Structure of Nucleic Acids (DNA and RNA)

Information-carrying molecules

Both DNA and RNA are molecules that are specialised for carrying genetic information.

DNA acts as a store of genetic information within the cell. In eukaryotes this is all packaged up (together with proteins) into chromosomes within the nucleus, and in prokaryotes the DNA remains unpackaged in the cytoplasm.

One form of RNA transfers genetic information from DNA to ribosomes which assemble proteins using another form of RNA. In fact ribosomes are composed of another form of RNA and proteins.

This has been called "The Central Dogma of Molecular Biology": DNA makes RNA makes proteins.
The genetic code for the production of proteins is common to all living organisms, and viruses.

Long-term versus short-term

Some aspects of the molecular structure of DNA seem to give it more long-term stability than RNA, which is produced and broken down more quickly.


Forms of RNA (involved in transcription and translation)
Messenger RNA (mRNA)
Transfer RNA (tRNA)
Ribosomal RNA (rRNA)

There are a variety of other forms of RNA involved in post-transcriptional modification, DNA replication and gene regulation within cells, as well as applications such as ribozymes, antisense RNA and small interfering RNA. Some viruses use RNA as their only nucleic acid, and others perform odd interactions with host cell DNA.

There is a school of thought that early life depended more on RNA to perform functions nowadays performed by proteins, and that in evolution DNA took over as a more stable archiving medium.

Nucleic acids are polymers of nucleotides

Each nucleotide is formed from a pentose (5-carbon) sugar, a nitrogen-containing organic base and a phosphate group.


Codes for the 5 carbon atoms of the pentose sugar are shown in blue

There are 4 different forms of DNA nucleotides and 4 different forms of RNA nucleotides, depending on the bases.

In DNA the pentose sugar is deoxyribose, and the bases are either adenine, cytosine, guanine or thymine. These are often abbreviated to A,C,G and T.

In RNA the pentose sugar is ribose, and the bases are either adenine, cytosine, guanine or uracil. These are often abbreviated to A,C,G and U.

Two classes of bases

Nitrogen displayed here in blue
Purines consist of 2 rings:
adenine
guanine



These 2-D images are taken from
3-D interactive files on this website.
DNA bases
RNA bases

Ribose and deoxyribose - possible bonding sites

C₅H₁₀O₅      and       C₅H₁₀O₄



Carbon numbers are shown without ' - prime

Hydroxyl (-OH) groups are the basis for bonds with other groups, formed by condensation reactions:
C1 to the organic base, C5 to the phosphate group.
And C3 bonds with phosphate on the next nucleotide (see below).
DNA does not have an -OH group at C2, which increases its long-term chemical stability
( -OH can make the C3 phosphate bond susceptible to alkaline hydrolysis)

The O shown in red spans between C1 and C4, forming an ether linkage.

Why uracil in RNA, but thymine in DNA?

Thymine is the same as uracil, but with a methyl group off to one side. See (and mouseover) diagram below

It has been suggested that this modification is more suited to DNA's role as a long-term store of information in that error-checking enzymes have evolved to bypass this base (thymine) as they screen for bases which might result from chemical changes which could result in mutations.

In particular, cytosine could become deaminated (and pick up a >O group). This would result in a uracil which would cause problems in DNA.

Interestingly, the bases form a flat section across the middle of the DNA molecule, but thymine's methyl group is the only section that projects somewhat from this.

Nucleotides join to form longer molecules

Two nucleotides can join together by forming another covalent bond between a phosphate group and carbon 3' on the next pentose sugar.

This is then called a phosphodiester bond, and it is quite a strong linkage but it is flexible and can rotate somewhat so the strand can become curved.

A polynucleotide is formed when this process is repeated many times.

As a result, the backbone of DNA and RNA is made up from alternating sugar and phosphate groups which are not easily broken apart.

The 3' and 5' labels are important in identifying the ends of nucleic acid strands, and showing the direction of propagation. This process only works in one direction, adding nucleotides to the 3' end of the developing polynucleotide chain.

In fact the 3' ends of DNA and RNA molecules have hydroxyl groups (-OH), whereas all the other nucleotides have phosphate groups attached at the 3' position.

The diagram at the right could be a short section of RNA, or a single strand of DNA.
Of course DNA has deoxyribose, and thymine not uracil.

Nucleotide nomenclature

The names of, or abbreviations for, the 5 (nitrogenous organic) bases in nucleic acids are generally quite well known.

Adenine A
Cytosine C
Guanine G
Thymine T
Uracil U


A nucleoside normally consists of a nitrogenous base section bonded to a pentose sugar.
These are given slightly different names:

Adenosine
Cytidine
Guanosine
Thymidine
Uridine

And a nucleotide consists of a nucleoside attached to a (single) phosphate group.

Adenosine monophosphate
Cytidine monophosphate
Guanosine monophosphate
Thymidine monophosphate
Uridine monophosphate

These could be written as

AMP, CMP, GMP, UMP for the RNA versions - ribonucleotides
( dAMP, dCMP, dGMP, dTMP, for the DNA versions - deoxyribonucleotides)

But some have more than one phosphate group:
ATP , ADP - adenosine triphosphate and diphosphate (and also GTP and GDP) are well known for their role in energy transfer in respiration and metabolic reactions in general, and UTP in glycogen synthesis

A DNA molecule is composed of two long polynucleotide chains

The two polynucleotide chains, running in different directions, are held together by hydrogen bonds between base pairs across the middle.

This base pairing is based on the complementary shapes of the exposed sections of the bases, and the number of hydrogen bonds that can be formed (2 between Adenine and Thymine, 3 between Cytosine and Guanine).

This gives specificity to the pairing of A with T (and obviously T with A) as well as C with G (or G with C). No alternative pairings are possible.

These two strands become gently twisted into a double helix.
←

Each strand can function as a template for re-forming the other, which is a key aspect of DNA replication before cells divide using mitosis or meiosis.
The DNA double helix
The sugar-phosphate backbone has been stylised into a cartoon
The flatness of the bases is very obvious

This 2-D image is taken from a 3-D interactive file on this website.
DNA structure

Pairings of nucleotides in DNA

Nitrogen displayed here in blue



Adenosine phosphate (left) forms 2 hydrogen bonds with thymidine phosphate (right)
Mouseover to highlight thymine's methyl group, which is not found in uracil (in RNA)



Guanidine phosphate (left) forms 3 hydrogen bonds with cytidine phosphate (right)

These 2-D images are taken from 3-D interactive files on this website.
DNA nucleotides adenosine phosphate and thymidine phosphate
DNA nucleotides cytidine phosphate and guanosine phosphate

An RNA molecule is comparatively short

An RNA molecule is a relatively short chain of nucleotides, often just a few hundred bases long.

It is also single stranded, although some sections of it may coil back on itself so that it looks double stranded. In these regions it can form base pairing with itself, although this is not as regular as in DNA.

Some viruses are exceptions to the double stranded DNA, single stranded RNA concept:

Click to see/ hide more information:

Single-stranded (ss) DNA viruses include: Protoparvovirus

RNA viruses can be divided into double-stranded, and positive and negative single stranded forms.

Double-stranded (ds) RNA viruses include:
Rotavirus - the most common cause of acute gastroenteritis in infants and young children worldwide Bluetongue virus (BTV): causes bluetongue disease - a non-contagious, insect-borne, viral disease of ruminants, mainly sheep

Positive stranded ('sense strand') single-stranded RNA is capable of being directly translated into protein, in the same way that ordinary cellular messenger RNA operates.
Examples of positive-sense single-stranded RNA (ssRNA) viruses: poliovirus (picornavirus), Zika virus

Negative stranded ('antisense strand') single-stranded RNA is not capable of being directly translated into protein, and has to be transcribed as soon as the virus enters the host in order to carry out viral replication. As a result, a viral-specific RNA polymerase is packaged in the virion, ready for transcription after virus entry.
Examples of negative-strand RNA viruses include influenza virus, measles viruses, rabies virus and Ebolavirus.

Retroviruses have genes encoded in RNA instead of DNA, and this needs to be reverse-transcribed into DNA by an enzyme called reverse transcriptase before it can be copied in the usual way. This is called retro in that it reverses the 'central dogma of molecular biology': DNA makes RNA makes protein. Examples of retrovirus: HIV - human immunodeficiency virus - which has the potential to cause AIDS - Acquired Immune Deficiency Syndrome. Other human retroviruses include HTLV-1 - the human T-cell lymphotropic virus 1, associated with certain T-cell leukaemias and lymphomas.

Click to hide the above

Mathematical certainties?

Different species have different amounts of the various bases in their cells.

In fact it was the discovery that the molecular make-up of DNA was not uniform that caused scientists to concentrate on its possible role as genetic material.
Some say that the relative simplicity of DNA led many scientists to doubt that it carried the genetic code.

Getting things in proportion

The ratios of A:T and G:C (and purines:pyrimidines) in normal double-stranded DNA in cells are always 1:1.

And (A+T+G+C) = 100%, so A+G is 50%, as is A+C, and T+G, as well as T+C.

This is also true for each of the DNA strands.

This information (in a slightly approximate form) was presented by Erwin Chargaff in the late 1940's, and it pre-dates the work of Watson and Crick in determining the structure of DNA.

Chargaff was interested in sea urchins, which can presumably be easily persuaded to produce gametes.

Comprehension test

It is possible to use incomplete information about the frequency of bases on DNA strands to find the frequency of others.

Organism	Percentage of each base
	Adenine	Guanine	Cytosine	Thymine
Sea urchin Echinoidea	32.5	17.5	17.5	32.5
Grasshopper Orthoptera	29.3	20.7	20.7	29.3
Octopus Octopus sp	32.4	17.6	17.6	32.4
Chicken Gallus sp	28.0	22.0	22.0	28.0
φX174 (PhiX174) bacteriophage virus	24.0	23.3	21.5	31.2

(Slightly modified) data from Erwin Chargaff

Mental arithmetic

Calculate the missing figures for Octopus DNA and mouseover the table to see if you are right.

You can even do this if you only know one value. Do the same for chicken DNA.


The bacteriophage virus has single-stranded DNA as its genetic material.
Using evidence from the table, explain why this DNA is single-stranded.

> percentages of A and T , also C and G (complementary bases) not equal / different values for each base

> therefore no 1:1 base-pairing (so single strand only)