Nucleic acid sequence

Source: Wikipedia, the free encyclopedia.
Nucleic acid primary structureNucleic acid secondary structureNucleic acid tertiary structureNucleic acid quaternary structure
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The image above contains clickable links
Interactive image of nucleic acid structure (primary, secondary, tertiary, and quaternary) using DNA helices and examples from the VS ribozyme and telomerase and nucleosome. (PDB: ADNA, 1BNA, 4OCB, 4R4V, 1YMO, 1EQZ​)

A nucleic acid sequence is a succession of

covalent structure of the entire molecule. For this reason, the nucleic acid sequence is also termed the primary structure
.

The sequence represents genetic 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". However there is no parallel concept of secondary or tertiary sequence.

Nucleotides

Chemical structure of RNA
mRNA 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 structures such as the famed double helix.

The possible letters are A, C, G, and T, representing the four

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

Main article: Nucleic acid notation

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]

For example, W means that either an adenine or a thymine could occur in that position without impairing the sequence's functionality.

List of symbols
Symbol[2] Meaning/derivation Possible bases Complement
A Adenine A 1 T (or U)
C Cytosine C G
G Guanine G C
T Thymine T A
U Uracil U A
W Weak A T 2 W
S Strong C G S
M aMino A C K
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 3 V
D not C (D comes after C) A G T H
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

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
.

Example of comparing and determining the % difference between two nucleotide sequences
  • AATCCGCTAG
  • AAACCCTTAG

Given the two 10-nucleotide sequences, line them up and compare the differences between them. Calculate the percent difference by taking the number of differences between the DNA bases divided by the total number of nucleotides. In this case there are three differences in the 10 nucleotide sequence. Thus there is a 30% difference.

Biological significance

translated into amino acid sequences in proteins
.
Further information: Genetic code and Central dogma of molecular biology

In biological systems, nucleic acids contain information which is used by a living

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

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

Electropherogram printout from automated sequencer for determining part of a DNA sequence
Main article: DNA sequencing

DNA sequencing is the process of determining the

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 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.

Digital representation

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 actual DNA using artificial gene synthesis.

Sequence analysis

Main article: Sequence analysis

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

Genetic testing

Main article: Genetic testing

The DNA in an organism's

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

Main article: Sequence alignment

In bioinformatics, a sequence alignment is a way of arranging the sequences of

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]

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

Main article: Sequence motif

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

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

References

  1. ^
    PMID 2417239
    .
  2. ^ Nomenclature Committee of the International Union of Biochemistry (NC-IUB) (1984). "Nomenclature for Incompletely Specified Bases in Nucleic Acid Sequences". Retrieved 2008-02-04.
  3. ^ "BIOL2060: Translation". mun.ca.
  4. ^ "Research". uw.edu.pl.
  5. PMID 1557408
    .
  6. ^ "What is genetic testing?". Genetics Home Reference. 16 March 2015. Archived from the original on 29 May 2006. Retrieved 19 May 2010.
  7. ^ "Genetic Testing". nih.gov.
  8. ^ "Definitions of Genetic Testing". Definitions of Genetic Testing (Jorge Sequeiros and Bárbara Guimarães). EuroGentest Network of Excellence Project. 2008-09-11. Archived from the original on February 4, 2009. Retrieved 2008-08-10.
  9. ISBN 0-87969-608-7
    .
  10. PMID 11337480
    .
  11. S2CID 30962295
    .
  12. PMID 9649444
    .
  13. PMID 9106664
    .
  14. S2CID 4162567
    .
  15. PMID 3313277
    .
  16. S2CID 9982829
    .
  17. ^
    PMID 24278218
    .
  18. PMID 25984837
    .
  19. PMID 12050064
    .

External links

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