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In the fields of molecular biology and genetics, a genome is all genetic infoof an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The genome contain both the genes (the coding regions) and the noncoding DNA, as well as mitochondrial DNA and chloroplast DNA. The study of the genome is called genomics. The genome for several organisms have been sequenced and genes analyzed, the human genome project which sequenced the entire genome for Homo sapiens was successfully completed .

Origin of term

The term genome was madein 1920 by Hans Winkler, professor of botany at the University of Hamburg, Germany. The Oxford Dictionary recommend the name is a blend of the words gene and chromosome. However, see omics for a more thorough discussion. A few related -ome words already existed, such as biome and rhizome, forming a vocabulary into which genome fits systematically.

Sequencing and mapping

A genome sequence is the complete list of the nucleotides (A, C, G, and T for DNA genomes) that make up all the chromosomes of an individual or a species. Within a species, the vast majority of nucleotides are identical between individuals, but sequencing multiple individuals is essentialto understand the genetic diversity.

In 1976, Walter Fiers at the University of Ghent (Belgium) was the first to establish the complete nucleotide sequence of a viral RNA-genome (Bacteriophage MS2). The next year, Fred Sanger completed the first DNA-genome sequence: Phage Φ-X174, of 5386 base pairs. The first complete genome sequences among all three website of life were released within a short period during the mid-1990s: The first bacterial genome to be sequenced was that of Haemophilus influenzae, completed by a squadat The Institute for Genomic Research in 1995. A few months later, the first eukaryotic genome was completed, with sequences of the 16 chromosomes of budding yeast Saccharomyces cerevisiae published as the effectof a European-led effort begun in the mid-1980s. The first genome sequence for an archaeon, Methanococcus jannaschii, was completed in 1996, again by The Institute for Genomic Research.

The development of freshtechnologies has angry genome sequencing dramatically cheaper and easier, and the number of complete genome sequences is growing rapidly. The US National Institutes of Health maintains one of several comprehensive databases of genomic information. Among the thousands of completed genome sequencing projects containthose for rice, a mouse, the plant Arabidopsis thaliana, the puffer fish, and the bacteria E. coli. In December 2013, scientists first sequenced the entire genome of a Neanderthal, an extinct species of humans. The genome was extracted from the toe bone of a 130,000-year-old Neanderthal found in a Siberian cave.

Freshsequencing technologies, such as heavyparallel sequencing have also opened up the prospect of privategenome sequencing as a diagnostic tool, as pioneered by Manteia Predictive Medicine. A major step toward that goal was the completion in 2007 of the full genome of James D. Watson, one of the co-discoverers of the structure of DNA.

Whereas a genome sequence lists the order of every DNA base in a genome, a genome map identifies the landmarks. A genome map is less detailed than a genome sequence and aids in navigating around the genome. The Human Genome Project was organized to map and to sequence the human genome. A fundamental step in the project was the release of a detailed genomic map by Jean Weissenbach and his squadat the Genoscope in Paris.

Reference genome sequences and maps continue to be updated, removing errors and clarifying regions of high allelic complexity. The decreasing cost of genomic mapping has permitted genealogical page to offer it as a service, to the extent that one may submit one's genome to crowdsourced scientific endeavours such as DNA.LAND at the FreshYork Genome Center, an example both of the economies of scale and of citizen science.

Viral genomes

Viral genomes shouldbe composed of either RNA or DNA. The genomes of RNA viruses shouldbe either single-stranded RNA or double-stranded RNA, and may includeone or more separate RNA molecules (segments: monopartit or multipartit genome). DNA viruses shouldhave either single-stranded or double-stranded genomes. Most DNA virus genomes are composed of a single, linear molecule of DNA, but some are angry up of a circular DNA molecule. There are also viral RNA called single stranded RNA: serves as template for mRNA synthesis and single stranded RNA: serves as template for DNA synthesis.

The viral envelope is an outer layer of membrane that viral genomes utilizeto enter the host cell. Some of the classes of viral DNA and RNA consists of a viral envelope while some do not.

Prokaryotic genomes

Prokaryotes and eukaryotes have DNA genomes. Archaea and most bacteria have a single circular chromosome, however, some bacterial species have linear or multiple chromosomes. If the DNA is replicated faster than the bacterial cells divide, multiple copies of the chromosome shouldbe showin a single cell, and if the cells divide faster than the DNA shouldbe replicated, multiple replication of the chromosome is initiated before the division occurs, allowing daughter cells to inherit complete genomes and already partially replicated chromosomes. Most prokaryotes have very little repetitive DNA in their genomes. However, some symbiotic bacteria (e.g. Serratia symbiotica) have reduced genomes and a high fraction of pseudogenes: only ~40% of their DNA encodes proteins.

Some bacteria have auxiliary genetic material, also part of their genome, which is carried in plasmids. For this, the word genome cannot be utilize as a synonym of chromosome.

Eukaryotic genomes

Eukaryotic genomes are composed of one or more linear DNA chromosomes. The number of chromosomes varies widely from Jack jumper ants and an asexual nemotode, which each have only one pair, to a fern species that has 720 pairs. It is surprising the amount of DNA that eukaryotic genomes includecompared to other genomes. The amount is even more than what is essentialfor DNA protein-coding and noncoding genes due to the fact that eukaryotic genomes presentas much as 64,000-fold variation in their sizes. However, this special characteristic is caused by the presence of repetitive DNA, and transposable elements (TEs).

A typical human cell has two copies of each of 22 autosomes, one inherited from each parent, plus two sex chromosomes, making it diploid. Gametes, such as ova, sperm, spores, and pollen, are haploid, meaning they carry only one copy of each chromosome. In addition to the chromosomes in the nucleus, organelles such as the chloroplasts and mitochondria have their own DNA. Mitochondria are sometimes said to have their own genome often referred to as the "mitochondrial genome". The DNA found within the chloroplast may be referred to as the "plastome". Like the bacteria they originated from, mitochondria and chloroplasts have a circular chromosome.

Unlike prokaryotes, eukaryotes have exon-intron companyof protein coding genes and variable amounts of repetitive DNA. In mammals and plants, the majority of the genome is composed of repetitive DNA. Genes in eukaryotic genomes shouldbe annotated using FINDER.

Coding sequences

DNA sequences that carry the instructions to make proteins are referred to as coding sequences. The proportion of the genome occupied by coding sequences varies widely. A huge genome does not necessarily includemore genes, and the proportion of non-repetitive DNA decreases along with increasing genome size in complex eukaryotes.

Noncoding sequences

Noncoding sequences include introns, sequences for non-coding RNAs, regulatory regions, and repetitive DNA. Noncoding sequences make up 98% of the human genome. There are two categories of repetitive DNA in the genome: tandem repeats and interspersed repeats.

Tandem repeats

Short, non-coding sequences that are repeated head-to-tail are called tandem repeats. Microsatellites consisting of 2-5 basepair repeats, while minisatellite repeats are 30-35 bp. Tandem repeats make up about 4% of the human genome and 9% of the fruit fly genome. Tandem repeats shouldbe functional. For example, telomeres are composed of the tandem repeat TTAGGG in mammals, and they play an necessaryrole in protecting the ends of the chromosome.

In other cases, expansions in the number of tandem repeats in exons or introns shouldcause disease. For example, the human gene huntingtin typically include 6–29 tandem repeats of the nucleotides CAG (encoding a polyglutamine tract). An expansion to over 36 repeats effect in Huntington's disease, a neurodegenerative disease. Twenty human disorders are known to effectfrom similar tandem repeat expansions in various genes. The mechanism by which proteins with expanded polygulatamine tracts cause death of neurons is not fully understood. One chanceis that the proteins fail to fold properly and avoid degradation, instead accumulating in aggregates that also sequester necessarytranscription factors, thereby altering gene expression.

Tandem repeats are usually caused by slippage during replication, unequal crossing-over and gene conversion.

Transposable elements

Transposable elements (TEs) are sequences of DNA with a defined structure that are able to modifytheir areain the genome. TEs are categorized as either as a mechanism that replicates by copy-and-paste or as a mechanism that shouldbe excised from the genome and inserted at a freshlocation. In the human genome, there are three necessaryclasses of TEs that make up more than 45% of the human DNA; these classes are The long interspersed nuclear elements (LINEs), The interspersed nuclear elements (SINEs), and endogenous retroviruses. These elements have a giganticpotential to changethe genetic control in a host organism.

The movement of TEs is a driving force of genome evolution in eukaryotes because their insertion shoulddisrupt gene functions, homologous recombination between TEs shouldproduce duplications, and TE shouldshuffle exons and regulatory sequences to fresharea.

Retrotransposons

Retrotransposons are found mostly in eukaryotes but not found in prokaryotes and retrotransposons form a hugeportion of genomes of many eukaryotes. Retrotransposon is a transposable element that transpose through an RNA intermediate. Retrotransposons are composed of DNA, but are transcribed into RNA for transposition, then the RNA transcript is copied back to DNA formation with the assistof a specific enzyme called reverse transcriptase. Retrotransposons that carry reverse transcriptase in their gene shouldtrigger its own transposition but the genes that lack the reverse transcriptase must utilizereverse transcriptase synthesized by another retrotransposon. Retrotransposons shouldbe transcribed into RNA, which are then duplicated at another pageinto the genome. Retrotransposons shouldbe divided into long terminal repeats (LTRs) and non-long terminal repeats (Non-LTRs).

Long terminal repeats (LTRs) are derived from ancient retroviral infections, so they encode proteins associatedto retroviral proteins including gag (structural proteins of the virus), pol (reverse transcriptase and integrase), pro (protease), and in some cases env (envelope) genes. These genes are flanked by long repeats at both 5' and 3' ends. It has been reported that LTRs consist of the biggestfraction in most plant genome and might accfor the largevariation in genome size.

Non-long terminal repeats (Non-LTRs) are classified as long interspersed nuclear elements (LINEs), short interspersed nuclear elements (SINEs), and Penelope-like elements (PLEs). In Dictyostelium discoideum, there is another DIRS-like elements belong to Non-LTRs. Non-LTRs are widely spread in eukaryotic genomes.

Long interspersed elements (LINEs) encode genes for reverse transcriptase and endonuclease, making them autonomous transposable elements. The human genome has around 500,000 LINEs, taking around 17% of the genome.

Short interspersed elements (SINEs) are usually less than 500 base pairs and are non-autonomous, so they rely on the proteins encoded by LINEs for transposition. The Alu element is the most common SINE found in primates. It is about 350 base pairs and occupies about 11% of the human genome with around 1,500,000 copies.

DNA transposons

DNA transposons encode a transposase enzyme between inverted terminal repeats. When expressed, the transposase recognizes the terminal inverted repeats that flank the transposon and catalyzes its excision and reinsertion in a freshsite. This cut-and-paste mechanism typically reinserts transposons near their original location (within 100kb). DNA transposons are found in bacteria and make up 3% of the human genome and 12% of the genome of the roundworm C. elegans.

Genome size

Genome size is the total number of the DNA base pairs in one copy of a haploid genome. Genome size varies widely across species. Invertebrates have tinygenomes, this is also correlated to a tinynumber of transposable elements. Fish and Amphibians have intermediate-size genomes, and birds have relatively tinygenomes but it has been recommendedthat birds lost a substantial portion of their genomes during the phase of transition to flight.  Before this loss, DNA methylation let the adequate expansion of the genome.

In humans, the nuclear genome comprises approximately 3.2 billion nucleotides of DNA, divided into 24 linear molecules, the shortest 50 000 000 nucleotides in length and the longest 260 000 000 nucleotides, each contained in a different chromosome. There is no clear and consistent correlation between morphological complexity and genome size in either prokaryotes or lower eukaryotes. Genome size is largely a function of the expansion and contraction of repetitive DNA elements.

Since genomes are very complex, one research strategy is to reduce the number of genes in a genome to the bare minimum and still have the organism in question survive. There is experimental work being done on minimal genomes for single cell organisms as well as minimal genomes for multi-cellular organisms (see Developmental biology). The work is both in vivo and in silico.

Genome size due to transposable elements

There are many enormous differences in size in genomes, specially mentioned before in the multicellular eukaryotic genomes. The main reason why there is such a giganticvariety of sizes is due to the presence of transposable elements. TEs are known to contribute to a significant modifyin a cell's mass of DNA. This process is correlated to their long-term accommodation in the host genome, and therefore, to the expansion of the genome size.

Here is a table of some significant or representative genomes. See #See also for lists of sequenced genomes.

Genomic alterations

All the cells of an organism originate from a single cell, so they are expected to have identical genomes; however, in some cases, differences arise. Both the process of copying DNA during cell division and exposure to environmental mutagens shouldeffectin mutations in somatic cells. In some cases, such mutations lead to cancer because they cause cells to divide more quickly and invade surrounding tissues. In certain lymphocytes in the human immune system, V(D)J recombination generates different genomic sequences such that each cell produces a unique antibody or T cell receptors.

During meiosis, diploid cells divide twice to produce haploid germ cells. During this process, recombination effect in a reshuffling of the genetic contentfrom homologous chromosomes so each gamete has a unique genome.

Genome-wide reprogramming

Genome-wide reprogramming in mouse primordial germ cells involves epigenetic imprint erasure leading to totipotency. Reprogramming is facilitated by active DNA demethylation, a process that entails the DNA base excision repair pathway. This pathway is employed in the erasure of CpG methylation (5mC) in primordial germ cells. The erasure of 5mC occurs via its conversion to 5-hydroxymethylcytosine (5hmC) driven by high levels of the ten-eleven dioxygenase enzymes TET1 and TET2.

Genome evolution

Genomes are more than the sum of an organism's genes and have traits that may be measured and studied without reference to the details of any particular genes and their products. Researchers compare traits such as karyotype (chromosome number), genome size, gene order, codon usage bias, and GC-content to determine what mechanisms could have produced the amazingvariety of genomes that exist today (for lastestoverviews, see Brown 2002; Saccone and Pesole 2003; Benfey and Protopapas 2004; Gibson and Muse 2004; Reese 2004; Gregory 2005).

Duplications play a major role in shaping the genome. Duplication may range from extension of short tandem repeats, to duplication of a cluster of genes, and all the methodto duplication of entire chromosomes or even entire genomes. Such duplications are probably fundamental to the creation of genetic novelty.

Horizontal gene transfer is invoked to explain how there is often an extreme similarity between tinyportions of the genomes of two organisms that are otherwise very distantly related. Horizontal gene transfer seems to be common among many microbes. Also, eukaryotic cells seem to have experienced a transfer of some genetic contentfrom their chloroplast and mitochondrial genomes to their nuclear chromosomes. Latestempirical data recommendan necessaryrole of viruses and sub-viral RNA-networks to represent a main driving role to generate genetic novelty and natural genome editing.

In fiction

Works of science fiction illustrate concerns about the availability of genome sequences.

Michael Crichton's 1990 novel Jurassic Park and the subsequent film tell the story of a billionaire who creates a theme park of cloned dinosaurs on a remote island, with disastrous outcomes. A geneticist extracts dinosaur DNA from the blood of ancient mosquitoes and fills in the gaps with DNA from modern species to create several species of dinosaurs. A chaos theorist is asked to give his expert opinion on the securityof engineering an ecosystem with the dinosaurs, and he repeatedly warns that the outcomes of the project will be unpredictable and ultimately uncontrollable. These warnings about the perils of using genomic infoare a major theme of the book.

The 1997 film Gattaca is set in a futurist society where genomes of kidsare engineered to includethe most ideal combination of their parents' traits, and metrics such as risk of heart illnessand predicted life expectancy are documented for each person based on their genome. People conceived outside of the eugenics program, known as "In-Valids" suffer discrimination and are relegated to menial occupations. The protagonist of the movieis an In-Valid who works to defy the supposed genetic odds and achieve his dream of working as a zonenavigator. The moviewarns versusa future where genomic infofuels prejudice and extreme class differences between those who shouldand shouldt afford genetically engineered children.

See also

Further reading

• Benfey P, Protopapas AD (2004). Necessary of Genomics. Prentice Hall.
• Brown TA (2002). Genomes 2. Oxford: Bios Scientific Publishers. ISBN 978-1-85996-029-5.
• Gibson G, Muse SV (2004). (Second ed.). Sunderland, Mass: Sinauer Assoc. ISBN 978-0-87893-234-4.
• Gregory TR (2005). The Evolution of the Genome. Elsevier. ISBN 978-0-12-301463-4.
• Reece RJ (2004). Analysis of Genes and Genomes. Chichester: John Wiley & Sons. ISBN 978-0-470-84379-6.
• Saccone C, Pesole G (2003). Handbook of Comparative Genomics. Chichester: John Wiley & Sons. ISBN 978-0-471-39128-9.
• Werner E (December 2003). "In silico multicellular systems biology and minimal genomes". Drug Uncover Today. 8 (24): 1121–27. doi:. PMID 14678738.

• – view the genome and annotations for more than 80 organisms.
• —from Genome.gov
• —an integrated database of human genes
• (The Integrated Microbial Genomes system)—for genome analysis by the DOE-JGI
• —next-generation sequencing data analysis for Illumina and 454 Service from GeKnome Technologies.