Junk DNA

In evolutionary biology and molecular biology, junk DNA is a provisional label for the portions of the DNA sequence of a chromosome or a genome for which no function has been identified.

The term was introduced in 1972 by Susumu Ohno, but is somewhat outdated (as of 2008), being used mainly in popular science and in a colloquial way in scientific publications. If DNA does not seem to have a function now it may have had a function in the past or may yet have a function in future.

Size of junk DNA

About 95% of the human genome has at one time been designated as "junk", including most sequences within introns and most intergenic DNA. While much of this sequence may be an evolutionary artifact that serves no present-day purpose, some junk DNA may function in ways that are not currently understood. Moreover, the conservation of some junk DNA over many millions of years of evolution may imply an essential function.

Some consider the "junk" label as something of a misnomer, but others consider it appropriate as junk is stored away for possible new uses, rather than thrown out; others prefer the term "noncoding DNA" (although junk DNA often includes transposons that encode proteins with no clear value to their host genome). About 80% of the bases in the human genome may be transcribed, but transcription does not necessarily imply function.

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, if any, of the remainder remains under investigation. Most of it can be identified as repetitive elements that have no known biological function for their host (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". 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 nonfunctional. However, it remains a possibility that there is some function that the experiments performed on the mice were merely insufficient to detect. This can also be evidence for reconstructing ancestral lineages.

While overall genome size, and by extension the amount of junk DNA, are correlated to organism complexity, there are many exceptions. For example, 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 the junk DNA. This puzzle is known as the C-value enigma or, more conventionally, the C-value paradox.

Types of junk DNA

• Pseudogenes - Some chromosomal regions are 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.
• Retrotransposons - 8% of the human genome has been shown to be formed by retrotransposons of Human Endogenous Retroviruses (HERVs), although as much as 25% is recognisably formed of retrotransposons. This is a lower limit on how much of the genome is retrotransposons because older remains might not be recognizable having accumulated too many mutations. New research suggests that genome size variation in at least two kinds of plants is mostly because of retrotransposons.

Hypotheses of origin and function

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

• 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 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 of information it contains is irrelevant.
• Some portions of junk DNA could serve presently unknown regulatory functions, controlling the expression of certain genes during the development of an organism from embryo to adult, and/or development of certain organs/organelles.
• Regulatory layers in some junk DNA, such as through non-coding RNAs, may contain important genetic programming.
• According to a comparative study of over 300 prokaryotic and over 30 eukaryotic genomes , eukaryotes appear to require a minimum amount of non-coding DNA. This minimum amount can be predicted using a growth model for regulatory genetic networks, implying that it is required for regulatory purposes. In humans the predicted minimum is about 5% of the total genome.

Evolutionary conservation of junk DNA

Comparative genomics is a promising direction in studying the function of junk DNA. Biologically functional sequences 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 their divergence. Since known functional sequence comprises less than 2% of the human genome, there may be more junk DNA in the human genome than there is 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.

Present results concerning evolutionarily conserved human junk DNA are expressed in 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. Conversely, there are some questions about the hypothesis that conserved sequences all must function .

Replication of junk DNA each time a cell divides may waste energy. Organisms with less junk DNA may therefore have a selective advantage, and natural selection would tend to eliminate it. There are several possible explanations for why it has not been eliminated: (1) The energy required to replicate even large amounts of junk DNA may be 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); (2) Junk DNA may provide a reservoir of potentially useful sequences or a protective buffer against harmful genetic damage or mutations; and (3) Junk DNA may accumulate faster than natural selection can eliminate it. In animals, the energy required for DNA synthesis is trivial compared to the metabolic energy invested in the movement of muscles.

Functions for some subsets of junk DNA

Over the years evidence is accumulating that more and more of the so-called junk DNA might have a function, even if we do not know yet what that function is.

Different studies remark on the importance of junk DNA for social behavior in rodents (and, possibly humans) , regulation of gene expression and promotion of genetic diversity , evolution of sequences (for example, an antifreeze-protein gene in a species of fish ), as a source of microRNAs , and hosting DNA segments called LINE-1 capable of repairing broken strands of DNA.

In a publication in the August 14th issue of PLoS Genetics, USC researchers identified non-coding regions on chromosome 8 (8q24) that appear to predict risk of developing prostate cancer.

Scientists from Japan and Singapore artificially made proteins from the "junk" DNA of E.coli. One of the artificially synthesized proteins killed the cell itself. This is the first evidence that junk DNA, the so-called "dark matter" of genome, may have enormous information waiting to be uncovered.

It is noted that the fact that some non-coding DNA has a purpose does not establish that all non-coding DNA has a purpose. In addition, sections of DNA can be randomized, cut, or added to with no apparent effect on the organism in question. [14]

See also

• Atavism
• Alu repeat
• Eukaryotic chromosome fine structure
• Function (biology)
• Genealogical DNA test
• Intron
• Repeated sequence (DNA)
• Retrotransposon
• Satellite DNA
• Selfish DNA

Further reading

• Gibbs W.W. (2003) "The unseen genome: gems among the junk", Scientific American, 289(5): 46-53. (A review, written for non-specialists, of recent discoveries of function within junk DNA.)