Nucleic acid sequence

A nucleic acid sequence is a succession of bases signified

by a series of a set of five different letters that indicate the
order of nucleotides forming alleles 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 structure.

The sequence has capacity to represent information.

Biological deoxyribonucleic acid represents the information
which directs the functions of an organism.

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 tertiary sequence.

Nucleotides
Nucleic acids consist of a chain of linked units called
Interactive image of nucleic acid
nucleotides. Each nucleotide consists of three subunits: a
structure (primary, secondary, tertiary,
phosphate group and a sugar (ribose in the case of RNA,
and quaternary) using DNA helices and
deoxyribose in DNA) make up the backbone of the nucleic
examples from the VS ribozyme and
acid strand, and attached to the sugar is one of a set of
telomerase and nucleosome. (PDB: ADNA (ht
nucleobases. The nucleobases are important in base pairing
tps://www.rcsb.org/structure/ADNA), 1BNA (h
of strands to form higher-level secondary and tertiary
ttps://www.rcsb.org/structure/1BNA), 4OCB
structures such as the famed double helix.
(https://www.rcsb.org/structure/4OCB), 4R4V
(https://www.rcsb.org/structure/4R4V), 1YMO
The possible letters are A, C, G, and T, representing the
(https://www.rcsb.org/structure/1YMO), 1EQZ
four nucleotide bases of a DNA strand – adenine, cytosine,
(https://www.rcsb.org/structure/1EQZ)​)
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 DNA is considered the sense strand, then the other
strand, considered the antisense strand, will have the
complementary sequence to the sense strand.

Notation

Comparing and determining  % difference between two nucleotide

sequences. Chemical structure of RNA

AATCCGCTAG
AAACCCTTAG
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:[1]

A series of codons in part of a

mRNA molecule. Each codon
consists of three nucleotides,
usually representing a single amino
acid.
 Symbol[2] Description Bases represented Complement

A Adenine A T

C Cytosine C G

G Guanine G 1 C
T Thymine T A

U Uracil U A

W Weak A T W
S Strong C G S

M aMino A C K
2
K Keto G T M
R puRine A G Y

Y pYrimidine C T R

B not A (B comes after A) C G T V

D not C (D comes after C) A G T H
3
H not G (H comes after G) A C T D

V not T (V comes after T and U) A C G B

N any Nucleotide (not a gap) A C G T 4 N

Z Zero 0 Z

These symbols are also valid for RNA, except with U (uracil) replacing T (thymine).[1]

Apart from adenine (A), cytosine (C), guanine (G), thymine (T) and uracil (U), DNA 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 7-methylguanosine (m7G).[3][4]
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, and xanthine is produced from guanine.[5] Similarly, deamination of cytosine results in uracil.

Biological significance
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 mRNA molecules, which travel to the
ribosome where the mRNA 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 strand.

Sequence determination
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
A depiction of the genetic code,
fundamental research into why and how organisms live, as well as in
by which the information
applied subjects. Because of the importance of DNA to living things, contained in nucleic acids are
knowledge of a DNA sequence may be useful in practically any translated into amino acid
biological research. For example, in medicine it can be used to identify, sequences in proteins.
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

DNA by 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 Electropherogram printout from automated
during RNA editing) is read as a G, and 5-methyl-cytosine sequencer for determining part of a DNA
(created from cytosine by DNA methylation) is read as a C. sequence
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.

Digital representation

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 actual
DNA using artificial gene synthesis. Genetic sequence in digital format.

Sequence analysis
Digital genetic sequences may be analyzed using the tools of bioinformatics to attempt to determine its
function.

Genetic testing

The 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.[6] 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 developed.[7][8]

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.[9] 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[10] that this
region has structural or functional importance. Although DNA and 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.[11]

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 differences 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.

Sequence motifs

Frequently the primary structure encodes motifs that are of functional importance. Some examples of
sequence motifs are: the C/D[12] and H/ACA boxes[13] of snoRNAs, Sm binding site found in
spliceosomal RNAs such as U1, U2, U4, U5, U6, U12 and U3, the Shine-Dalgarno sequence,[14] the
Kozak consensus sequence[15] and the RNA polymerase III terminator.[16]

Sequence entropy

In bioinformatics, a sequence entropy, also known as sequence complexity or information profile,[17] 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.[17][18] [19]

See also
Gene structure
Nucleic acid structure determination
Quaternary numeral system
Single-nucleotide polymorphism (SNP)

References
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m.qmul.ac.uk/iubmb/misc/naseq.html), NC-IUB, 1984.
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External links
A bibliography on features, patterns, correlations in DNA and protein texts (https://web.archiv
e.org/web/20080509072853/http://www.nslij-genetics.org/dnacorr/)

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