Nucleic acid sequence

Nucleic acid primary structureNucleic acid secondary structureNucleic acid tertiary structureNucleic acid quaternary structure
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Interactive image of nucleic acid structure (primary, secondary, tertiary, and quaternary) using DNA helices and examples from the VS ribozyme and telomerase and nucleosome. (1EQZ​)


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 structure.

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 tertiary sequence.

Nucleotides

Chemical structure of RNA
A series of codons in part of a mRNA molecule. Each codon consists of three nucleotides, usually representing a single amino acid.

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, thyminecovalently 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.

  • 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 = 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 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).[2][3] 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.[4] Similarly, deamination of cytosine results in uracil.

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