THE USE OF NON- CODING DNA IN THE HUMAN GENOME

The regions of the human genome that do not have any apparent protein coding function are known
as non- coding DNA. Initially, these non- coding parts of the genome were dismissed by the
scientific fraternity as useless and thus termed as junk DNA. However, this view has been
changed largely over the years. Perhaps the most important reason for this change is the sheer
volume of non- coding DNA that is present in our cells. After the completion of the human genome
project it was made clear that about 98% of the DNA in a human cell has no apparent protein
coding function. The importance of the non- coding DNA in our cells can be assessed by the fact
that the only genomic features that increased in number as animals became more complicated were
the regions of non- coding or junk DNA. This observation points out that there is a chance that the
key to evolutionary complexity lies with junk DNA.

It is becoming evident that non- coding DNA has many different functions. A portion of the non-
coding DNA is responsible for forming specific structures in the chromosomes and thereby
preventing our DNA from untying and getting damaged. Two of such important structures formed
by the non- coding DNA are the centromeres and the telomeres. Other non- coding regions function
as insulations which help in restricting gene expression to specific regions of chromosomes.
Telomeres are specific structures formed by a large chunk of non- coding DNA that is present at
the end of each of our chromosomes. The length of the telomere gets shortened with each round
of replication. In absence of telomeres, the ends of the chromosomes will not be protected and they
will become susceptible to exonuclease action or will get attached to free and sticky ends of other
chromosomes. Another specialized structure, the centromeres is also extremely important for
proper cell division. Centromeres are specific structures that are formed within the chromosomes.
These are the structures where the spindle fibers bind and pull individual chromosomes to the two
opposite poles of the cell during cell division. Centromeres are formed of non- coding DNA that
are tightly packed and bound to a specific protein called CENP-A.

However, a huge amount of the non- coding DNA present in humans is not simply structural.
Though these regions do not code for any particular protein, they code for RNAs that are essential
for gene regulation and other important cellular functions. In addition to the non- coding DNA
which is present in the centre and the terminals of the chromosomes, each functional, protein
coding gene also has chunks of non- coding DNA inside them. These regions which do not
ultimately appear in the protein coding mRNA are known as introns. These regions are critical for
regulating how the messenger RNAs are used by the cells, and create yet another level of control,
thereby regulating the amount of protein that is finally produced by the gene. Another possible
role for the non- coding regions of the genome can be explained by the insulation theory. The
protein coding regions of the genome are extremely important. Any mutations or replication errors
in these regions can have deleterious effects as it may lead to production of a faulty protein which
can ultimately result in cell death. Having large chunks of non- coding DNA might help in
absorbing the mutations that are caused by evolutionary pressure.

Another important function served by the non- coding regions is regulation of gene expression.
One of the best examples for this phenomenon is X inactivation. Females have two copies of the
X chromosome; however, the males only contain one X chromosome. If both the X chromosomes
in females were indeed active, it would mean that females would have twice the amount of proteins
than males. However, one of the X chromosomes in females is inactivated in a process called
dosage compensation. This is achieved by a functional RNA molecule that does not code for any
protein. This RNA molecule is called the Xist RNA. Xist RNA covers the entire X chromosome
that needs to be inactivated. The human genome expresses many RNA molecules similar to Xist
that have important cellular functions. Other such important non- coding RNAs are the tRNA and
the rRNAs, both of which are extremely important for the process of translation. The tRNA
molecules act as the adapters between messenger RNA and the final protein. This ensures the
amino acids are added in the right order to create proper protein molecules. When two amino acids
are held next to each other at the ribosome, the rRNA can carry out chemical reactions to form
proteins.

In addition to the regulation brought about the regulatory RNAs like Xist, switching on a gene is
dependent on a region of non- coding DNA called the promoter. There is a promoter at the
beginning of every protein- coding gene. Specific transcription factors bind to the promoter
sequence and recruit RNA polymerase, thereby switching on transcription. Another such
regulatory DNA element is the enhancer.