The non coding genome: Finding jewel in the “Junk DNA”

The dictionary of science is filled with catchy yet misleading terms. For example The “god particle” has nothing to do with god. Genes cannot really be “selfish”, and when astronomers talk about “metals”, they usually mean something else entirely. Now, we have to add “junk DNA” to the list of scientific misnomers.

Only a small part of our DNA contains genes that encodes for the proteins that go on to build who we are. So why do we have the rest of our genome?

Over many decades, the “junk” has been broadly used to refer to non-coding sequences in our DNA that appear to lack any function. It was first used in the 1960s to suggest that the majority of our DNA may be expendable. The term “junk DNA” has become very popular, although it has deterred some from studying it. Who would seriously apply for funding to investigate junk?

In the last few decade, new methods to identify the DNA that is transcribed into RNA (a chemical cousin of DNA) have suggested that about 80% of DNA may serve some purpose. Many thousands of new hypothetical genes that encode only RNA, but not proteins, have been discovered. Some of these strands of RNA are indeed involved in the regulation of genes, such as deciding when to switch them on and when to switch them off.

The result of these findings made some question the very existence of junk DNA. Yet others argued that the variable size of many genomes filled with largely repetitive sequences can’t explain the complexity of organisms and that there has to be a chunk of DNA with no function. Why does an onion need a genome that is about five times larger than ours?

It has been clear for a long time that there is a lot more to DNA than just genes. Indeed, one of the great scientific surprises in recent decades has been the discovery that the human genome is surprisingly deprived of actual genes. When the first draft of it was published in the summer of 2001, it did not describe the 100,000 or more genes that most biologists assumed we had, but fewer than 20,000 making Homo sapiens not much more well-endowed genetically than a fruit fly or even a lump of yeast.

The Dynamic Genome

Even though we are now certain that many non-coding DNA sequences help in protecting and stabilising the genome, regulating genes, differentiating cells and forming tissue, organ development from birth to death, differences between people, their variable response to drugs and other environmental cues, and predisposition to a growing number of human diseases, we do not know how much junk is in our DNA. But can we find out?

To appreciate the origin and extent of junk DNA in our cells, we need to understand how it got evolved. One of the most critical events in evolution : the duplication of genes, or their coding parts (called exons) – give the cells and organisms a chance to test new function without endangering their viability or fitness. As duplicated genes, exons or non-coding DNA diverge through errors in replication or DNA repair over many years, the functions of either new or ancestral copies may change. The cell may select sequences underlying new, similar or even opposite functions, leaving either copy in the genomic scrapyard. This does not mean, however, that the discarded DNA segments are no longer useful to the cell.

Genomes are extremely dynamic entities: new functional elements continuously appear and old ones may become extinct. This can be illustrated by repetitive elements named “Alus” that are found in primate genomes, that have accumulated a total of over one million copies and occupy about 11% of human DNA. Alus are often transcribed as RNA and are an important source of new coding parts, gene regulatory elements and protein diversity, especially in highly organised tissues such as the brain. They had a key role in human development and most likely contribute to our distinction from other primates. They might also help evolution get better over time, yet these and other interspersed repeats were initially dismissed as junk.

 Are we ready to edit the human genome?

If junk DNA could alter the function of a cell at any time and we can’t define it, how can we safely edit our genomes? Genome editing technologies such as CRISPR are powerful tools to manipulate both coding and non-coding DNA and study their function.

But we cannot overlook the possiblities to how the junk DNA would not harm the expressed genes . They may have inadvertent consequences for the cell or the organism that may become apparent only later in life, such as mental illness,cancer or even infertility into future generations.

It’s deeply rooted in our nature to fear or dismiss what we don’t fully understand. Although we cannot predict which DNA segment may become functional today and which tomorrow, we are now equipped with tools including genome editing to examine the function of non-coding DNA in greater detail in the coming years.

We should support activities which improves this understanding and avoid those that might damage what we may never be able to repair or create again, namely, the irreplaceable heritage of well over one billion years of evolution, including the human genome.


Orignal article was published in The Conversation

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