natural selection is a cornerstone of modern biology. The concept, published by Darwin and Alfred Russel Wallace in a joint presentation of papers in 1858, was elaborated in Darwin's influential 1859 book On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life. He described natural selection as analogous to artificial selection, a process by which animals and plants with traits considered desirable by human breeders are systematically favoured for reproduction. The concept of natural selection originally developed in the absence of a valid theory of heredity; at the time of Darwin's writing, science had yet to develop modern theories of genetics. The union of traditional Darwinian evolution with subsequent discoveries in classical genetics formed the modern synthesis of the mid-20th century. The addition of molecular genetics has led to evolutionary developmental biology, which explains evolution at the molecular level. While genotypes can slowly change by random genetic drift, natural selection remains the primary explanation for adaptive evolution.Population genetics
Population genetics is a subfield of genetics that deals with genetic differences within and between populations, and is a part of evolutionary biology. Studies in this branch of biology examine such phenomena as adaptation, speciation, and population structure.Population genetics was a vital ingredient in the emergence of the modern evolutionary synthesis. Its primary founders were Sewall Wright, J. B. S. Haldane and Ronald Fisher, who also laid the foundations for the related discipline of quantitative genetics. Traditionally a highly mathematical discipline, modern population genetics encompasses theoretical, lab, and field work. Population genetic models are used both for statistical inference from DNA sequence data and for proof/disproof of concept.What sets population genetics apart today from newer, more phenotypic approaches to modelling evolution, such as evolutionary game theory and adaptive dynamics, is its emphasis on genetic phenomena as dominance, epistasis, and the degree to which genetic recombination breaks up linkage disequilibrium. This makes it appropriate for comparison to population genomics data.Promoter (genetics)
In genetics, a promoter is a region of DNA that initiates transcription of a particular gene. Promoters are located near the transcription start sites of genes, on the same strand and upstream on the DNA (towards the 3' region of the anti-sense strand).
Promoters can be about 100–1000 base pairs long.Ukrainians
Ukrainians (Ukrainian: українці, ukrayintsi, [ukrɑˈjinʲtsʲi]) are an East Slavic ethnic group native to Ukraine, which is by total population the seventh-largest nation in Europe. The Constitution of Ukraine applies the term 'Ukrainians' to all its citizens. The people of Ukraine have historically been known as "Rusyns (Ruthenians)" and "Cossacks", among others. According to most dictionary definitions, a descriptive name for the "inhabitants of Ukraine" is Ukrainian or Ukrainian people.Zygosity
Zygosity (the noun, zygote, is from the Greek zygotos "yoked," from zygon "yoke") () is the degree of similarity of the alleles for a trait in an organism.
Most eukaryotes have two matching sets of chromosomes; that is, they are diploid. Diploid organisms have the same loci on each of their two sets of homologous chromosomes except that the sequences at these loci may differ between the two chromosomes in a matching pair and that a few chromosomes may be mismatched as part of a chromosomal sex-determination system. If both alleles of a diploid organism are the same, the organism is homozygous at that locus. If they are different, the organism is heterozygous at that locus. If one allele is missing, it is hemizygous, and, if both alleles are missing, it is nullizygous.
The DNA sequence of a gene often varies from one individual to another. Those variations are called alleles. While some genes have only one allele because there is low variation, others have only one allele because deviation from that allele can be harmful or fatal. But most genes have two or more alleles. The frequency of different alleles varies throughout the population. Some genes may have two alleles with equal distribution. For other genes, one allele may be common, and another allele may be rare. Sometimes, one allele is a disease-causing variation while the other allele is healthy. Sometimes, the different variations in the alleles make no difference at all in the function of the organism.
In diploid organisms, one allele is inherited from the male parent and one from the female parent. Zygosity is a description of whether those two alleles have identical or different DNA sequences. In some cases the term "zygosity" is used in the context of a single chromosome.
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