This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA
and to a chromosome
are regions often found in eukaryote
genes which are removed in the splicing
process: only the exons
encode the protein
. This diagram labels a region of only 40 or so bases as a gene. In reality many genes are much larger.
Genes are material entities that parents pass to offspring during reproduction. These entities encode information essential for the construction and regulation of polypeptides, proteins and other molecules that determine the growth and functioning of the organism.
The word "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 material entity that supports the gene in one discipline is not the same as in the other.
Following the discovery that DNA is the genetic material, and with 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. In the molecular-biological sense, genes are the segments of DNA which cells transcribe into RNA and translate, at least in part, into proteins.
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: 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 "multifactoral") traits. The term phenotype refers to the characteristics that result from this interplay (see genotype-phenotype distinction).
Properties of genes
In molecular biology, the DNA of a gene encodes the chemical structure of a protein. The genetic code determines the sequence of the amino acids that make up a protein. The coding of a three nucleotide DNA sequence to a specific amino acid 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 behaviors. 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 color. A gene's most common allele is called the wild type allele, and rare alleles are called mutants.
Normally, RNA is an intermediate product in the translation of a molecular gene into a protein. However, for some gene sequences, RNA molecules are actually the functional end products. For example, RNAs known as ribozymes are capable of enzymatic function, or 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.
All 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 AIDS, 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 Genew (http://www.gene.ucl.ac.uk/cgi-bin/nomenclature/searchgenes.pl), the Human Gene Nomenclature 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 also be used in other species, especially the mouse.
Typical numbers of genes in an organism
The following 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 it is only possible to discover a gene, and no techniques currently exist to prove that a DNA sequence contains no gene. Nonetheless, estimates are made based on current knowledge.
|organism ||genes ||base pairs |
|Plant ||<50,000 ||<1011 |
|Human ||25,000 ||3×109 |
|Fly ||12,000 ||1.6×108 |
|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 |
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 genes themselves. 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 2 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. So, 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. So, 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).
The existence of genes was first suggested by Gregor Mendel, who 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 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 a 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 transcribed from RNA which is translated from DNA. This dogma has since been shown to have exceptions, such as reverse transcription in retroviruses.
- Genetics, Gene expression, Gene therapy, Homeobox, Human Genome Project, Genomics, DNA, Protein, Gene family
- Genetic programming, Genetic algorithm
- Meme, Memetics
- Human Genome Organisation, HUGO (http://www.gene.ucl.ac.uk/hugo/)
- HUGO Gene Nomenclature Committee, HGNC (http://www.gene.ucl.ac.uk/nomenclature)
- Genew the Human Gene Nomenclature Database (http://www.gene.ucl.ac.uk/cgi-bin/nomenclature/searchgenes.pl)
- Recount slashes number of human genes (http://www.newscientist.com/news/news.jsp?id=ns99996561) (from New Scientist magazine)
- National Human Genome Research Institute - News Release (http://www.genome.gov/12513430)
- Nature - 21 October 2004 - Finishing the euchromatic sequence of the human genome (http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v431/n7011/full/nature03001_fs.html)