Genomics is an interdisciplinary field of
biology
Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent field. For instance, all organisms are made up of cells that process hereditary i ...
focusing on the structure, function, evolution, mapping, and editing of
genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
s. A genome is an organism's complete set of
DNA, including all of its genes as well as its hierarchical, three-dimensional structural configuration.
In contrast to
genetics
Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar wor ...
, which refers to the study of ''individual'' genes and their roles in inheritance, genomics aims at the collective characterization and quantification of ''all'' of an organism's genes, their interrelations and influence on the organism.
Genes may direct the production of
proteins
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
with the assistance of enzymes and messenger molecules. In turn, proteins make up body structures such as organs and tissues as well as control chemical reactions and carry signals between cells. Genomics also involves the sequencing and analysis of genomes through uses of high throughput
DNA sequencing
DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, guanine, cytosine, and thymine. Th ...
and
bioinformatics
Bioinformatics () is an interdisciplinary field that develops methods and software tools for understanding biological data, in particular when the data sets are large and complex. As an interdisciplinary field of science, bioinformatics combi ...
to assemble and analyze the function and structure of entire genomes.
Advances in genomics have triggered a revolution in discovery-based research and
systems biology
Systems biology is the computational modeling, computational and mathematical analysis and modeling of complex biological systems. It is a biology-based interdisciplinary field of study that focuses on complex interactions within biological syst ...
to facilitate understanding of even the most complex biological systems such as the brain.
The field also includes studies of intragenomic (within the genome) phenomena such as
epistasis
Epistasis is a phenomenon in genetics in which the effect of a gene mutation is dependent on the presence or absence of mutations in one or more other genes, respectively termed modifier genes. In other words, the effect of the mutation is dep ...
(effect of one gene on another),
pleiotropy
Pleiotropy (from Greek , 'more', and , 'way') occurs when one gene influences two or more seemingly unrelated phenotypic traits. Such a gene that exhibits multiple phenotypic expression is called a pleiotropic gene. Mutation in a pleiotropic g ...
(one gene affecting more than one trait),
heterosis
Heterosis, hybrid vigor, or outbreeding enhancement is the improved or increased function of any biological quality in a hybrid offspring. An offspring is heterotic if its traits are enhanced as a result of mixing the genetic contributions of ...
(hybrid vigour), and other interactions between
loci and
allele
An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution.
::"The chro ...
s within the genome.
History
Etymology
From the Greek ΓΕΝ
''gen'', "gene" (gamma, epsilon, nu, epsilon) meaning "become, create, creation, birth", and subsequent variants: genealogy, genesis, genetics, genic, genomere, genotype, genus etc. While the word ''genome'' (from the
German
German(s) may refer to:
* Germany (of or related to)
**Germania (historical use)
* Germans, citizens of Germany, people of German ancestry, or native speakers of the German language
** For citizens of Germany, see also German nationality law
**Ger ...
''Genom'', attributed to
Hans Winkler
Hans Karl Albert Winkler (23 April 1877 – 22 November 1945) was a German botanist. He was Professor of Botany at the University of Hamburg, and a director of that university's Institute of Botany. Winkler coined the term 'heteroploidy' in 191 ...
) was in use in
English
English usually refers to:
* English language
* English people
English may also refer to:
Peoples, culture, and language
* ''English'', an adjective for something of, from, or related to England
** English national ide ...
as early as 1926,
the term ''genomics'' was coined by Tom Roderick, a
geneticist
A geneticist is a biologist or physician who studies genetics, the science of genes, heredity, and variation of organisms. A geneticist can be employed as a scientist or a lecturer. Geneticists may perform general research on genetic processe ...
at the
Jackson Laboratory
The Jackson Laboratory (often abbreviated as JAX) is an independent, non-profit biomedical research institution which was founded by a eugenicist. It employs more than 3,000 employees in Bar Harbor, Maine; Sacramento, California; Farmington, Con ...
(
Bar Harbor, Maine
Bar Harbor is a resort town on Mount Desert Island in Hancock County, Maine, United States. As of the 2020 census, its population is 5,089. During the summer and fall seasons, it is a popular tourist destination and, until a catastrophic fire i ...
), over beers with Jim Womack, Tom Shows and
Stephen O’Brien at a meeting held in
Maryland
Maryland ( ) is a state in the Mid-Atlantic region of the United States. It shares borders with Virginia, West Virginia, and the District of Columbia to its south and west; Pennsylvania to its north; and Delaware and the Atlantic Ocean to ...
on the mapping of the human genome in 1986.
First as the name for a
new journal and then as a whole new science discipline.
Early sequencing efforts
Following
Rosalind Franklin
Rosalind Elsie Franklin (25 July 192016 April 1958) was a British chemist and X-ray crystallographer whose work was central to the understanding of the molecular structures of DNA (deoxyribonucleic acid), RNA (ribonucleic acid), viruses, co ...
's confirmation of the helical structure of DNA,
James D. Watson
James Dewey Watson (born April 6, 1928) is an American molecular biologist, geneticist, and zoologist. In 1953, he co-authored with Francis Crick the academic paper proposing the double helix structure of the DNA molecule. Watson, Crick and ...
and
Francis Crick
Francis Harry Compton Crick (8 June 1916 – 28 July 2004) was an English molecular biologist, biophysicist, and neuroscientist. He, James Watson, Rosalind Franklin, and Maurice Wilkins played crucial roles in deciphering the helical struc ...
's publication of the structure of DNA in 1953 and
Fred Sanger
Frederick Sanger (; 13 August 1918 – 19 November 2013) was an English biochemist who received the Nobel Prize in Chemistry twice.
He won the 1958 Chemistry Prize for determining the amino acid sequence of insulin and numerous other ...
's publication of the
Amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
sequence of insulin in 1955, nucleic acid sequencing became a major target of early
molecular biologists
Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
.
In 1964,
Robert W. Holley
Robert William Holley (January 28, 1922 – February 11, 1993) was an American biochemist. He shared the Nobel Prize in Physiology or Medicine in 1968 (with Har Gobind Khorana and Marshall Warren Nirenberg) for describing the structure of alani ...
and colleagues published the first nucleic acid sequence ever determined, the
ribonucleotide
In biochemistry, a ribonucleotide is a nucleotide containing ribose as its pentose component. It is considered a molecular precursor of nucleic acids. Nucleotides are the basic building blocks of DNA and RNA. Ribonucleotides themselves are basic m ...
sequence of
alanine
Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group side c ...
transfer RNA
Transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes), that serves as the physical link between the mRNA and the amino ac ...
.
Extending this work,
Marshall Nirenberg
Marshall Warren Nirenberg (April 10, 1927 – January 15, 2010) was an American biochemist and geneticist. He shared a Nobel Prize in Physiology or Medicine in 1968 with Har Gobind Khorana and Robert W. Holley for "breaking the genetic code" and ...
and
Philip Leder
Philip Leder (November 19, 1934 – February 2, 2020) was an American geneticist.
Early life and education
Leder was born in Washington, D.C. and studied at Harvard University, graduating in 1956. In 1960, he graduated from Harvard Medical Sch ...
revealed the triplet nature of the
genetic code
The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...
and were able to determine the sequences of 54 out of 64
codons
The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...
in their experiments.
In 1972,
Walter Fiers
Walter Fiers (31 January 1931 in Ypres, West Flanders – 28 July 2019 in Destelbergen) was a Belgian molecular biologist.
He obtained a degree of Engineer for Chemistry and Agricultural Industries at the University of Ghent in 1954, and started ...
and his team at the Laboratory of Molecular Biology of the
University of Ghent
Ghent University ( nl, Universiteit Gent, abbreviated as UGent) is a public research university located in Ghent, Belgium.
Established before the state of Belgium itself, the university was founded by the Dutch King William I in 1817, when the ...
(
Ghent
Ghent ( nl, Gent ; french: Gand ; traditional English: Gaunt) is a city and a municipality in the Flemish Region of Belgium. It is the capital and largest city of the East Flanders province, and the third largest in the country, exceeded in ...
,
Belgium
Belgium, ; french: Belgique ; german: Belgien officially the Kingdom of Belgium, is a country in Northwestern Europe. The country is bordered by the Netherlands to the north, Germany to the east, Luxembourg to the southeast, France to th ...
) were the first to determine the sequence of a gene: the gene for
Bacteriophage MS2
Bacteriophage MS2 (''Emesvirus zinderi''), commonly called MS2, is an icosahedral, positive-sense single-stranded RNA virus that infects the bacterium ''Escherichia coli'' and other members of the Enterobacteriaceae. MS2 is a member of a family ...
coat protein.
Fiers' group expanded on their MS2 coat protein work, determining the complete nucleotide-sequence of bacteriophage MS2-RNA (whose genome encodes just four genes in 3569
base pair
A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
s [bp]) and
Simian virus 40
SV40 is an abbreviation for simian vacuolating virus 40 or simian virus 40, a polyomavirus that is found in both monkeys and humans. Like other polyomaviruses, SV40 is a DNA virus that has the potential to cause tumors in animals, but most often ...
in 1976 and 1978, respectively.
DNA-sequencing technology developed
In addition to his seminal work on the amino acid sequence of insulin,
Frederick Sanger
Frederick Sanger (; 13 August 1918 – 19 November 2013) was an English biochemist who received the Nobel Prize in Chemistry twice.
He won the 1958 Chemistry Prize for determining the amino acid sequence of insulin and numerous other p ...
and his colleagues played a key role in the development of DNA sequencing techniques that enabled the establishment of comprehensive genome sequencing projects.
In 1975, he and Alan Coulson published a sequencing procedure using DNA polymerase with radiolabelled nucleotides that he called the ''Plus and Minus technique''.
This involved two closely related methods that generated short oligonucleotides with defined 3' termini. These could be fractionated by
electrophoresis
Electrophoresis, from Ancient Greek ἤλεκτρον (ḗlektron, "amber") and φόρησις (phórēsis, "the act of bearing"), is the motion of dispersed particles relative to a fluid under the influence of a spatially uniform electric fie ...
on a
polyacrylamide
Polyacrylamide (abbreviated as PAM) is a polymer with the formula (-CH2CHCONH2-). It has a linear-chain structure. PAM is highly water-absorbent, forming a soft gel when hydrated. In 2008, an estimated 750,000,000 kg were produced, mainly fo ...
gel (called polyacrylamide gel electrophoresis) and visualised using autoradiography. The procedure could sequence up to 80 nucleotides in one go and was a big improvement, but was still very laborious. Nevertheless, in 1977 his group was able to sequence most of the 5,386 nucleotides of the single-stranded
bacteriophage
A bacteriophage (), also known informally as a ''phage'' (), is a duplodnaviria virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν ('), meaning "to devour". Bacteri ...
φX174, completing the first fully sequenced DNA-based genome.
The refinement of the ''Plus and Minus'' method resulted in the chain-termination, or
Sanger method (see
below
Below may refer to:
*Earth
*Ground (disambiguation)
*Soil
*Floor
*Bottom (disambiguation)
Bottom may refer to:
Anatomy and sex
* Bottom (BDSM), the partner in a BDSM who takes the passive, receiving, or obedient role, to that of the top or ...
), which formed the basis of the techniques of DNA sequencing, genome mapping, data storage, and bioinformatic analysis most widely used in the following quarter-century of research.
In the same year
Walter Gilbert
Walter Gilbert (born March 21, 1932) is an American biochemist, physicist, molecular biology pioneer, and Nobel laureate.
Education and early life
Walter Gilbert was born in Boston, Massachusetts, on March 21, 1932, the son of Emma (Cohen), a ...
and
Allan Maxam
Allan Maxam (born October 28, 1942) is one of the pioneers of molecular genetics. He was one of the contributors to develop a DNA sequencing method at Harvard University, while working as a student in the laboratory of Walter Gilbert.
Walter Gi ...
of
Harvard University
Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of higher le ...
independently developed the
Maxam-Gilbert method (also known as the ''chemical method'') of DNA sequencing, involving the preferential cleavage of DNA at known bases, a less efficient method.
For their groundbreaking work in the sequencing of nucleic acids, Gilbert and Sanger shared half the 1980
Nobel Prize
The Nobel Prizes ( ; sv, Nobelpriset ; no, Nobelprisen ) are five separate prizes that, according to Alfred Nobel's will of 1895, are awarded to "those who, during the preceding year, have conferred the greatest benefit to humankind." Alfr ...
in chemistry with
Paul Berg
Paul Berg (born June 30, 1926) is an American biochemist and professor emeritus at Stanford University. He was the recipient of the Nobel Prize in Chemistry in 1980, along with Walter Gilbert and Frederick Sanger. The award recognized their con ...
(
recombinant DNA
Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be foun ...
).
Complete genomes
The advent of these technologies resulted in a rapid intensification in the scope and speed of completion of
genome sequencing projects. The first complete genome sequence of a
eukaryotic organelle, the human
mitochondrion
A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...
(16,568 bp, about 16.6 kb [kilobase]), was reported in 1981,
and the first
chloroplast
A chloroplast () is a type of membrane-bound organelle known as a plastid that conducts photosynthesis mostly in plant and algal cells. The photosynthetic pigment chlorophyll captures the energy from sunlight, converts it, and stores it in ...
genomes followed in 1986.
In 1992, the first eukaryotic
chromosome
A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
, chromosome III of brewer's yeast ''
Saccharomyces cerevisiae
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been o ...
'' (315 kb) was sequenced.
The first free-living organism to be sequenced was that of ''
Haemophilus influenzae
''Haemophilus influenzae'' (formerly called Pfeiffer's bacillus or ''Bacillus influenzae'') is a Gram-negative, non-motile, coccobacillary, facultatively anaerobic, capnophilic pathogenic bacterium of the family Pasteurellaceae. The bacteria ...
'' (1.8 Mb [megabase]) in 1995.
The following year a consortium of researchers from laboratories across
North America
North America is a continent in the Northern Hemisphere and almost entirely within the Western Hemisphere. It is bordered to the north by the Arctic Ocean, to the east by the Atlantic Ocean, to the southeast by South America and the Car ...
,
Europe
Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a Continent#Subcontinents, subcontinent of Eurasia ...
, and
Japan
Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the north ...
announced the completion of the first complete genome sequence of a eukaryote, ''
S. cerevisiae
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have bee ...
'' (12.1 Mb), and since then genomes have continued being sequenced at an exponentially growing pace.
, the complete sequences are available for: 2,719
virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsky's 1 ...
es, 1,115
archaea
Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebac ...
and
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
, and 36
eukaryote
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
s, of which about half are
fungi
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...
.
![Number of prokaryotic genomes and sequencing costs](https://upload.wikimedia.org/wikipedia/commons/7/73/Number_of_prokaryotic_genomes_and_sequencing_costs.svg)
Most of the microorganisms whose genomes have been completely sequenced are problematic
pathogen
In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
s, such as ''
Haemophilus influenzae
''Haemophilus influenzae'' (formerly called Pfeiffer's bacillus or ''Bacillus influenzae'') is a Gram-negative, non-motile, coccobacillary, facultatively anaerobic, capnophilic pathogenic bacterium of the family Pasteurellaceae. The bacteria ...
'', which has resulted in a pronounced bias in their phylogenetic distribution compared to the breadth of microbial diversity.
Of the other sequenced species, most were chosen because they were well-studied model organisms or promised to become good models. Yeast (''
Saccharomyces cerevisiae
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been o ...
'') has long been an important
model organism
A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workin ...
for the
eukaryotic cell
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
, while the fruit fly ''
Drosophila melanogaster
''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly" or "pomace fly". Starting with Ch ...
'' has been a very important tool (notably in early pre-molecular
genetics
Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar wor ...
). The worm ''
Caenorhabditis elegans
''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (ro ...
'' is an often used simple model for
multicellular organism
A multicellular organism is an organism that consists of more than one cell, in contrast to unicellular organism.
All species of animals, land plants and most fungi are multicellular, as are many algae, whereas a few organisms are partially uni- ...
s. The zebrafish ''
Brachydanio rerio
The zebrafish (''Danio rerio'') is a freshwater fish belonging to the minnow family ( Cyprinidae) of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (and thus often ...
'' is used for many developmental studies on the molecular level, and the plant ''
Arabidopsis thaliana
''Arabidopsis thaliana'', the thale cress, mouse-ear cress or arabidopsis, is a small flowering plant native to Eurasia and Africa. ''A. thaliana'' is considered a weed; it is found along the shoulders of roads and in disturbed land.
A winter a ...
'' is a model organism for flowering plants. The
Japanese pufferfish
''Takifugu'' is a genus of pufferfish, often better known by the Japanese name . There are 25 species belonging to the genus ''Takifugu'' and most of these are native to salt and brackish waters of the northwest Pacific, but a few species are ...
(''
Takifugu rubripes
''Takifugu rubripes'', commonly known as the Japanese puffer, Tiger puffer, or torafugu ( ja, 虎河豚), is a pufferfish in the genus ''Takifugu''. It is distinguished by a very small genome that has been fully sequenced because of its use as a m ...
'') and the
spotted green pufferfish (''
Tetraodon nigroviridis
''Dichotomyctere nigroviridis'' ( syn. ''Tetraodon nigroviridis'') is one of the pufferfish known as the green spotted puffer. It is found across South and Southeast Asia in coastal freshwater,but survives the longest in brackish to saltwater, a ...
'') are interesting because of their small and compact genomes, which contain very little
noncoding DNA
Non-coding DNA (ncDNA) sequences are components of an organism's DNA that do not encode protein sequences. Some non-coding DNA is transcribed into functional non-coding RNA molecules (e.g. transfer RNA, microRNA, piRNA, ribosomal RNA, and regul ...
compared to most species.
The mammals dog (''
Canis familiaris
The dog (''Canis familiaris'' or ''Canis lupus familiaris'') is a domesticated descendant of the wolf. Also called the domestic dog, it is Domestication of the dog, derived from the extinct Pleistocene wolf, and the modern wolf is the dog's n ...
''),
brown rat (''
Rattus norvegicus
''Rattus'' is a genus of muroid rodents, all typically called rats. However, the term rat can also be applied to rodent species outside of this genus.
Species and description
The best-known ''Rattus'' species are the black rat (''R. rattus'') ...
''), mouse (''
Mus musculus
Mus or MUS may refer to:
Abbreviations
* MUS, the NATO country code for Mauritius
* MUS, the IATA airport code for Minami Torishima Airport
* MUS, abbreviation for the Centre for Modern Urban Studies on Campus The Hague, Leiden University, Neth ...
''), and chimpanzee (''
Pan troglodytes
The chimpanzee (''Pan troglodytes''), also known as simply the chimp, is a species of Hominidae, great ape native to the forest and savannah of tropical Africa. It has four confirmed subspecies and a fifth proposed subspecies. When its close r ...
'') are all important model animals in medical research.
A rough draft of the
human genome
The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the n ...
was completed by the
Human Genome Project
The Human Genome Project (HGP) was an international scientific research project with the goal of determining the base pairs that make up human DNA, and of identifying, mapping and sequencing all of the genes of the human genome from both a ...
in early 2001, creating much fanfare.
This project, completed in 2003, sequenced the entire genome for one specific person, and by 2007 this sequence was declared "finished" (less than one error in 20,000 bases and all chromosomes assembled).
In the years since then, the genomes of many other individuals have been sequenced, partly under the auspices of the
1000 Genomes Project
The 1000 Genomes Project (abbreviated as 1KGP), launched in January 2008, was an international research effort to establish by far the most detailed catalogue of human genetic variation. Scientists planned to sequence the genomes of at least one th ...
, which announced the sequencing of 1,092 genomes in October 2012.
Completion of this project was made possible by the development of dramatically more efficient sequencing technologies and required the commitment of significant
bioinformatics
Bioinformatics () is an interdisciplinary field that develops methods and software tools for understanding biological data, in particular when the data sets are large and complex. As an interdisciplinary field of science, bioinformatics combi ...
resources from a large international collaboration.
The continued analysis of human genomic data has profound political and social repercussions for human societies.
The "omics" revolution
The English-language
neologism
A neologism Greek νέο- ''néo''(="new") and λόγος /''lógos'' meaning "speech, utterance"] is a relatively recent or isolated term, word, or phrase that may be in the process of entering common use, but that has not been fully accepted int ...
omics informally refers to a field of study in biology ending in ''-omics'', such as genomics,
proteomics
Proteomics is the large-scale study of proteins. Proteins are vital parts of living organisms, with many functions such as the formation of structural fibers of muscle tissue, enzymatic digestion of food, or synthesis and replication of DNA. In ...
or
metabolomics
Metabolomics is the scientific study of chemical processes involving metabolites, the small molecule substrates, intermediates, and products of cell metabolism. Specifically, metabolomics is the "systematic study of the unique chemical fingerprin ...
. The related suffix -ome is used to address the objects of study of such fields, such as the
genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
,
proteome
The proteome is the entire set of proteins that is, or can be, expressed by a genome, cell, tissue, or organism at a certain time. It is the set of expressed proteins in a given type of cell or organism, at a given time, under defined conditions. ...
or
metabolome
The metabolome refers to the complete set of small-molecule chemicals found within a biological sample. The biological sample can be a cell, a cellular organelle, an organ, a tissue, a tissue extract, a biofluid or an entire organism. The smal ...
respectively. The suffix ''-ome'' as used in molecular biology refers to a ''totality'' of some sort; similarly omics has come to refer generally to the study of large, comprehensive biological data sets. While the growth in the use of the term has led some scientists (
Jonathan Eisen
Jonathan Andrew Eisen (born August 31, 1968) is an American evolutionary biologist, currently working at University of California, Davis. His academic research is in the fields of evolutionary biology, genomics and microbiology and he is the ac ...
, among others
) to claim that it has been oversold,
it reflects the change in orientation towards the quantitative analysis of complete or near-complete assortment of all the constituents of a system.
In the study of
symbioses
Symbiosis (from Greek , , "living together", from , , "together", and , bíōsis, "living") is any type of a close and long-term biological interaction between two different biological organisms, be it mutualistic, commensalistic, or parasit ...
, for example, researchers which were once limited to the study of a single gene product can now simultaneously compare the total complement of several types of biological molecules.
Genome analysis
After an organism has been selected, genome projects involve three components: the sequencing of DNA, the assembly of that sequence to create a representation of the original chromosome, and the annotation and analysis of that representation.
Sequencing
Historically, sequencing was done in ''sequencing centers'', centralized facilities (ranging from large independent institutions such as
Joint Genome Institute
The U.S. Department of Energy (DOE) Joint Genome Institute (JGI), first located in Walnut Creek then Berkeley, California, was created in 1997 to unite the expertise and resources in genome mapping, DNA sequencing, technology development, and i ...
which sequence dozens of terabases a year, to local molecular biology core facilities) which contain research laboratories with the costly instrumentation and technical support necessary. As sequencing technology continues to improve, however, a new generation of effective fast turnaround benchtop sequencers has come within reach of the average academic laboratory.
On the whole, genome sequencing approaches fall into two broad categories, ''shotgun'' and ''high-throughput'' (or ''next-generation'') sequencing.
Shotgun sequencing
Shotgun sequencing is a sequencing method designed for analysis of DNA sequences longer than 1000 base pairs, up to and including entire chromosomes.
It is named by analogy with the rapidly expanding, quasi-random firing pattern of a
shotgun
A shotgun (also known as a scattergun, or historically as a fowling piece) is a long gun, long-barreled firearm designed to shoot a straight-walled cartridge (firearms), cartridge known as a shotshell, which usually discharges numerous small p ...
. Since gel electrophoresis sequencing can only be used for fairly short sequences (100 to 1000 base pairs), longer DNA sequences must be broken into random small segments which are then sequenced to obtain ''reads''. Multiple overlapping reads for the target DNA are obtained by performing several rounds of this fragmentation and sequencing. Computer programs then use the overlapping ends of different reads to assemble them into a continuous sequence.
Shotgun sequencing is a random sampling process, requiring over-sampling to ensure a given
nucleotide
Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules wi ...
is represented in the reconstructed sequence; the average number of reads by which a genome is over-sampled is referred to as
coverage
Coverage may refer to:
Filmmaking
* Coverage (lens), the size of the image a lens can produce
* Camera coverage, the amount of footage shot and different camera setups used in filming a scene
* Script coverage, a short summary of a script, wri ...
.
For much of its history, the technology underlying shotgun sequencing was the classical chain-termination method or '
Sanger method', which is based on the selective incorporation of chain-terminating
dideoxynucleotide
Dideoxynucleotides are chain-elongating inhibitors of DNA polymerase, used in the Sanger method for DNA sequencing. They are also known as 2',3' because both the 2' and 3' positions on the ribose lack hydroxyl groups, and are abbreviated as '' ...
s by
DNA polymerase
A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to create ...
during
in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...
DNA replication
In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inheritanc ...
.
Recently, shotgun sequencing has been supplanted by
high-throughput sequencing
DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, guanine, cytosine, and thymine. The ...
methods, especially for large-scale, automated
genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
analyses. However, the Sanger method remains in wide use, primarily for smaller-scale projects and for obtaining especially long contiguous DNA sequence reads (>500 nucleotides).
[ Chain-termination methods require a single-stranded DNA template, a DNA ]primer
Primer may refer to:
Arts, entertainment, and media Films
* ''Primer'' (film), a 2004 feature film written and directed by Shane Carruth
* ''Primer'' (video), a documentary about the funk band Living Colour
Literature
* Primer (textbook), a t ...
, a DNA polymerase
A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to create ...
, normal deoxynucleosidetriphosphates (dNTPs), and modified nucleotides (dideoxyNTPs) that terminate DNA strand elongation. These chain-terminating nucleotides lack a 3'- OH group required for the formation of a phosphodiester bond
In chemistry, a phosphodiester bond occurs when exactly two of the hydroxyl groups () in phosphoric acid react with hydroxyl groups on other molecules to form two ester bonds. The "bond" involves this linkage . Discussion of phosphodiesters is ...
between two nucleotides, causing DNA polymerase to cease extension of DNA when a ddNTP is incorporated. The ddNTPs may be radioactively or fluorescently labelled for detection in DNA sequencer
A DNA sequencer is a scientific instrument used to automate the DNA sequencing process. Given a sample of DNA, a DNA sequencer is used to determine the order of the four bases: G (guanine), C (cytosine), A (adenine) and T (thymine). This is the ...
s.[ Typically, these machines can sequence up to 96 DNA samples in a single batch (run) in up to 48 runs a day.]
High-throughput sequencing
The high demand for low-cost sequencing has driven the development of high-throughput sequencing technologies that parallelize the sequencing process, producing thousands or millions of sequences at once. High-throughput sequencing is intended to lower the cost of DNA sequencing beyond what is possible with standard dye-terminator methods. In ultra-high-throughput sequencing, as many as 500,000 sequencing-by-synthesis operations may be run in parallel.
The Illumina dye sequencing Illumina dye sequencing is a technique used to determine the series of base pairs in DNA, also known as DNA sequencing. The reversible terminated chemistry concept was invented by Bruno Canard and Simon Sarfati at the Pasteur Institute in Paris. I ...
method is based on reversible dye-terminators and was developed in 1996 at the Geneva Biomedical Research Institute, by Pascal Mayer
Pascal Mayer is a french scientist who was awarded Breakthrough Prize in Life Sciences in 2022 for researching paved way for inexpensive and rapid DNA sequencing
DNA sequencing is the process of determining the nucleic acid sequence – the o ...
and Laurent Farinelli. In this method, DNA molecules and primers are first attached on a slide and amplified with polymerase
A polymerase is an enzyme ( EC 2.7.7.6/7/19/48/49) that synthesizes long chains of polymers or nucleic acids. DNA polymerase and RNA polymerase are used to assemble DNA and RNA molecules, respectively, by copying a DNA template strand using base- ...
so that local clonal colonies, initially coined "DNA colonies", are formed. To determine the sequence, four types of reversible terminator bases (RT-bases) are added and non-incorporated nucleotides are washed away. Unlike pyrosequencing, the DNA chains are extended one nucleotide at a time and image acquisition can be performed at a delayed moment, allowing for very large arrays of DNA colonies to be captured by sequential images taken from a single camera. Decoupling the enzymatic reaction and the image capture allows for optimal throughput and theoretically unlimited sequencing capacity; with an optimal configuration, the ultimate throughput of the instrument depends only on the A/D conversion rate of the camera. The camera takes images of the fluorescently labeled nucleotides, then the dye along with the terminal 3' blocker is chemically removed from the DNA, allowing the next cycle.
An alternative approach, ion semiconductor sequencing Ion semiconductor sequencing is a method of DNA sequencing based on the detection of hydrogen ions that are released during the polymerization of DNA. This is a method of "sequencing by synthesis", during which a complementary strand is built based ...
, is based on standard DNA replication chemistry. This technology measures the release of a hydrogen ion each time a base is incorporated. A microwell containing template DNA is flooded with a single nucleotide
Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules wi ...
, if the nucleotide is complementary to the template strand it will be incorporated and a hydrogen ion will be released. This release triggers an ISFET
An ion-sensitive field-effect transistor (ISFET) is a field-effect transistor used for measuring ion concentrations in solution; when the ion concentration (such as H+, see pH scale) changes, the current through the transistor will change accord ...
ion sensor. If a homopolymer
A polymer (; Greek '' poly-'', "many" + '' -mer'', "part")
is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic an ...
is present in the template sequence multiple nucleotides will be incorporated in a single flood cycle, and the detected electrical signal will be proportionally higher.
Assembly
Sequence assembly
In bioinformatics, sequence assembly refers to aligning and merging fragments from a longer DNA sequence in order to reconstruct the original sequence. This is needed as DNA sequencing technology might not be able to 'read' whole genomes in one ...
refers to aligning and merging fragments of a much longer DNA sequence in order to reconstruct the original sequence. This is needed as current DNA sequencing
DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, guanine, cytosine, and thymine. Th ...
technology cannot read whole genomes as a continuous sequence, but rather reads small pieces of between 20 and 1000 bases, depending on the technology used. Third generation sequencing technologies such as PacBio or Oxford Nanopore routinely generate sequencing reads >10 kb in length; however, they have a high error rate at approximately 15 percent. Typically the short fragments, called reads, result from shotgun sequencing
In genetics, shotgun sequencing is a method used for sequencing random DNA strands. It is named by analogy with the rapidly expanding, quasi-random shot grouping of a shotgun.
The Sanger sequencing#Method, chain-termination method of DNA sequencin ...
genomic
Genomics is an interdisciplinary field of biology focusing on the structure, function, evolution, mapping, and editing of genomes. A genome is an organism's complete set of DNA, including all of its genes as well as its hierarchical, three-dim ...
DNA, or gene transcripts ( ESTs).
Assembly approaches
Assembly can be broadly categorized into two approaches: ''de novo'' assembly, for genomes which are not similar to any sequenced in the past, and comparative assembly, which uses the existing sequence of a closely related organism as a reference during assembly. Relative to comparative assembly, ''de novo'' assembly is computationally difficult (NP-hard
In computational complexity theory, NP-hardness ( non-deterministic polynomial-time hardness) is the defining property of a class of problems that are informally "at least as hard as the hardest problems in NP". A simple example of an NP-hard pr ...
), making it less favourable for short-read NGS technologies. Within the ''de novo'' assembly paradigm there are two primary strategies for assembly, Eulerian path strategies, and overlap-layout-consensus (OLC) strategies. OLC strategies ultimately try to create a Hamiltonian path through an overlap graph which is an NP-hard problem. Eulerian path strategies are computationally more tractable because they try to find a Eulerian path through a deBruijn graph.
Finishing
Finished genomes are defined as having a single contiguous sequence with no ambiguities representing each replicon.
Annotation
The DNA sequence assembly alone is of little value without additional analysis. Genome annotation
DNA annotation or genome annotation is the process of identifying the locations of genes and all of the coding regions in a genome and determining what those genes do. An annotation (irrespective of the context) is a note added by way of explanati ...
is the process of attaching biological information to sequences
In mathematics, a sequence is an enumerated collection of objects in which repetitions are allowed and order matters. Like a set, it contains members (also called ''elements'', or ''terms''). The number of elements (possibly infinite) is called t ...
, and consists of three main steps:
# identifying portions of the genome that do not code for proteins
# identifying elements on the genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
, a process called gene prediction
In computational biology, gene prediction or gene finding refers to the process of identifying the regions of genomic DNA that encode genes. This includes protein-coding genes as well as RNA genes, but may also include prediction of other functiona ...
, and
# attaching biological information to these elements.
Automatic annotation tools try to perform these steps ''in silico
In biology and other experimental sciences, an ''in silico'' experiment is one performed on computer or via computer simulation. The phrase is pseudo-Latin for 'in silicon' (correct la, in silicio), referring to silicon in computer chips. It ...
'', as opposed to manual annotation (a.k.a. curation) which involves human expertise and potential experimental verification. Ideally, these approaches co-exist and complement each other in the same annotation pipeline
Pipeline may refer to:
Electronics, computers and computing
* Pipeline (computing), a chain of data-processing stages or a CPU optimization found on
** Instruction pipelining, a technique for implementing instruction-level parallelism within a s ...
(also see below
Below may refer to:
*Earth
*Ground (disambiguation)
*Soil
*Floor
*Bottom (disambiguation)
Bottom may refer to:
Anatomy and sex
* Bottom (BDSM), the partner in a BDSM who takes the passive, receiving, or obedient role, to that of the top or ...
).
Traditionally, the basic level of annotation is using BLAST
Blast or The Blast may refer to:
* Explosion, a rapid increase in volume and release of energy in an extreme manner
*Detonation, an exothermic front accelerating through a medium that eventually drives a shock front
Film
* ''Blast'' (1997 film) ...
for finding similarities, and then annotating genomes based on homologues. More recently, additional information is added to the annotation platform. The additional information allows manual annotators to deconvolute discrepancies between genes that are given the same annotation. Some databases use genome context information, similarity scores, experimental data, and integrations of other resources to provide genome annotations through their Subsystems approach. Other databases (e.g. Ensembl
Ensembl genome database project is a scientific project at the European Bioinformatics Institute, which provides a centralized resource for geneticists, molecular biologists and other researchers studying the genomes of our own species and other v ...
) rely on both curated data sources as well as a range of software tools in their automated genome annotation pipeline. ''Structural annotation'' consists of the identification of genomic elements, primarily ORFs
ORFS stands for ''Output RF Spectrum'', where 'RF' stands for Radio Frequency.
The acronym ORFS is used in the context of mobile communication systems, e.g., GSM. It stands for the relationship between (a) the frequency offset from the carrier a ...
and their localisation, or gene structure. ''Functional annotation'' consists of attaching biological information to genomic elements.
Sequencing pipelines and databases
The need for reproducibility and efficient management of the large amount of data associated with genome projects mean that computational pipelines have important applications in genomics.
Research areas
Functional genomics
Functional genomics
Functional genomics is a field of molecular biology that attempts to describe gene (and protein) functions and interactions. Functional genomics make use of the vast data generated by genomic and transcriptomic projects (such as genome sequencing ...
is a field of molecular biology
Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
that attempts to make use of the vast wealth of data produced by genomic projects (such as genome sequencing projects) to describe gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
(and protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
) functions and interactions. Functional genomics focuses on the dynamic aspects such as gene transcription
Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including:
Genetics
* Transcription (biology), the copying of DNA into RNA, the fir ...
, translation
Translation is the communication of the Meaning (linguistic), meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The ...
, and protein–protein interaction
Protein–protein interactions (PPIs) are physical contacts of high specificity established between two or more protein molecules as a result of biochemical events steered by interactions that include electrostatic forces, hydrogen bonding and th ...
s, as opposed to the static aspects of the genomic information such as DNA sequence
DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, guanine, cytosine, and thymine. Th ...
or structures. Functional genomics attempts to answer questions about the function of DNA at the levels of genes, RNA transcripts, and protein products. A key characteristic of functional genomics studies is their genome-wide approach to these questions, generally involving high-throughput methods rather than a more traditional “gene-by-gene” approach.
A major branch of genomics is still concerned with sequencing
In genetics and biochemistry, sequencing means to determine the primary structure (sometimes incorrectly called the primary sequence) of an unbranched biopolymer. Sequencing results in a symbolic linear depiction known as a sequence which succ ...
the genomes of various organisms, but the knowledge of full genomes has created the possibility for the field of functional genomics
Functional genomics is a field of molecular biology that attempts to describe gene (and protein) functions and interactions. Functional genomics make use of the vast data generated by genomic and transcriptomic projects (such as genome sequencing ...
, mainly concerned with patterns of gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...
during various conditions. The most important tools here are microarray
A microarray is a multiplex lab-on-a-chip. Its purpose is to simultaneously detect the expression of thousands of genes from a sample (e.g. from a tissue). It is a two-dimensional array on a solid substrate—usually a glass slide or silicon t ...
s and bioinformatics
Bioinformatics () is an interdisciplinary field that develops methods and software tools for understanding biological data, in particular when the data sets are large and complex. As an interdisciplinary field of science, bioinformatics combi ...
.
Structural genomics
Structural genomics
Structural genomics seeks to describe the 3-dimensional structure of every protein encoded by a given genome. This genome-based approach allows for a high-throughput method of structure determination by a combination of experimental and modeling ...
seeks to describe the 3-dimensional structure of every protein encoded by a given genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
. This genome-based approach allows for a high-throughput method of structure determination by a combination of experimental and modeling approaches. The principal difference between structural genomics and traditional structural prediction is that structural genomics attempts to determine the structure of every protein encoded by the genome, rather than focusing on one particular protein. With full-genome sequences available, structure prediction can be done more quickly through a combination of experimental and modeling approaches, especially because the availability of large numbers of sequenced genomes and previously solved protein structures allow scientists to model protein structure on the structures of previously solved homologs. Structural genomics involves taking a large number of approaches to structure determination, including experimental methods using genomic sequences or modeling-based approaches based on sequence or structural homology
A protein superfamily is the largest grouping (clade) of proteins for which common ancestry can be inferred (see homology). Usually this common ancestry is inferred from structural alignment and mechanistic similarity, even if no sequence similari ...
to a protein of known structure or based on chemical and physical principles for a protein with no homology to any known structure. As opposed to traditional structural biology
Structural biology is a field that is many centuries old which, and as defined by the Journal of Structural Biology, deals with structural analysis of living material (formed, composed of, and/or maintained and refined by living cells) at every le ...
, the determination of a protein structure
Protein structure is the three-dimensional arrangement of atoms in an amino acid-chain molecule. Proteins are polymers specifically polypeptides formed from sequences of amino acids, the monomers of the polymer. A single amino acid monomer ma ...
through a structural genomics effort often (but not always) comes before anything is known regarding the protein function. This raises new challenges in structural bioinformatics
Structural bioinformatics is the branch of bioinformatics that is related to the analysis and prediction of the three-dimensional structure of biological macromolecules such as proteins, RNA, and DNA. It deals with generalizations about macromol ...
, i.e. determining protein function from its 3D structure.
Epigenomics
Epigenomics
Epigenomics is the study of the complete set of epigenetic modifications on the genetic material of a cell, known as the epigenome. The field is analogous to genomics and proteomics, which are the study of the genome and proteome of a cell. Epigen ...
is the study of the complete set of epigenetic
In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
modifications on the genetic material of a cell, known as the epigenome
An epigenome consists of a record of the chemical changes to the DNA and histone proteins of an organism; these changes can be passed down to an organism's offspring via transgenerational stranded epigenetic inheritance. Changes to the epigenome ...
. Epigenetic modifications are reversible modifications on a cell's DNA or histones that affect gene expression without altering the DNA sequence (Russell 2010 p. 475). Two of the most characterized epigenetic modifications are DNA methylation
DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts t ...
and histone modification
In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn ar ...
. Epigenetic modifications play an important role in gene expression and regulation, and are involved in numerous cellular processes such as in differentiation/development and tumorigenesis
Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abno ...
. The study of epigenetics on a global level has been made possible only recently through the adaptation of genomic high-throughput assays.
Metagenomics
Metagenomics
Metagenomics is the study of genetic material recovered directly from environmental or clinical samples by a method called sequencing. The broad field may also be referred to as environmental genomics, ecogenomics, community genomics or microb ...
is the study of ''metagenomes'', genetic material recovered directly from environmental
A biophysical environment is a biotic and abiotic surrounding of an organism or population, and consequently includes the factors that have an influence in their survival, development, and evolution. A biophysical environment can vary in scale f ...
samples. The broad field may also be referred to as environmental genomics, ecogenomics or community genomics. While traditional microbiology
Microbiology () is the scientific study of microorganisms, those being unicellular (single cell), multicellular (cell colony), or acellular (lacking cells). Microbiology encompasses numerous sub-disciplines including virology, bacteriology, prot ...
and microbial genome sequencing
Whole genome sequencing (WGS), also known as full genome sequencing, complete genome sequencing, or entire genome sequencing, is the process of determining the entirety, or nearly the entirety, of the DNA sequence of an organism's genome at a ...
rely upon cultivated clonal cultures
Culture () is an umbrella term which encompasses the social behavior, institutions, and norms found in human societies, as well as the knowledge, beliefs, arts, laws, customs, capabilities, and habits of the individuals in these groups.Tyl ...
, early environmental gene sequencing cloned specific genes (often the 16S rRNA 16S rRNA may refer to:
* 16S ribosomal RNA
16 S ribosomal RNA (or 16 S rRNA) is the RNA component of the 30S subunit of a prokaryotic ribosome ( SSU rRNA). It binds to the Shine-Dalgarno sequence and provides most of the SSU structure.
The g ...
gene) to produce a profile of diversity in a natural sample. Such work revealed that the vast majority of microbial biodiversity had been missed by cultivation-based methods. Recent studies use "shotgun" Sanger sequencing
Sanger sequencing is a method of DNA sequencing that involves electrophoresis and is based on the random incorporation of chain-terminating dideoxynucleotides by DNA polymerase during in vitro DNA replication. After first being developed by Frederi ...
or massively parallel pyrosequencing
Pyrosequencing is a method of DNA sequencing (determining the order of nucleotides in DNA) based on the "sequencing by synthesis" principle, in which the sequencing is performed by detecting the nucleotide incorporated by a DNA polymerase. Pyrosequ ...
to get largely unbiased samples of all genes from all the members of the sampled communities. Because of its power to reveal the previously hidden diversity of microscopic life, metagenomics offers a powerful lens for viewing the microbial world that has the potential to revolutionize understanding of the entire living world.
Model systems
Viruses and bacteriophages
Bacteriophage
A bacteriophage (), also known informally as a ''phage'' (), is a duplodnaviria virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν ('), meaning "to devour". Bacteri ...
s have played and continue to play a key role in bacterial genetics
Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar wor ...
and molecular biology
Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
. Historically, they were used to define gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
structure and gene regulation. Also the first genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
to be sequenced was a bacteriophage
A bacteriophage (), also known informally as a ''phage'' (), is a duplodnaviria virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν ('), meaning "to devour". Bacteri ...
. However, bacteriophage research did not lead the genomics revolution, which is clearly dominated by bacterial genomics. Only very recently has the study of bacteriophage genomes become prominent, thereby enabling researchers to understand the mechanisms underlying phage
A bacteriophage (), also known informally as a ''phage'' (), is a duplodnaviria virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν ('), meaning "to devour". Bacterio ...
evolution. Bacteriophage genome sequences can be obtained through direct sequencing of isolated bacteriophages, but can also be derived as part of microbial genomes. Analysis of bacterial genomes has shown that a substantial amount of microbial DNA consists of prophage A prophage is a bacteriophage (often shortened to "phage") genome that is integrated into the circular bacterial chromosome or exists as an extrachromosomal plasmid within the bacterial cell. Integration of prophages into the bacterial host is the c ...
sequences and prophage-like elements. A detailed database mining of these sequences offers insights into the role of prophages in shaping the bacterial genome: Overall, this method verified many known bacteriophage groups, making this a useful tool for predicting the relationships of prophages from bacterial genomes.
Cyanobacteria
At present there are 24 cyanobacteria
Cyanobacteria (), also known as Cyanophyta, are a phylum of gram-negative bacteria that obtain energy via photosynthesis. The name ''cyanobacteria'' refers to their color (), which similarly forms the basis of cyanobacteria's common name, blu ...
for which a total genome sequence is available. 15 of these cyanobacteria come from the marine environment. These are six ''Prochlorococcus
''Prochlorococcus'' is a genus of very small (0.6 μm) marine cyanobacteria with an unusual pigmentation ( chlorophyll ''a2'' and ''b2''). These bacteria belong to the photosynthetic picoplankton and are probably the most abundant photosynth ...
'' strains, seven marine ''Synechococcus
''Synechococcus'' (from the Greek ''synechos'', in succession, and the Greek ''kokkos'', granule) is a unicellular cyanobacterium that is very widespread in the marine environment. Its size varies from 0.8 to 1.5 µm. The photosynthetic c ...
'' strains, '' Trichodesmium erythraeum'' IMS101 and ''Crocosphaera watsonii
''Crocosphaera watsonii'' (strain WH8501) is an isolate of a species of unicellular (2.5-6 µm diameter), diazotrophic marine cyanobacteria which represent less than 0.1% of the marine microbial population. They thrive in offshore, open-ocea ...
'' WH8501. Several studies have demonstrated how these sequences could be used very successfully to infer important ecological and physiological characteristics of marine cyanobacteria. However, there are many more genome projects currently in progress, amongst those there are further ''Prochlorococcus
''Prochlorococcus'' is a genus of very small (0.6 μm) marine cyanobacteria with an unusual pigmentation ( chlorophyll ''a2'' and ''b2''). These bacteria belong to the photosynthetic picoplankton and are probably the most abundant photosynth ...
'' and marine ''Synechococcus
''Synechococcus'' (from the Greek ''synechos'', in succession, and the Greek ''kokkos'', granule) is a unicellular cyanobacterium that is very widespread in the marine environment. Its size varies from 0.8 to 1.5 µm. The photosynthetic c ...
'' isolates, ''Acaryochloris
''Acaryochloris marina'' is a symbiotic species of the phylum Cyanobacteria that produces chlorophyll d, allowing it to use far-red light, at 770 nm wavelength.
Description
It was first discovered in 1993 from coastal isolates of coral in ...
'' and ''Prochloron
''Prochloron'' (from the Greek ''pro'' (before) and the Greek ''chloros'' (green) ) is a genus of unicellular oxygenic photosynthetic prokaryotes commonly found as an extracellular symbiont on coral reefs, particularly in didemnid ascidians (sea ...
'', the N2-fixing filamentous cyanobacteria '' Nodularia spumigena'', '' Lyngbya aestuarii'' and ''Lyngbya majuscula
''Lyngbya majuscula'' is a species of filamentous cyanobacteria in the genus ''Lyngbya''. It is named after the Dane Hans Christian Lyngbye.
As a result of recent genetic analyses, several new genera were erected from the genus ''Lyngbya'': '' ...
'', as well as bacteriophage
A bacteriophage (), also known informally as a ''phage'' (), is a duplodnaviria virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν ('), meaning "to devour". Bacteri ...
s infecting marine cyanobaceria. Thus, the growing body of genome information can also be tapped in a more general way to address global problems by applying a comparative approach. Some new and exciting examples of progress in this field are the identification of genes for regulatory RNAs, insights into the evolutionary origin of photosynthesis
Photosynthesis is a process used by plants and other organisms to convert light energy into chemical energy that, through cellular respiration, can later be released to fuel the organism's activities. Some of this chemical energy is stored i ...
, or estimation of the contribution of horizontal gene transfer
Horizontal gene transfer (HGT) or lateral gene transfer (LGT) is the movement of genetic material between Unicellular organism, unicellular and/or multicellular organisms other than by the ("vertical") transmission of DNA from parent to offsprin ...
to the genomes that have been analyzed.
Applications
Genomics has provided applications in many fields, including medicine
Medicine is the science and practice of caring for a patient, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care pract ...
, biotechnology
Biotechnology is the integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof and molecular analogues for products and services. The term ''biotechnology'' was first used b ...
, anthropology
Anthropology is the scientific study of humanity, concerned with human behavior, human biology, cultures, societies, and linguistics, in both the present and past, including past human species. Social anthropology studies patterns of behavi ...
and other social sciences
Social science is one of the branches of science, devoted to the study of societies and the relationships among individuals within those societies. The term was formerly used to refer to the field of sociology, the original "science of soci ...
.
Genomic medicine
Next-generation genomic technologies allow clinicians and biomedical researchers to drastically increase the amount of genomic data collected on large study populations. When combined with new informatics approaches that integrate many kinds of data with genomic data in disease research, this allows researchers to better understand the genetic bases of drug response and disease. Early efforts to apply the genome to medicine included those by a Stanford team led by Euan Ashley who developed the first tools for the medical interpretation of a human genome. The Genomes2People research program at Brigham and Women’s Hospital
Brigham and Women's Hospital (BWH) is the second largest teaching hospital of Harvard Medical School and the largest hospital in the Longwood Medical Area in Boston, Massachusetts. Along with Massachusetts General Hospital, it is one of the two f ...
, Broad Institute
The Eli and Edythe L. Broad Institute of MIT and Harvard (IPA: , pronunciation respelling: ), often referred to as the Broad Institute, is a biomedical and genomic research center located in Cambridge, Massachusetts, Cambridge, Massachusetts, U ...
and Harvard Medical School was established in 2012 to conduct empirical research in translating genomics into health. Brigham and Women's Hospital
Brigham and Women's Hospital (BWH) is the second largest teaching hospital of Harvard Medical School and the largest hospital in the Longwood Medical and Academic Area, Longwood Medical Area in Boston, Massachusetts. Along with Massachusetts Gener ...
opened a Preventive Genomics Clinic in August 2019, with Massachusetts General Hospital
Massachusetts General Hospital (Mass General or MGH) is the original and largest teaching hospital of Harvard Medical School located in the West End neighborhood of Boston, Massachusetts. It is the third oldest general hospital in the United Stat ...
following a month later. The ''All of Us'' research program aims to collect genome sequence data from 1 million participants to become a critical component of the precision medicine research platform.
Synthetic biology and bioengineering
The growth of genomic knowledge has enabled increasingly sophisticated applications of synthetic biology
Synthetic biology (SynBio) is a multidisciplinary area of research that seeks to create new biological parts, devices, and systems, or to redesign systems that are already found in nature.
It is a branch of science that encompasses a broad ran ...
. In 2010 researchers at the J. Craig Venter Institute announced the creation of a partially synthetic species of bacterium
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
, ''Mycoplasma laboratorium
''Mycoplasma laboratorium'' or Synthia refers to a synthetic strain of bacterium. The project to build the new bacterium has evolved since its inception. Initially the goal was to identify a minimal set of genes that are required to sustain li ...
'', derived from the genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
of ''Mycoplasma genitalium
''Mycoplasma genitalium'' (''MG'', commonly known as Mgen) is a sexually transmitted, small and pathogenic bacterium that lives on the mucous epithelial cells of the urinary and genital tracts in humans. Medical reports published in 2007 and 201 ...
''.
Population and conservation genomics
Population genomics Population genomics is the large-scale comparison of DNA sequences of populations. Population genomics is a neologism that is associated with population genetics. Population genomics studies genome-wide effects to improve our understanding of micro ...
has developed as a popular field of research, where genomic sequencing methods are used to conduct large-scale comparisons of DNA sequences among populations - beyond the limits of genetic markers such as short-range PCR products or microsatellites
A microsatellite is a tract of repetitive DNA in which certain DNA motifs (ranging in length from one to six or more base pairs) are repeated, typically 5–50 times. Microsatellites occur at thousands of locations within an organism's genome. ...
traditionally used in 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 pop ...
. Population genomics studies genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
-wide effects to improve our understanding of microevolution
Microevolution is the change in allele frequencies that occurs over time within a population. This change is due to four different processes: mutation, selection (natural and artificial), gene flow and genetic drift. This change happens over a r ...
so that we may learn the phylogenetic
In biology, phylogenetics (; from Greek φυλή/ φῦλον [] "tribe, clan, race", and wikt:γενετικός, γενετικός [] "origin, source, birth") is the study of the evolutionary history and relationships among or within groups o ...
history and demography
Demography () is the statistics, statistical study of populations, especially human beings.
Demographic analysis examines and measures the dimensions and Population dynamics, dynamics of populations; it can cover whole societies or groups ...
of a population. Population genomic methods are used for many different fields including evolutionary biology
Evolutionary biology is the subfield of biology that studies the evolutionary processes (natural selection, common descent, speciation) that produced the diversity of life on Earth. It is also defined as the study of the history of life fo ...
, ecology
Ecology () is the study of the relationships between living organisms, including humans, and their physical environment. Ecology considers organisms at the individual, population, community, ecosystem, and biosphere level. Ecology overlaps wi ...
, biogeography
Biogeography is the study of the distribution of species and ecosystems in geographic space and through geological time. Organisms and biological communities often vary in a regular fashion along geographic gradients of latitude, elevation, ...
, conservation biology
Conservation biology is the study of the conservation of nature and of Earth's biodiversity with the aim of protecting species, their habitats, and ecosystems from excessive rates of extinction and the erosion of biotic interactions. It is an int ...
and fisheries management
The goal of fisheries management is to produce sustainable biological, environmental and socioeconomic benefits from renewable aquatic resources. Wild fisheries are classified as renewable when the organisms of interest (e.g., fish, shellfish, am ...
. Similarly, landscape genomics Landscape genomics is one of many strategies used to identify relationships between environmental factors and the genetic adaptation of organisms in response to these factors. Landscape genomics combines aspects of landscape ecology, population gene ...
has developed from landscape genetics
Landscape genetics is the scientific discipline that combines population genetics and landscape ecology. It broadly encompasses any study that analyses plant or animal population genetic data in conjunction with data on the landscape features and ...
to use genomic methods to identify relationships between patterns of environmental and genetic variation.
Conservationists can use the information gathered by genomic sequencing in order to better evaluate genetic factors key to species conservation, such as the genetic diversity
Genetic diversity is the total number of genetic characteristics in the genetic makeup of a species, it ranges widely from the number of species to differences within species and can be attributed to the span of survival for a species. It is dis ...
of a population or whether an individual is heterozygous for a recessive inherited genetic disorder. By using genomic data to evaluate the effects of evolutionary process
Evolution is change in the heritable characteristics of biological populations over successive generations. These characteristics are the expressions of genes, which are passed on from parent to offspring during reproduction. Variation t ...
es and to detect patterns in variation throughout a given population, conservationists can formulate plans to aid a given species without as many variables left unknown as those unaddressed by standard genetic approaches.
See also
* Cognitive genomics
Cognitive genomics (or neurative genomics) is the sub-field of genomics pertaining to cognitive function in which the genes and non-coding sequences of an organism's genome related to the health and activity of the brain are studied. By applying ...
* Computational genomics Computational genomics refers to the use of computational and statistical analysis to decipher biology from genome sequences and related data, including both DNA and RNA sequence as well as other "post-genomic" data (i.e., experimental data obtained ...
* Epigenomics
Epigenomics is the study of the complete set of epigenetic modifications on the genetic material of a cell, known as the epigenome. The field is analogous to genomics and proteomics, which are the study of the genome and proteome of a cell. Epigen ...
* Functional genomics
Functional genomics is a field of molecular biology that attempts to describe gene (and protein) functions and interactions. Functional genomics make use of the vast data generated by genomic and transcriptomic projects (such as genome sequencing ...
* GeneCalling In the field of genomics, GeneCalling is an open-platform mRNA transcriptional profiling technique. The GeneCalling protocol measures levels of cDNA, which are correlated with gene expression levels of specific transcripts. Differences between gene ...
, an mRNA profiling technology
* Genomics of domestication
* Genetics in fiction
Aspects of genetics including mutation, hybridisation, cloning, genetic engineering, and eugenics have appeared in fiction since the 19th century.
Genetics is a young science, having started in 1900 with the rediscovery of Gregor Mendel's stu ...
* Glycomics Glycomics is the comprehensive study of glycomes (the entire complement of sugars, whether free or present in more complex molecules of an organism), including genetic, physiologic, pathologic, and other aspects. Glycomics "is the systematic study o ...
* Immunomics
Immunomics is the study of immune system regulation and response to pathogens using genome-wide approaches. With the rise of genomic and proteomic technologies, scientists have been able to visualize biological networks and infer interrelationshi ...
* Metagenomics
Metagenomics is the study of genetic material recovered directly from environmental or clinical samples by a method called sequencing. The broad field may also be referred to as environmental genomics, ecogenomics, community genomics or microb ...
* Pathogenomics Pathogenomics is a field which uses high-throughput screening technology and bioinformatics to study encoded microbe resistance, as well as virulence factors (VFs), which enable a microorganism to infect a host and possibly cause disease. This inclu ...
* Personal genomics
Personal genomics or consumer genetics is the branch of genomics concerned with the sequencing, analysis and interpretation of the genome of an individual. The genotyping stage employs different techniques, including single-nucleotide polymorphi ...
* Proteomics
Proteomics is the large-scale study of proteins. Proteins are vital parts of living organisms, with many functions such as the formation of structural fibers of muscle tissue, enzymatic digestion of food, or synthesis and replication of DNA. In ...
* Transcriptomics
Transcriptomics technologies are the techniques used to study an organism's transcriptome, the sum of all of its RNA transcripts. The information content of an organism is recorded in the DNA of its genome and expressed through transcription. He ...
* Venomics
Venomics is the large-scale study of proteins associated with venom. Venom is a toxic substance secreted by animals, which is typically injected either offensively or defensively into prey or aggressors, respectively.
Venom is produced in a specia ...
* Psychogenomics
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" co ...
* Whole genome sequencing
Whole genome sequencing (WGS), also known as full genome sequencing, complete genome sequencing, or entire genome sequencing, is the process of determining the entirety, or nearly the entirety, of the DNA sequence of an organism's genome at a s ...
*Thomas Roderick
Thomas Huston Roderick, Ph.D., (1930–2013) was an American geneticist who coined the term “genomics".
Dr. Roderick earned degrees from the University of Michigan in philosophy in 1952 and zoology in 1953 and went on receive a Ph.D. from the Un ...
References
Further reading
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External links
Annual Review of Genomics and Human Genetics
BMC Genomics
A BMC journal on Genomics
Genomics journal
Genomics.org
An openfree genomics portal.
NHGRI
US government's genome institute
JCVI Comprehensive Microbial Resource
KoreaGenome.org
The first Korean Genome published and the sequence is available freely.
GenomicsNetwork
Looks at the development and use of the science and technologies of genomics.
Institute for Genome Sciences
Genomics research.
MIT OpenCourseWare HST.512 Genomic Medicine
A free, self-study course in genomic medicine. Resources include audio lectures and selected lecture notes.
ENCODE threads explorer
Machine learning approaches to genomics. Nature (journal)
''Nature'' is a British weekly scientific journal founded and based in London, England. As a multidisciplinary publication, ''Nature'' features peer-reviewed research from a variety of academic disciplines, mainly in science and technology. ...
Global map of genomics laboratories
Genomics: Scitable by nature education
Learn All About Genetics Online
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