Gene

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Genes are the units of heredity in living organisms. They are encoded in the organism's genetic material (usually DNA or RNA), and control the physical development and behavior of the organism. During reproduction, the genetic material is passed on from the parent(s) to the offspring. Genetic material can also be passed between un-related individuals (e.g. via transfection, or on viruses). Genes encode the information necessary to construct the chemicals (proteins etc.) needed for the organism to function.

The word "gene" was coined in 1909 by Danish botanist Wilhelm Johannsen for the fundamental physical and functional unit of heredity. The word gene was derived from Hugo De Vries' term pangen, itself a derivative of the word pangenesis which Darwin (1868) had coined. The word pangenesis is made from the Greek words pan (a prefix meaning "whole", "encompassing") and genesis ("birth") or genos ("origin").

The term "gene" is shared by many disciplines, including classical genetics, molecular genetics, evolutionary biology and population genetics. Because each discipline models the biology of life differently, the usage of the word gene varies between disciplines. It may refer to either material or conceptual entities.

Following the discovery that DNA is the genetic material, the growth of biotechnology, and the project to sequence the human genome, the common usage of the word "gene" has increasingly reflected its meaning in molecular biology, namely the segments of DNA which cells transcribe into RNA and translate, at least in part, into proteins. The Sequence Ontology project defines a gene as: "A locatable region of genomic sequence, corresponding to a unit of inheritance, which is associated with regulatory regions, transcribed regions and/or other functional sequence regions".

In common speech, "gene" is often used to refer to the hereditary cause of a trait, disease or condition—as in "the gene for obesity." Speaking more precisely, a biologist might refer to an allele or a mutation that has been implicated in or is associated with obesity. This is because biologists know that many factors other than genes decide whether a person is obese or not: eating habits, exercise, prenatal environment, upbringing, culture and the availability of food, for example.

Moreover, it is very unlikely that variations within a single gene—or single genetic locus—fully determine one's genetic predisposition for obesity. These aspects of inheritance—the interplay between genes and environment, the influence of many genes—appear to be the norm with regard to many and perhaps most ("complex" or "multi-factoral") traits. The term phenotype refers to the characteristics that result from this interplay (see genotype-phenotype distinction).

Overview

Properties of genes

In molecular biology, a gene is considered to be the region of DNA (or RNA, in the case of some viruses) that determines the structure of a protein (the coding sequence), together with the region of DNA that controls when and where the protein will be produced (the regulatory sequence). The genetic code determines how the coding DNA sequence is converted into a protein sequence (transcription and translation). The genetic code is essentially the same for all known life, from bacteria to humans.

Through the proteins they encode, genes govern the cells in which they reside. In multicellular organisms, they control the development of the individual from the fertilized egg and the day-to-day functions of the cells that make up tissues and organs. The instrumental roles of their protein products range from mechanical support of the cell structure to the transportation and manufacture of other molecules and to the regulation of other proteins' activities.

The genes that exist today are those that have reproduced successfully in the past. Often, many individual organisms share a gene; thus, the death of an individual need not mean the extinction of the gene. Indeed, if the sacrifice of one individual enhances the survivability of other individuals with the same gene, the death of an individual may enhance the overall survival of the gene. This is the basis of the selfish gene view, popularized by Richard Dawkins. He points out in his book, The Selfish Gene, that to be successful genes need have no other "purpose" than to propagate themselves, even at the expense of their host organism's welfare. A human that behaved in such a way would be described as "selfish", although, ironically, a selfish gene may promote altruistic behaviours. According to Dawkins, the possibly disappointing answer to the question "what is the meaning of life?" may be "the survival and perpetuation of ribonucleic acids and their associated proteins".

Types of genes

Due to rare, spontaneous errors (e.g. in DNA replication), mutations in the sequence of a gene may arise. Once propagated to the next generation, this mutation may lead to variations within a species' population. Variants of a single gene are known as alleles, and differences in alleles may give rise to differences in traits, for example eye colour. A gene's most common allele is called the wild type allele, and rare alleles are called mutants.

In most cases, RNA is an intermediate product in the process of manufacturing proteins from genes. However, for some gene sequences, the RNA molecules are the actual functional products. For example, RNAs known as ribozymes are capable of enzymatic function, and small interfering RNAs have a regulatory role. The DNA sequences from which such RNAs are transcribed are known as non-coding RNA, or RNA genes.

Most living organisms carry their genes and transmit them to offspring as DNA, but some viruses carry only RNA. Because they use RNA, their cellular hosts may synthesize their proteins as soon as they are infected and without the delay in waiting for transcription. On the other hand, RNA retroviruses, such as HIV, require the reverse transcription of their genome from RNA into DNA before their proteins can be synthesized.

Human gene nomenclature

For each known human gene the HUGO Gene Nomenclature Committee (HGNC) approve a gene name and symbol (short-form abbreviation). All approved symbols are stored in the HGNC Database. Each symbol is unique and each gene is only given one approved gene symbol. It is necessary to provide a unique symbol for each gene so that people can talk about them. This also facilitates electronic data retrieval from publications. In preference each symbol maintains parallel construction in different members of a gene family and can be used in other species, especially the mouse.

Typical numbers of genes in an organism

organism	genes	base pairs
Plant	<50,000	<10¹¹
Human, mouse or rat	25,000	3×10⁹
Fruit Fly	13,767	1.3×10⁸
Honey bee	15,000	3×10⁸
Worm	19,000	9.7×10⁷
Fungus	6,000	1.3×10⁷
Bacterium	500–6,000	5×10⁵–10⁷
Mycoplasma genitalium	500	580,000
DNA virus	10–900	5,000–800,000
RNA virus	1–25	1,000–23,000
Viroid	0–1	~500

The attached table gives typical numbers of genes and genome size for some organisms. Estimates of the number of genes in an organism are somewhat controversial because they depend on the discovery of genes, and no techniques currently exist to prove that a DNA sequence contains no gene. (In early genetics, genes could be identified only if there were mutations, or alleles.) Nonetheless, estimates are made based on current knowledge.

Chemistry and function of genes

Chemical structure of a gene

Four kinds of sequentially linked nucleotides compose a DNA molecule or strand (more at DNA). These four nucleotides constitute the genetic alphabet. A sequence of three consecutive nucleotides, called a codon, is the protein-coding vocabulary. The sequence of codons in a gene specifies the amino-acid sequence of the protein it encodes.

In most eukaryotic species, very little of the DNA in the genome encodes proteins, and the genes may be separated by vast sequences of so-called junk DNA. Moreover, the genes are often fragmented internally by non-coding sequences called introns, which can be many times longer than the coding sequence. Introns are removed on the heels of transcription by splicing. In the primary molecular sense, they represent parts of a gene, however.

All the genes and intervening DNA together make up the genome of an organism, which in many species is divided among several chromosomes and typically present in two or more copies. The location (or locus) of a gene and the chromosome on which it is situated is in a sense arbitrary. Genes that appear together on the chromosomes of one species, such as humans, may appear on separate chromosomes in another species, such as mice. Two genes positioned near one another on a chromosome may encode proteins that figure in the same cellular process or in completely unrelated processes. As an example of the former, many of the genes involved in spermatogenesis reside together on the Y chromosome.

Many species carry more than one copy of their genome within each of their somatic cells. These organisms are called diploid if they have two copies or polyploid if they have more than two copies. In such organisms, the copies are practically never identical. With respect to each gene, the copies that an individual possesses are liable to be distinct alleles, which may act synergistically or antagonistically to generate a trait or phenotype. The ways that gene copies interact are explained by chemical dominance relationships (more at genetics, allele).

Expression of molecular genes

For various reasons, the relationship between DNA strand and a phenotype trait is not direct. The same DNA strand in two different individuals may result in different traits because of the effect of other DNA strands or the environment.

The DNA strand is expressed into a trait only if it is transcribed to RNA. Because the transcription starts from a specific base-pair sequence (a promoter) and stops at another (a terminator), our DNA strand needs to be correctly placed between the two. If not, it is considered as junk DNA, and is not expressed.

Cells regulate the activity of genes in part by increasing or decreasing their rate of transcription. Over the short term, this regulation occurs through the binding or unbinding of proteins, known as transcription factors, to specific non-coding DNA sequences called regulatory elements. Therefore, to be expressed, our DNA strand needs to be properly regulated by other DNA strands.

The DNA strand may also be silenced through DNA methylation or by chemical changes to the protein components of chromosomes (see histone). This is a permanent form of regulation of the transcription.

The RNA is often edited before its translation into a protein. Eukaryotic cells splice the transcripts of a gene, by keeping the exons and removing the introns. Therefore, the DNA strand needs to be in an exon to be expressed. Because of the complexity of the splicing process, one transcribed RNA may be spliced in alternate ways to produce not one but a variety of proteins (alternative splicing) from one pre-mRNA. Prokaryotes produce a similar effect by shifting reading frames during translation.

The translation of RNA into a protein also starts with a specific start and stop sequence.

Once produced, the protein interacts with the many other proteins in the cell, according to the cell metabolism. This interaction finally produces the trait.

This complex process helps explain the different meanings of "gene":

a nucleotide sequence in a DNA strand;
or the transcribed RNA, prior to splicing;
or the transcribed RNA after splicing, i.e. without the introns

The latter meaning of gene is the result of more "material entity" than the first one.

Mutations and evolution

Just as there are many factors influencing the expression of a particular DNA strand, there are many ways to have genetic mutations.

For example, natural variations within regulatory sequences appear to underlie many of the heritable characteristics seen in organisms. The influence of such variations on the trajectory of evolution through natural selection may be as large as or larger than variation in sequences that encode proteins. Thus, though regulatory elements are often distinguished from genes in molecular biology, in effect they satisfy the shared and historical sense of the word. Indeed, a breeder or geneticist, in following the inheritance pattern of a trait, has no immediate way to know whether this pattern arises from coding sequences or regulatory sequences. Typically, he or she will simply attribute it to variations within a gene.

Errors during DNA replication may lead to the duplication of a gene, which may diverge over time. Though the two sequences may remain the same, or be only slightly altered, they are typically regarded as separate genes (i.e. not as alleles of the same gene). The same is true when duplicate sequences appear in different species. Yet, though the alleles of a gene differ in sequence, nevertheless they are regarded as a single gene (occupying a single locus).

History

The existence of genes was first suggested by Gregor Mendel, who, in the 1860s, studied inheritance in pea plants and hypothesized a factor that conveys traits from parent to offspring. Although he did not use the term gene, he explained his results in terms of inherited characteristics. Mendel was also the first to hypothesize independent assortment, the distinction between dominant and recessive traits, the distinction between a heterozygote and homozygote, and the difference between what would later be described as genotype and phenotype. Mendel's concept was finally named when Wilhelm Johannsen coined the word gene in 1909.

In the early 1900s, Mendel's work received renewed attention from scientists. In 1910, Thomas Hunt Morgan showed that genes reside on specific chromosomes. He later showed that genes occupy specific locations on the chromosome. With this knowledge, Morgan and his students began the first chromosomal map of the fruit fly Drosophila. In 1928, Frederick Griffith showed that genes could be transferred. In what is now known as Griffith's experiment, injections into a mouse of a deadly strain of bacteria that had been heat-killed transferred genetic information to a safe strain of the same bacteria, killing the mouse.

In 1941, George Wells Beadle and Edward Lawrie Tatum showed that mutations in genes caused errors in certain steps in metabolic pathways. This showed that specific genes code for specific proteins, leading to the "one gene, one enzyme" hypothesis. Oswald Avery, Collin Macleod, and Maclyn McCarty showed in 1944 that DNA holds the gene's information. In 1953, James D. Watson and Francis Crick demonstrated the molecular structure of DNA. Together, these discoveries established the central dogma of molecular biology, which states that proteins are translated from RNA which is transcribed from DNA. This dogma has since been shown to have exceptions, such as reverse transcription in retroviruses.

Richard Roberts and Phillip Sarp discovered in 1977 that genes can be split into segments. This leads to the idea that one gene can make several proteins. Recently (as of 2003-2006), biological results let the notion of gene appear more slippery. In particular, genes do not seem to sit side by side on DNA like discrete beads. Instead, regions of the DNA producing distinct proteins may overlap, so that the idea emerges that "genes are one long continuum". (Pearson, 2006)

Evolutionary concept of gene

George C. Williams first explicitly advocated the gene-centric view of evolution in his book Adaptation and Natural Selection. Also, he proposed an evolutionary concept of gene to be used when we are talking about natural selection favoring some gene. The definition is: "that which segregates and recombines with appreciable frequency." According to this definition, even an asexual genome could be considered a gene, insofar it have an appreciable permanency through many generations.

The difference is: the molecular gene transcribes as a unit, and the evolutionary gene inherits as a unit.

Richard Dawkins' The Selfish Gene and The Extended Phenotype defended the idea that the gene is the only replicator in living systems. This means that only genes transmit their structure largely intact and are potentially immortal in the form of copies. So, genes should be the unit of selection. In River Out of Eden, Dawkins further refined the idea of gene-centric selection by describing life as a river of compatible genes flowing through geological time. Scoop up a bucket of genes from the river of genes, and we have an organism serving as temporary bodies. A river of genes may fork into two branches representing two non-interbreeding species as a result of geographical separation.