8.2 percent of our DNA is 'functional'

Jul 24, 2014

Only 8.2% of human DNA is likely to be doing something important – is 'functional' – say Oxford University researchers.

This figure is very different from one given in 2012, when some scientists involved in the ENCODE (Encyclopedia of DNA Elements) project stated that 80% of our genome has some biochemical function.

That claim has been controversial, with many in the field arguing that the biochemical definition of 'function' was too broad – that just because an activity on DNA occurs, it does not necessarily have a consequence; for functionality you need to demonstrate that an activity matters.

To reach their figure, the Oxford University group took advantage of the ability of evolution to discern which activities matter and which do not. They identified how much of our genome has avoided accumulating changes over 100 million years of mammalian evolution – a clear indication that this DNA matters, it has some important function that needs to be retained.

'This is in large part a matter of different definitions of what is "functional" DNA,' says joint senior author Professor Chris Pointing of the MRC Functional Genomics Unit at Oxford University. 'We don't think our figure is actually too different from what you would get looking at ENCODE's bank of data using the same definition for functional DNA.

'But this isn't just an academic argument about the nebulous word "function". These definitions matter. When sequencing the genomes of patients, if our DNA was largely functional, we'd need to pay attention to every mutation. In contrast, with only 8% being functional, we have to work out the 8% of the mutations detected that might be important. From a medical point of view, this is essential to interpreting the role of human genetic variation in disease.'

The researchers Chris Rands, Stephen Meader, Chris Ponting and Gerton Lunter report their findings in the journal PLOS Genetics. They were funded by the UK Medical Research Council and the Wellcome Trust.

The researchers used a computational approach to compare the complete DNA sequences of various mammals, from mice, guinea pigs and rabbits to dogs, horses and humans.

Dr Gerton Lunter from the Wellcome Trust Centre for Human Genetics at Oxford University, the other joint senior author, explained: 'Throughout the evolution of these species from their common ancestors, mutations arise in the DNA and natural selection counteracts these changes to keep useful DNA sequences intact.'

The scientists' idea was to look at where insertions and deletions of chunks of DNA appeared in the mammals' genomes. These could be expected to fall approximately randomly in the sequence – except where natural selection was acting to preserve functional DNA, where insertions and deletions would then lie further apart.

'We found that 8.2% of our is functional,' says Dr Lunter. 'We cannot tell where every bit of the 8.2% of functional DNA is in our genomes, but our approach is largely free from assumptions or hypotheses. For example, it is not dependent on what we know about the genome or what particular experiments are used to identify biological function.'

The rest of our genome is leftover evolutionary material, parts of the genome that have undergone losses or gains in the DNA code – often called 'junk' DNA.

'We tend to have the expectation that all of our DNA must be doing something. In reality, only a small part of it is,' says Dr Chris Rands, first author of the study and a former DPhil student in the MRC Functional Genomics Unit at Oxford University.

Not all of the 8.2% is equally important, the researchers explain.

A little over 1% of human DNA accounts for the proteins that carry out almost all of the critical biological processes in the body.

The other 7% is thought to be involved in the switching on and off of genes that encode proteins – at different times, in response to various factors, and in different parts of the body. These are the control and regulation elements, and there are various different types.

'The proteins produced are virtually the same in every cell in our body from when we are born to when we die,' says Dr Rands. 'Which of them are switched on, where in the body and at what point in time, needs to be controlled – and it is the 7% that is doing this job.'

In comparing the genomes of different species, the researchers found that while the protein-coding genes are very well conserved across all mammals, there is a higher turnover of DNA sequence in the regulatory regions as this sequence is lost and gained over time.

Mammals that are more closely related have a greater proportion of their functional DNA in common.

But only 2.2% of human DNA is functional and shared with mice, for example – because of the high turnover in the regulatory DNA regions over the 80 million years of evolutionary separation between the two species.

'Regulatory DNA evolves much more dynamically that we thought,' says Dr Lunter, 'but even so, most of the changes in the genome involve junk DNA and are irrelevant.'

He explains that although there is a lot of functional DNA that isn't shared between mice and humans, we can't yet tell what is novel and explains our differences as species, and which is just a different gene-switching system that achieves the same result.

Professor Ponting agrees: 'There appears to be a lot of redundancy in how our biological processes are controlled and kept in check. It's like having lots of different switches in a room to turn the lights on. Perhaps you could do without some switches on one wall or another, but it's still the same electrical circuit.'

He adds: 'The fact that we only have 2.2% of DNA in common with mice does not show that we are so different. We are not so special. Our fundamental biology is very similar. Every mammal has approximately the same amount of functional DNA, and approximately the same distribution of functional DNA that is highly important and less important. Biologically, humans are pretty ordinary in the scheme of things, I'm afraid.

'I'm definitely not of the opinion that mice are bad model organisms for animal research. This study really doesn't address that issue,' he notes.

Explore further: New functions for 'junk' DNA?

More information: PLoS ONE DOI: 10.1371/journal.pgen.1004525

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Scottingham
5 / 5 (6) Jul 24, 2014
For every article like this there are 5 more saying 'Turns out X actually isn't unused at all, but in fact very important'

What if this 'non-functional' DNA is necessary for enzymatic time delays or proper histone wrapping/encoding or something.
NeutronicallyRepulsive
5 / 5 (4) Jul 24, 2014
It's easy to test. Determine this for some test animal. Remove it and produce an "optimized" rat (or something) and we'll see. So far I'm skeptical. As Scottingham pointed out there can be some structural considerations or simply statistical ones.
JVK
1 / 5 (5) Jul 24, 2014
Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors. http://www.ncbi.n...24693349
Conclusion: "Olfaction and odor receptors provide a clear evolutionary trail that can be followed from unicellular organisms to insects to humans (Keller et al., 2007; Kohl, 2007; Villarreal, 2009; Vosshall, Wong, & Axel, 2000)."

Nutrient-dependent/pheromone-controlled adaptive evolution: a model. http://www.ncbi.n...24693353
Conclusion: "Minimally, this model can be compared to any other factual representations of epigenesis and epistasis for determination of the best scientific 'fit'."

The mouse-to-human model of nutrient-dependent pheromone-controlled ecological variation that leads to a base pair change and single amino acid substitution that differentiates cell types links the primacy of olfactory/pheromonal input to the percentage of the human genome that appears to be the most functional via ecological adaptations.
Hakan1997
not rated yet Jul 25, 2014
Sounds like that program I wrote 10 years ago for a bank. Only 8,2% of the code is actually used today.
Pexeso
1 / 5 (2) Jul 25, 2014
IMO it's probable, the rest of DNA is serving for similar purpose, like the dark matter for galaxies - it contains an immune apparatus, which prohibits the species in mutual infection and merging via horizontal gene transfer in similar way, like the dark matter prohibits the merging of galaxies. We could therefore call the "junk DNA" the genetic dark matter.
Torbjorn_Larsson_OM
5 / 5 (3) Jul 25, 2014
This is close to the usual estimates, naturally since they are based on the same methodology, but this thorough repeat shows the estimates are correct. The usual estimates topped at 20 %, but of course these are the pessimistic (low) constraints.

And as usual, never mind the anti-science pheromone troll. Funny, I thought the anti-science creationist trolls would be all over this, they like to think that there is genetic "information" in the unused DNA despite that (say) this result is based on that such DNA is changed faster.
Torbjorn_Larsson_OM
5 / 5 (4) Jul 25, 2014
@Scottingham, NRepulsive, Pexeso: The evolutionary function rejects your claims of 'something more'. Extraordinary claims need extraordinary evidence, so you have your work cut out to show that other function is somehow (how?) conserved.

Specifically on "junk DNA", the non-functional DNA isn't it. From the beginning it was pseudogenes (just disused genes that could be potentially reused in whole or parts), but reuse "junk" has been observed to be more.

Same goes for "structural considerations", it doesn't pass the Onion test. Geneticist Gregory Ryan's test on DNA length using polyploidy in, say, onions - despite widely differing DNA content due to chromosome doubling in especially plants, they are related and alike. If the structural consideration is correlated to DNA length, no dice.
Captain Stumpy
5 / 5 (1) Jul 25, 2014
The mouse-to-human model of nutrient-dependent pheromone-controlled ecological variation that leads to a base pair change and single amino acid substitution that differentiates cell types links
let me clarify that more accurately for you...

it LINKS MUTATION and PROVES THAT MUTATION is the basis for ecological variation and supports the Theory of Evolution by showing "a" mutation mechanism.

your model that you keep touting, jk, is PROOF that MUTATIONS are responsible for variation...
but it is also ONLY ONE MECHANISM... not the only mechanism as you say.

as you have already shown... your model creates MUTATIONS: remember.. I asked
DOES your model make any changes to the nucleotide sequence of the genome of an organism, virus, or extrachromosomal genetic element?
This is a yes or no answer
THIS IS THE DEFINITION OF MUTATION - to which you answered
YES!
--Thanks for asking


russell_russell
5 / 5 (1) Jul 25, 2014
Four is the number of DNA bases.

Imagine a structure for which there is no shorter length than the length exhibited to create a human when given only those four bases
.
Now draw an analogy to the lengths of the proofs for mathematics.
Proven in mathematics are only the lower bounds on the lengths of proofs.

The lower bound for the four color theorem is long. Any shorter proof than the proof proven to be needed for the theorem is insufficient - like saying that anything longer in length arising from the incomplete understanding of DNA structure is "junk".

Unrelated further reading:
http://users.math...ngth.pdf

JVK
1 / 5 (3) Jul 25, 2014
I thought the anti-science creationist trolls would be all over this, they like to think that there is genetic "information" in the unused DNA despite...


This is what serious scientists think: Biophysically-constrained nutrient-dependent pheromone-controlled ecological adaptations are epigenetically effected by ecological variation.

"The information that gives rise to form and function is dispersed throughout the organism in the constituent cellular phenotypes and derives mainly from the interactions between information bearing proteins. The concept of a gene, beyond a means of specifying the amino acid sequences of the peptides from which the proteins are formed, is both mostly unnecessary and possibly misleading."

Nutrient-dependent pheromone-controlled alternative splicings of pre-mRNA and amino acid substitutions determine cell type differentiation via conserved molecular mechanisms in species from microbes to man -- as the Creationist Dobzhansky noted in 1964 and 1973.
ViperSRT3g
not rated yet Jul 28, 2014
Not sure if I may have missed it in the article, but I don't think it mentioned any repeated gene coding.

Like Torbjorn was saying, repeated gene coding can also be useful information in itself. Where lack of a repeat in code can cause problems just as much as having repeated coding there in the first place.

The "junk" DNA can still have semi-useful information in it like this repeated code example strewn all throughout the extra parts. It just probably hasn't fit in with the definition of "important" used in this study, or if there is an abundance of it actually present.
antialias_physorg
5 / 5 (2) Jul 28, 2014
The article seems to indicate that repeat sequences and the like were considered (if they are not changed then they are part of their definition).

However I'm not too sure about this part:
with only 8% being functional, we have to work out the 8% of the mutations detected that might be important. From a medical point of view, this is essential to interpreting the role of human genetic variation in disease

While I agree that a change in the functional parts most likely is an indicator of disease I wouln't dismiss any mutations in the rest. It's pretty possible that a hitherto non-functional part can become (detrimentally) functional through mutation.

And as they note: Multiple mutations that have the same effect (parallel evolution) is not captured by this 8% figure.
JVK
1 / 5 (2) Jul 28, 2014
Does anyone else here realize that gene duplication is nutrient-dependent?

I continue to read comments that imply people think that de novo creation of functional genes results from mutations and natural selection in the context of the evolution of biodiversity.

Yet, Torbjorn implies I am a creationist troll, as if my focus on the experience-dependent de novo creation of olfactory receptor genes, makes me the fool.
Captain Stumpy
5 / 5 (2) Jul 28, 2014
Yet, Torbjorn implies I am a creationist troll, as if my focus on the experience-dependent de novo creation of olfactory receptor genes, makes me the fool
@jk
no... your inability to comprehend the lexicon of your chosen "field of study" is what makes you a fool...
your comments like this
I continue to read comments that imply people think that de novo creation of functional genes results from mutations and natural selection in the context of the evolution of biodiversity
makes you a fool

your argument against mutations when your own model CAUSES MUTATIONS makes you the fool

your attempts to hijack any biology thread to sell your pheromone idea makes you the fool

Your constant blatantly ignoring empirical data for your own faith makes you the fool

your continuing insistence that your model is the ONLY means to describe diversity makes you a fool... ESPECIALLY when your model describes DIVERSITY etc BY CAUSING MUTATIONS!

Try accepting empirical data
stop being a FOOL
JVK
1 / 5 (1) Jul 31, 2014
http://www.educat...olution/

"...learning about evolution is not the primary function of the decision, but rather to use it as a building block for students to learn more about their ecology."

Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems
http://figshare.c...s/994281
Arties
not rated yet Jul 31, 2014
The evolutionary function rejects your claims of 'something more'.
When I say, the "junk" DNA helps the speciation, then I don't deny its evolutionary function - on the contrary. This function just doesn't manifest itself with immediate improvement of fitness - but with prohibiting of gradual fitness decay. We should also realize, many organisms (like the Tetraodontidae pufferfishes) essentially lack this junk DNA, which is the key in understanding of its evolutionary function. The human genome is diluted with so much junk DNA that genes are contained in only three percent of it—compared to fifteen percent in the pufferfish. In 2004, researchers reported the creation of mice lacking approximately 3% of their genome in the junk DNA areas - and these mices remained happy. We just didn't confront them with another species outside of lab.