A nucleic acid sequence is a succession of letters that indicate the
order of nucleotides within a
DNA (using GACT) or
RNA (GACU) molecule.
By convention, sequences are usually presented from the 5' end to the
3' end. For DNA, the sense strand is used. Because nucleic acids are
normally linear (unbranched) polymers, specifying the sequence is
equivalent to defining the covalent structure of the entire molecule.
For this reason, the nucleic acid sequence is also termed the primary
The sequence has capacity to represent information. Biological
deoxyribonucleic acid represents the information which directs the
functions of a living thing.
Nucleic acids also have a secondary structure and tertiary structure.
Primary structure is sometimes mistakenly referred to as primary
sequence. Conversely, there is no parallel concept of secondary or
2 Biological significance
3 Sequence determination
3.1 Digital representation
4 Sequence analysis
4.1 Genetic testing
4.2 Sequence alignment
4.3 Sequence motifs
4.4 Long range correlations
4.5 Sequence entropy
5 See also
7 External links
Chemical structure of RNA
A series of codons in part of a m
RNA molecule. Each codon consists of
three nucleotides, usually representing a single amino acid.
Main article: Nucleotide
Nucleic acids consist of a chain of linked units called nucleotides.
Each nucleotide consists of three subunits: a phosphate group and a
sugar (ribose in the case of RNA, deoxyribose in DNA) make up the
backbone of the nucleic acid strand, and attached to the sugar is one
of a set of nucleobases. The nucleobases are important in base pairing
of strands to form higher-level secondary and tertiary structure such
as the famed double helix.
The possible letters are A, C, G, and T, representing the four
nucleotide bases of a
DNA strand — adenine, cytosine, guanine,
thymine — covalently linked to a phosphodiester backbone. In the
typical case, the sequences are printed abutting one another without
gaps, as in the sequence AAAGTCTGAC, read left to right in the 5' to
3' direction. With regards to transcription, a sequence is on the
coding strand if it has the same order as the transcribed RNA.
One sequence can be complementary to another sequence, meaning that
they have the base on each position in the complementary (i.e. A to T,
C to G) and in the reverse order. For example, the complementary
sequence to TTAC is GTAA. If one strand of the double-stranded
considered the sense strand, then the other strand, considered the
antisense strand, will have the complementary sequence to the sense
Nucleic acid notation
Comparing and determining % difference between two nucleotide
Given the two 10-nucleotide sequences, line them up and compare the
differences between them. Calculate the percent similarity by taking
the number of different
DNA bases divided by the total number of
nucleotides. In the above case, there are three differences in the 10
nucleotide sequence. Therefore, divide 7/10 to get the 70% similarity
and subtract that from 100% to get a 30% difference.
While A, T, C, and G represent a particular nucleotide at a position,
there are also letters that represent ambiguity which are used when
more than one kind of nucleotide could occur at that position. The
rules of the International Union of Pure and Applied Chemistry (IUPAC)
are as follows:
A = adenine
C = cytosine
G = guanine
T = thymine
R = G A (purine)
Y = T C (pyrimidine)
K = G T (keto)
M = A C (amino)
S = G C (strong bonds)
W = A T (weak bonds)
B = G T C (all but A)
D = G A T (all but C)
H = A C T (all but G)
V = G C A (all but T)
N = A G C T (any)
These symbols are also valid for RNA, except with U (uracil) replacing
Apart from adenine (A), cytosine (C), guanine (G), thymine (T) and
RNA also contain bases that have been modified
after the nucleic acid chain has been formed. In DNA, the most common
modified base is 5-methylcytidine (m5C). In RNA, there are many
modified bases, including pseudouridine (Ψ), dihydrouridine (D),
inosine (I), ribothymidine (rT) and
Hypoxanthine and xanthine are two of the many bases created through
mutagen presence, both of them through deamination (replacement of the
amine-group with a carbonyl-group).
Hypoxanthine is produced from
adenine, xanthine from guanine. Similarly, deamination of cytosine
results in uracil.
A depiction of the genetic code, by which the information contained in
nucleic acids are translated into amino acid sequences in proteins.
Genetic code and Central dogma of molecular
In biological systems, nucleic acids contain information which is used
by a living cell to construct specific proteins. The sequence of
nucleobases on a nucleic acid strand is translated by cell machinery
into a sequence of amino acids making up a protein strand. Each group
of three bases, called a codon, corresponds to a single amino acid,
and there is a specific genetic code by which each possible
combination of three bases corresponds to a specific amino acid.
The central dogma of molecular biology outlines the mechanism by which
proteins are constructed using information contained in nucleic acids.
DNA is transcribed into m
RNA molecules, which travels to the ribosome
where the m
RNA is used as a template for the construction of the
protein strand. Since nucleic acids can bind to molecules with
complementary sequences, there is a distinction between "sense"
sequences which code for proteins, and the complementary "antisense"
sequence which is by itself nonfunctional, but can bind to the sense
Electropherogram printout from automated sequencer for determining
part of a
DNA sequencing is the process of determining the nucleotide sequence
of a given
DNA fragment. The sequence of the
DNA of a living thing
encodes the necessary information for that living thing to survive and
reproduce. Therefore, determining the sequence is useful in
fundamental research into why and how organisms live, as well as in
applied subjects. Because of the importance of
DNA to living things,
knowledge of a
DNA sequence may be useful in practically any
biological research. For example, in medicine it can be used to
identify, diagnose and potentially develop treatments for genetic
diseases. Similarly, research into pathogens may lead to treatments
for contagious diseases.
Biotechnology is a burgeoning discipline,
with the potential for many useful products and services.
RNA is not sequenced directly. Instead, it is copied to a
reverse transcriptase, and this
DNA is then sequenced.
Current sequencing methods rely on the discriminatory ability of DNA
polymerases, and therefore can only distinguish four bases. An inosine
(created from adenosine during
RNA editing) is read as a G, and
5-methyl-cytosine (created from cytosine by
DNA methylation) is read
as a C. With current technology, it is difficult to sequence small
amounts of DNA, as the signal is too weak to measure. This is overcome
by polymerase chain reaction (PCR) amplification.
Genetic sequence in digital format.
Once a nucleic acid sequence has been obtained from an organism, it is
stored in silico in digital format. Digital genetic sequences may be
stored in sequence databases, be analyzed (see Sequence analysis
below), be digitally altered and be used as templates for creating new
DNA using artificial gene synthesis.
Main article: Sequence analysis
Digital genetic sequences may be analyzed using the tools of
bioinformatics to attempt to determine its function.
Main article: Genetic testing
DNA in an organism's genome can be analyzed to diagnose
vulnerabilities to inherited diseases, and can also be used to
determine a child's paternity (genetic father) or a person's ancestry.
Normally, every person carries two variations of every gene, one
inherited from their mother, the other inherited from their father.
The human genome is believed to contain around 20,000 - 25,000 genes.
In addition to studying chromosomes to the level of individual genes,
genetic testing in a broader sense includes biochemical tests for the
possible presence of genetic diseases, or mutant forms of genes
associated with increased risk of developing genetic disorders.
Genetic testing identifies changes in chromosomes, genes, or
proteins. Usually, testing is used to find changes that are
associated with inherited disorders. The results of a genetic test can
confirm or rule out a suspected genetic condition or help determine a
person's chance of developing or passing on a genetic disorder.
Several hundred genetic tests are currently in use, and more are being
Main article: 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 due to functional, structural, or evolutionary
relationships between the sequences. If two sequences in an
alignment share a common ancestor, mismatches can be interpreted as
point mutations and gaps as insertion or deletion mutations (indels)
introduced in one or both lineages in the time since they diverged
from one another. In sequence alignments of proteins, the degree of
similarity between amino acids occupying a particular position in the
sequence can be interpreted as a rough measure of how conserved a
particular region or sequence motif is among lineages. The absence of
substitutions, or the presence of only very conservative substitutions
(that is, the substitution of amino acids whose side chains have
similar biochemical properties) in a particular region of the
sequence, suggest that this region has structural or functional
RNA nucleotide bases are more similar to
each other than are amino acids, the conservation of base pairs can
indicate a similar functional or structural role.
Computational phylogenetics makes extensive use of sequence alignments
in the construction and interpretation of phylogenetic trees, which
are used to classify the evolutionary relationships between homologous
genes represented in the genomes of divergent species. The degree to
which sequences in a query set differ is qualitatively related to the
sequences' evolutionary distance from one another. Roughly speaking,
high sequence identity suggests that the sequences in question have a
comparatively young most recent common ancestor, while low identity
suggests that the divergence is more ancient. This approximation,
which reflects the "molecular clock" hypothesis that a roughly
constant rate of evolutionary change can be used to extrapolate the
elapsed time since two genes first diverged (that is, the coalescence
time), assumes that the effects of mutation and selection are constant
across sequence lineages. Therefore, it does not account for possible
difference among organisms or species in the rates of
DNA repair or
the possible functional conservation of specific regions in a
sequence. (In the case of nucleotide sequences, the molecular clock
hypothesis in its most basic form also discounts the difference in
acceptance rates between silent mutations that do not alter the
meaning of a given codon and other mutations that result in a
different amino acid being incorporated into the protein.) More
statistically accurate methods allow the evolutionary rate on each
branch of the phylogenetic tree to vary, thus producing better
estimates of coalescence times for genes.
Main article: Sequence motif
Frequently the primary structure encodes motifs that are of functional
importance. Some examples of sequence motifs are: the C/D and
H/ACA boxes of snoRNAs, Sm binding site found in spliceosomal RNAs
such as U1, U2, U4, U5, U6, U12 and U3, the Shine-Dalgarno
sequence, the Kozak consensus sequence and the
Long range correlations
Peng  found the existence of long-range correlations in the
non-coding base pair sequences of DNA. In contrast, such correlations
seem not to appear in coding
Main article: Sequence entropy
In Bioinformatics, a sequence entropy, also known as sequence
complexity or information profile, is a numerical sequence
providing a quantitative measure of the local complexity of a DNA
sequence, independently of the direction of processing. The
manipulations of the information profiles enable the analysis of the
sequences using alignment-free techniques, such as for example in
motif and rearrangements detection. 
Quaternary numeral system
Single-nucleotide polymorphism (SNP)
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