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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 phys ...
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 ...
, the consensus sequence (or canonical sequence) is the calculated order of most frequent residues, either
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 biomolecu ...
or
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 ...
, found at each position in a
sequence alignment In bioinformatics, a sequence alignment is a way of arranging the sequences of DNA, RNA, or protein to identify regions of similarity that may be a consequence of functional, structural, or evolutionary relationships between the sequences. Al ...
. It serves as a simplified representation of the population. It represents the results of multiple
sequence alignment In bioinformatics, a sequence alignment is a way of arranging the sequences of DNA, RNA, or protein to identify regions of similarity that may be a consequence of functional, structural, or evolutionary relationships between the sequences. Al ...
s in which related sequences are compared to each other and similar sequence motifs are calculated. Such information is important when considering sequence-dependent enzymes such as RNA polymerase.Pierce, Benjamin A. 2002. Genetics : A Conceptual Approach. 1st ed. New York: W.H. Freeman and Co.


Biological significance

A protein binding site, represented by a consensus sequence, may be a short sequence of
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 biomolecu ...
s which is found several times in 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 ...
and is thought to play the same role in its different locations. For example, many transcription factors recognize particular patterns in the promoters of the
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 b ...
s they regulate. In the same way,
restriction enzymes A restriction enzyme, restriction endonuclease, REase, ENase or'' restrictase '' is an enzyme that cleaves DNA into fragments at or near specific recognition sites within molecules known as restriction sites. Restriction enzymes are one class ...
usually have palindromic consensus sequences, usually corresponding to the site where they cut the DNA.
Transposons A transposable element (TE, transposon, or jumping gene) is a nucleic acid sequence in DNA that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size. Tran ...
act in much the same manner in their identification of target sequences for transposition. Finally, splice sites (sequences immediately surrounding the exon- intron boundaries) can also be considered as consensus sequences. Thus a consensus sequence is a model for a putative DNA binding site: it is obtained by aligning all known examples of a certain recognition site and defined as the idealized sequence that represents the predominant base at each position. All the actual examples shouldn't differ from the consensus by more than a few substitutions, but counting mismatches in this way can lead to inconsistencies. Any mutation allowing a mutated nucleotide in the core promoter sequence to look more like the consensus sequence is known as an up mutation. This kind of mutation will generally make the promoter stronger, and thus the RNA polymerase forms a tighter bind to the DNA it wishes to transcribe and transcription is up-regulated. On the contrary, mutations that destroy conserved nucleotides in the consensus sequence are known as down mutations. These types of mutations down-regulate transcription since RNA polymerase can no longer bind as tightly to the core promoter sequence.


Sequence analysis

Developing software for pattern recognition is a major topic in
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 work ...
,
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 phys ...
, 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 ...
. Specific
sequence motif In biology, a sequence motif is a nucleotide or amino-acid sequence pattern that is widespread and usually assumed to be related to biological function of the macromolecule. For example, an ''N''-glycosylation site motif can be defined as ' ...
s can function as
regulatory sequence A regulatory sequence is a segment of a nucleic acid molecule which is capable of increasing or decreasing the expression of specific genes within an organism. Regulation of gene expression is an essential feature of all living organisms and ...
s controlling biosynthesis, or as signal sequences that direct a molecule to a specific site within the cell or regulate its maturation. Since the regulatory function of these sequences is important, they are thought to be conserved across long periods of
evolution 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 ...
. In some cases, evolutionary relatedness can be estimated by the amount of conservation of these sites.


Notation

The conserved sequence motifs are called consensus sequences and they show which residues are conserved and which residues are variable. Consider the following example DNA sequence: :A TYR In this notation, A means that an A is always found in that position; Tstands for either C or T; N stands for any base; and means any base except A. Y represents any
pyrimidine Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The othe ...
, and R indicates any
purine Purine is a heterocyclic aromatic organic compound that consists of two rings ( pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which include substituted purines ...
. In this example, the notation Tdoes not give any indication of the relative frequency of C or T occurring at that position. An alternative method of representing a consensus sequence uses a
sequence logo In bioinformatics, a sequence logo is a graphical representation of the sequence conservation of nucleotides (in a strand of DNA/ RNA) or amino acids (in protein sequences). A sequence logo is created from a collection of aligned sequences and d ...
. This is a graphical representation of the consensus sequence, in which the size of a symbol is related to the frequency that a given nucleotide (or amino acid) occurs at a certain position. In sequence logos the more conserved the residue, the larger the symbol for that residue is drawn; the less frequent, the smaller the symbol. Sequence logos can be generated usin
WebLogo
or using th
Gestalt Workbench
a publicly available visualization tool written by Gustavo Glusman at th
Institute for Systems Biology


Software

Bioinformatics tools are able to calculate and visualize consensus sequences. Examples of the tools are JalView and UGENE.


See also

*
Position-specific scoring matrix A position weight matrix (PWM), also known as a position-specific weight matrix (PSWM) or position-specific scoring matrix (PSSM), is a commonly used representation of motifs (patterns) in biological sequences. PWMs are often derived from a set ...
* Regular expression — denoting multiple sequences of symbols in
formal language In logic, mathematics, computer science, and linguistics, a formal language consists of words whose letters are taken from an alphabet and are well-formed according to a specific set of rules. The alphabet of a formal language consists of sym ...
theory *
Sequence motif In biology, a sequence motif is a nucleotide or amino-acid sequence pattern that is widespread and usually assumed to be related to biological function of the macromolecule. For example, an ''N''-glycosylation site motif can be defined as ' ...
*
Sequence logo In bioinformatics, a sequence logo is a graphical representation of the sequence conservation of nucleotides (in a strand of DNA/ RNA) or amino acids (in protein sequences). A sequence logo is created from a collection of aligned sequences and d ...


References

{{Reflist Bioinformatics DNA