Junk DNA

In molecular biology, "junk" DNA is a collective label for the portions of the DNA sequence of a chromosome or a genome for which no function has yet been identified. About 98.5% of the human genome has been designated as "junk", including most sequences within introns and most intergenic DNA.

While much of this sequence is probably an evolutionary artifact that serves no present-day purpose, some may function in ways that are not currently understood. In fact, recent studies have suggested functions for certain portions of what has been called junk DNA. Moreover, the conservation of some "junk" DNA over many millions of years of evolution may imply an essential function. The "junk" label is therefore recognized as something of a misnomer, and many prefer the more neutral term "noncoding DNA".

Broadly, the science of functional genomics has developed widely accepted techniques to characterize protein-coding genes, RNA genes, and regulatory regions. In the genomes of most plants and animals, however, these together constitute only a small percentage of genomic DNA (less than 2% in the case of humans). The function of the remainder, if any, remains under investigation. Most of it can be identified as repetitive elements that have no known biological function (although they are useful to geneticists for analyzing lineage and phylogeny). Still, a large amount of sequence in these genomes falls under no existing classification other than "junk".

Overall genome size, and by extension the amount of junk DNA, appears to have little relationship to organism complexity: the genome of the unicellular Amoeba dubia has been reported to contain more than 200 times the amount of DNA in humans. The pufferfish Takifugu rubripes genome is only about one tenth the size of the human genome, yet seems to have a comparable number of genes. Most of the difference appears to lie in what is now known only as junk DNA. This puzzle is known as the "C-value enigma" or, more conventionally, the "C-value paradox".

Hypotheses of Origin and Function

There are many hypotheses, none conclusively established, for how junk DNA arose and why it persists in the genome:

These chromosomal regions could be composed of the now-defunct remains of ancient genes, known as pseudogenes, which were once functional copies of genes but have since lost their protein-coding ability (and, presumably, their biological function). After non-functionalization, pseudogenes are free to acquire genetic noise in the form of random mutations.

8% of the junk DNA has been shown to be formed by retrotransposons of Human Endogenous Retroviruses (HERVs), although as much as 25% is recognizably formed of retrotransposons.

Junk DNA may act as a protective buffer against genetic damage and harmful mutations. For example, a high proportion of nonfunctional sequence makes it unlikely that a functional element will be destroyed in a chromosomal crossover event, possibly making a species more tolerant to this important mechanism of genetic recombination.

Junk DNA might provide a reservoir of sequences from which potentially advantageous new genes can emerge. In this way, it may be an important genetic basis for evolution.

Some junk DNA could simply be spacer material that allows enzyme complexes to form around functional elements more easily. In this way, the junk DNA could serve an important function even though the actual sequence information it contains is irrelevant.

Some portions of junk DNA could serve presently unknown regulatory functions, controlling the expression of certain genes and/or the development of an organism from embryo to adult.Junk DNA may serve other, unknown purposes. For example, some non-coding RNAs have been discovered in what had been considered junk.

Junk DNA may have no function. For example, recent experiments removed 1% of the mouse genome and were unable to detect any effect on the phenotype. This result suggests that the DNA is, in fact, non-functional. However, it remains a possibility that there is some function that the experiments performed on the mice were merely insufficient to detect.

Evolutionary Conservation of Junk DNA

Comparative genomics is a promising direction in studying the function of junk DNA. Biologically functional sequences, as the theory goes, tend to undergo mutation at a slower rate than nonfunctional sequence, since mutations in these sequences are likely to be selected against. For example, the coding sequence of a human protein-coding gene is typically about 80% identical to its mouse ortholog, while their genomes as a whole are much more widely diverged. Analyzing the patterns of conservation between the genomes of different species can suggest which sequences are functional, or at least which functional sequences are shared by those species. Functional elements stand out in such analyses as having diverged less than the surrounding sequence.

Comparative studies of several mammalian genomes suggest that approximately 5% of the human genome has evolved under purifying selection since the divergence of the mammals. Since known functional sequence comprises less than 2% of the human genome, it appears that there may be more functional "junk" DNA in the human genome than there is known functional sequence.

A surprising recent finding was the discovery of nearly 500 ultraconserved elements, which are shared at extraordinarily high fidelity among the available vertebrate genomes, in what had previously been designated as junk DNA. The function of these sequences is currently under intense scrutiny, and there are preliminary indications that some may play a regulatory role in vertebrate development from embryo to adult.

It must be noted that all present results concerning evolutionarily conserved human "junk" DNA are expressed in highly preliminary, probabilistic terms, since only a handful of related genomes are available. As more vertebrate, and especially mammalian, genomes are sequenced, scientists will develop a clearer picture of this important class of sequence. However, it is always possible, though highly unlikely, that there are significant quantities of functional human DNA that are not shared among these species, and which would thus not be revealed by these studies.

On a theoretical note, it is often observed that the presence of high proportions of truly nonfunctional "junk" DNA would seem to defy evolutionary logic. Replication of such a large amount of useless information each time a cell divides would waste energy.

Organisms with less nonfunctional DNA would thus enjoy a selective advantage, and over an evolutionary time scale, nonfunctional DNA would tend to be eliminated. If one assumes that most junk DNA is indeed nonfunctional, then there are several hypotheses for why it has not been eliminated by evolution:

The energy required to replicate even large amounts of nonfunctional DNA is in fact relatively insignificant on the cellular or organismal scale, so no selective pressure results (selection coefficients less than one over the population size are effectively neutral);

The aforementioned possible advantage of having extra DNA as a reservoir of potentially useful sequences; and

Retrotransposon insertions of nonfunctional sequence occurring faster than evolution can eliminate it. These are all hypotheses for which the time scales involved in evolution may make it difficult for humans to investigate rigorously. Read more

In pseudoscience Junk DNA may refer to information implanted
by aliens, to expedite the evolution of human design.

In the News ...

Our Genomes Are Full of Junk DNA That Could Be Way More Important Than We Realized   Science Alert - February 27, 2023
Of the roughly three billion base pairs making up the human genome, only around 2 percent encodes proteins, leaving the remaining 98 percent with less obvious functions. Dismissed by some as useless 'junk DNA', its origins, effects, and potential purpose in the evolution of life has attracted the attention of biologists ever since it was first noticed cluttering up our chromosomes in the 1960s.

'Junk RNA' molecule found to play key role in cellular response to stress   PhysOrg - December 15, 2016
A study from Massachusetts General Hospital (MGH) investigators has found a surprising role for what had been considered a nonfunctional "junk" RNA molecule: controlling the cellular response to stress. In their report in the Dec. 15 issue of Cell, the researchers describe finding that a highly specific interaction between two elements previously known to repress gene transcription - B2 RNA and EZH2, an enzyme previously known only to silence genes actually induces the expression of stress-response genes in mouse cells.

Brain Development Is Guided by Junk DNA That Isn't Really Junk   Science Daily - April 16, 2013
Specific DNA once dismissed as junk plays an important role in brain development and might be involved in several devastating neurological diseases, UC San Francisco scientists have found. While researchers have been busy exploring the roles of proteins encoded by the genes identified in various genome projects, most DNA is not in genes. This so-called junk DNA has largely been pushed aside and neglected in the wake of genomic gene discoveries, the UCSF scientists said.

Research team finds key to childhood brain disease lies in genetic junk   PhysOrg - March 13, 2012
As researchers come to understand better how the human genome is put together, they quite often stumble across what appear to be puzzles. One example of this is bits of the genome that appear to no longer serve a useful purpose. Such bits are referred to as junk genes. Some of the junk is dead genes while others are hopping genes that can move themselves to other parts of the genome, and some are what's left of hopping genes after they can no longer hop.

Junk DNA Mechanism That Prevents Two Species From Reproducing Discovered   Science Daily - October 27, 2009
Cornell researchers have discovered a genetic mechanism in fruit flies that prevents two closely related species from reproducing, a finding that offers clues to how species evolve. Cornell researchers report that rapidly evolving "junk" DNA may create incompatibilities between two related species, preventing them from reproducing.

'Junk' DNA now looks like powerful regulator, researcher finds   PhysOrg - April 23, 2007
Large swaths of garbled human DNA once dismissed as junk appear to contain some valuable sections, according to a new study by researchers at the Stanford University School of Medicine and the University of California-Santa Cruz. The scientists propose that this redeemed DNA plays a role in controlling when genes turn on and off.

Salvage prospect for 'junk' DNA   BBC - April 26, 2006
A mathematical analysis of the human genome suggests that so-called "junk DNA" might not be so useless after all. The term junk DNA refers to those portions of the genome which appear to have no specific purpose. But a team from IBM has identified patterns, or "motifs", that were found both in the junk areas of the genome and those which coded for proteins. The presence of the motifs in junk DNA suggests these portions of the genome may have an important functional role.

Scientists Uncover Clues To The Mystery Of 'Gene Deserts' Science Daily - December 9, 2004
Gene deserts are long stretches of DNA between genes that were once thought to have no biological function, and were dismissed as "junk DNA." As scientists probe deeper into the DNA's double helix, however, they are discovering that many of these "non-coding" segments actually play an important role in regulating gene activity.

'Junk' throws up precious secret DNA   BBC - May 12, 2004
Researchers inspecting the genetic code of rats, mice and humans were surprised to find they shared many identical chunks of apparently "junk" DNA. This implies the code is so vital that even 75 million years of evolution in these mammals could not tinker with it.