Non-coding DNA: More than Genetic ‘Junk’

The Human Genome Project has enabled the development of important advances in the area of genetics. One of the most relevant milestones was the discovery that, of a person’s total genetic information, only 1 to 2% is responsible for coding for protein synthesis. Since the remaining 98% does not contain coding information, it has long been colloquially known as “junk DNA”; however, more and more is being learned about the importance of this region of DNA in the functioning of the organism.

We will try to address what is non-coding DNA and what types of sequences we find.

What do we mean by non-coding DNA?

Although there are different types of sequences within the genome, we generally distinguish between coding regions and non-coding regions, colloquially known as “junk DNA”. The coding regions are part of the sequences that during the transcription process become protein coding. The study of DNA has historically focused on coding regions since they account for 98% of known genetic variants related to hereditary diseases, but there is increasing evidence showing the relevance of non-coding sequences.

We can distinguish the following types of non-coding DNA sequences:

• Pseudogenes: Sequences that structurally resemble known genes, but do not code for proteins.
• Telomeres: Regions of repetitive DNA located at the ends of chromosomes that protect them, increasing their stability. Telomeres shorten with each cell division.
• Repeated sequences, transposons and viral elements: elements with the ability to move to different regions of the genome autonomously.
• Cis- and trans-regulatory elements: sequences that regulate transcription of a nearby or distant gene.
• Introns:  Sequences located between exons that are transcribed into a precursor sequence, but are ultimately deleted in the final mature messenger RNA transcript.

As we have mentioned in other articles, genes are the basic unit of the genome and are themselves made up of coding and non-coding DNA. The coding regions are called exons while the regions between one exon and another are called introns. The exome accounts for 1-2% of the genome and introns make up 24% of the DNA. Although intronic regions are non-coding, they include the 5′-UTRs (untranslated regions) or 3′-UTRs, regulatory regions of great importance in the transcription process. In addition, between one gene and another are the intergenic regions, also made up of non-coding DNA.

Introns and non-coding regions

Now, if introns and non-coding regions are not converted into proteins, what is their function? Until recently, the importance of these regions was not known, so many of their functions are still under study. Currently, it is known that these types of sequences have important functions:

• Structural function: this type of DNA is involved in the compaction of chromosomes and in the organization of centromeres, the narrow X-shaped point of the chromosome pair.
• Regulatory function: This type of DNA associates with proteins to form chromatin, a molecular structure that controls transcription. Have you ever wondered why cells with the same genetic information form a neuron or a liver cell? Well, the condensation of chromatin (heterochromatin and euchromatin) allows to control the expression of the genes that are needed in each type of cell and to silence the rest. In addition, in these regions there are regulatory sequences that provide binding sites for transcriptional control or sometimes exert their regulatory function through the formation of non-coding RNA.
• Protective function: One of the most important functions is to protect the DNA from degradation or damage during the copying of the genetic material.

Importance of junk DNA or non-coding DNA

Our genetic material can present mutations that can cause disease. Different studies have shown that in addition to mutations affecting coding regions, variants in non-coding regions of DNA can also be related to diseases.

In many pathologies of genetic origin there are variants described in non-coding regions, such as in some types of cancer or the non-syndromic Pierre Robin sequence, caused by mutations or deletions in regions close to the SOX9 gene.

Another example of how variants in junk DNA can influence health is found in polygenic risk testing, or PRS. These tests study thousands or millions of common variants spread throughout the genome, both in coding and non-coding regions, which alone have a small impact on health, but taken together can detect a hitherto undetected type of risk. Some of the pathologies that present polygenic risk scores validated in the literature are breast cancer, prostate cancer, coronary artery disease or type 2 diabetes.

ENCODE Project

The term “junk DNA” is increasingly being discarded thanks to the results of multiple scientific studies.  The use of this concept is beginning to decline with the first results of the ENCODE project. This project seeks to construct a complete list of all the functional elements that exist in the human genome, which act both at the level of proteins and at the level of RNA and regulatory elements, the circumstances that cause genes to be activated and transcribed into proteins. During this project, some of the essential functions of non-coding DNA, such as regulating the activity of our genes, have been discovered.

Thanks to advances in scientific knowledge, “junk DNA” came to be called non-coding DNA because, although it does not directly synthesize proteins, it has an essential function in the organism. In fact, different studies have also determined that there is generally a positive correlation between the complexity of the organism and the amount of non-coding DNA found in its genome.

At Veritas, we are committed to proactive health care, offering both preventive and diagnostic tests to improve people’s health through genetics. Whole genome sequencing and polygenic risk tests are some of the preventive tests at the service of doctor and patient to implement preventive medicine as part of health care.