Beyond AGCT: DNA’s two “new” bases

Sakina Bano Mendha
15 July 2015

Above: Image © istockphoto.com/alex-mit

Deoxyribonucleic acid (DNA) is the main component of the genetic material that contains your hereditary information. One of the first things you learned about DNA might have been that is has four bases: adenine, guanine, cytosine and thymine. However, a few years ago, a fifth base, called methyl cytosine, was discovered. More recently, a scientific article announced the discovery of a sixth base, called methyl adenine. Whereas the “old” bases and the bonds between them affect the sequence of your DNA, the “new” ones relate to epigenetics—how genes are turned “on” and “off”.

AGCT

Did you know? The base that differentiates RNA from DNA is Uracil, which replaces the thymine.DNA is composed of two strands, which are connected to each other through hydrogen bonding (pairing) among bases. Guanine is bonded to cytosine by three hydrogen bonds, whereas thymine and adenine are bonded together by two hydrogen bonds. Thymine and cytosine are pyrimidines, which means that the atoms and electrons are bonded together in a single ring structure. Adenine and guanine are purines, meaning their structure involves two rings.

Hydrogen bonds are weak and DNA can be denatured or strands can be separated by breaking the bonds with heat or enzymes. Enzymes are biological catalysts. This means they speed up chemical reactions that occur in living organisms without undergoing any permanent changes in their own structure. A certain amount of energy is needed for chemical reactions to occur (activation energy) and enzymes provide a pathway for the reaction to occur at a relatively low activation energy. This increases the likelihood the reaction will occur and consequently speed up the rate of the reaction. Enzymes that separate strands of DNA are called helicases.

DNA base pairs play an important role in the human genome. Their sequence determines your genetic information, so any unexpected variations these bonds cause genetic mutations that can affect your phenotype (your physical characteristics). In some cases, these mutations can cause specific diseases. For example, sickle cell anaemia is the result of thymine bonding to guanine instead of adenine, causing the production of valine (GTG) instead of glutamic acid (GAG). This change in the DNA affects the shape of the haemoglobin cell in such a way that why it is no longer able to carry oxygen to tissues via the blood.

Methyl cytosine and methyl adenine

More recently, scientists have identified two new bases of DNA. Unlike the fours bases involved in base pairing, these new bases play a role in epigenetics. That means they affect changes in gene expression through processes such as DNA methylation and histone modifications, processes that are independent of the genome’s DNA sequence. First, in the early 1990s, methylcytosine was recognized as the fifth base of DNA. Derived from cytosine, methylcytosine can cause have been linked to certain forms of cancer, autoimmune disease, and a range of birth defects.

Did you know? DNA strands are separated and transcribed using enzymes to form an RNA strand. RNA is then translated to form proteins using specific organelles.In 2015, the scientific journal Cell published three separate studies that all provided strong evidence for the existence of a sixth base called methyladenine. It plays a role similar to methylcytosine in gene expression and physical development in certain eukaryotes, such as algae, worms, and flies. Eukaryotes are organisms, including humans, with complex cells that contain specialized organelles. The genome on which the research was conducted would therefore be relatively similar to yours, which suggests that methyladenine could play a similar role in the human genome.

Researcher Manel Esteller explains how, “It was known for years that bacteria, evolutionarily very distant living organisms of us, had methyladenine in its genome with a protective function against the insertion of genetic material from other organisms. But it was believed that this was a phenomenon of primitive cells and it was very static." However, Dr. Esteller’s research and that of others points to methyladenine playing an important genetic role in much more complex organisms, including humans.

The next challenge for biomedical researchers is to confirm the presence of methyladenine in human DNA and discover its specific role. Methyladenine is relatively uncommon in mammalian DNA, and even when it is present in a genome it can still be difficult to pinpoint its exact location, which is necessary to understand its exact function. However, researchers are hopeful that recent advances in biochemical techniques will help them better detect where and when methyladenosine is present in DNA, opening up exciting new areas of study.

Learn more!

Researchers report possible discovery of sixth DNA base, methyl-adenine (2015)
Phys.org

An Adenine Code for DNA: A Second Life for N6-Methyladenine (2015)
H. Heyn & M. Esteller, Cell 161
Link to abstract. Registration or subscription required to view full text.

News report and scientific article on the identification of methyl-adenine as the sixth base of DNA.

Identification of a Selective Polymerase Enables Detection of N6-methyladenosine in RNA (2013)
E. M. Harcourt, T. Ehrenschwender, P. J. Batista, H. Y. Chang & E. T. Kool, Journal of the American Chemical Society 135

Focus on molecules: 5-methylcytosine, a possible epigenetic link between ageing and ocular disease (2012)
K. P. Mitton & A. E. Guzman, Experimental Eye Research 96
Link to outline. Registration or subscription required to view full text.

Scientific article on the epigenetic role played by methylcytosine and methyl-adenine.

Sakina Bano Mendha

I am a Student currently enrolled doing my biology undergraduate studies from Montreal, Canada. I like playing badminton and doing Calligraphy. Skills: Public speaking, writing, research, teamwork. 



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