ONLY 8.2% OF HUMAN DNA IS LIKELY TO BE DOING SOMETHING IMPORTANT – IS ‘FUNCTIONAL’ – SAY OXFORD UNIVERSITY RESEARCHERS
From FMS Global News Desk of Jeanne Hambleton Oxford University Date 25 July 2014 PLOS Genetics.
The figure of 8.2% 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.
We tend to have the expectation that all of our DNA must be doing something. In reality, only a small part of it is
Dr Chris Rands
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 do not 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 is not 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 would 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 human genome 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.
Not all DNA is equal
‘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.’
Every mammal has approximately the same amount of functional DNA…Biologically, humans are pretty ordinary in the scheme of things, I am afraid.
Professor Chris Ponting
Of mice and men
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 is not shared between mice and humans, we cannot 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 is 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 am definitely not of the opinion that mice are bad model organisms for animal research. This study really does not address that issue,’ he notes. 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 definitely not of the opinion that mice are bad model organisms for animal research. This study really does not address that issue,’
WHAT CAN OUR DNA REALLY TELL US ABOUT OURSELVES?
From the FMS Global News Desk of Jeanne Hambleton ThingsWeDontKnow.com TWDK by James Duval
Looking in the mirror – what can you see? Blue eyes or brown? Red hair or fair? You do not need to delve into your DNA to find out what physical attributes you have, but how much can the code hidden deep inside your cells tell you about what diseases you are susceptible to, what you will pass onto your children or how long you will live?
Science Fiction or Fact?
At the end of the last century the whole history of genetic research, from Gregor Mendel investigating the principles of inheritance1 to the discovery of the nucleotide structure of DNA2, led inevitably to the Human Genome Project (HGP).
The project’s aims were to look at the sequence of human DNA along with the location of genes and sections associated with inherited disease. As a project it felt monumental, not only within the scientific community, but to society as a whole. It was a project that captured the public imagination, inspiring both hopes and fears for the information it would give us. Would we be designing our own babies? Could we eradicate human disease or alter our genetic codes to enhance intelligence or perhaps sporting prowess?
Essentially, how comfortable are we ‘playing God’ with our own genetic material?
So in the ten years since the full sequence was published3, what has the Human Genome Project and subsequent research into the twists and turns of our DNA actually revealed about us, or rather, about you?
A Study In Susceptibility
The ability to sequence entire genomes of data – 6 billion base pairs – has led to the rise of genome-wide association studies, scanning through millions of markers in a large number of people to find the genetic variations that are associated with a particular disease. So, what have we found so far?
In recent years the susceptibility to a wide-range of complex traits has been studied, from type 2 diabetes to age-related macular degeneration to prostate cancer, but only very small proportions of their genetic risks have been explained.
For example, type 2 diabetes has been deemed a particular success with 36 loci identified that are associated with the disease4. However, although studies have shown that heritability of the disease is greater than 50%4 the variants found so far only account for somewhere between 10. and 30%6. of this. And more than that, most results are only a correlation between areas on a chromosome, rather than the identification of the specific genetic elements that are causing the disease.
So, what does it all really mean to the rest of us?
These common diseases are called complex for a reason. It is not as easy as gene = disease or even 30 genes = disease. Whether you get a disease is a complicated interaction of a large number of genetic factors, each with a small effect7, along with an individual’s environment
Let us take the FTO gene, associated with both obesity and body mass index8, as a particularly pertinent example as obesity-rates continue to rise. The FTO gene has 2 versions, one of which if you carry it in either one copy or two copies will increase your susceptibility to an increased BMI, and in turn obesity. That does not mean that having the risk variant means you will be fatter, but more that your physical chemistry means you are more susceptible to putting on weight – a fact that you probably already knew without having to carry out expensive tests.
So can this, and other disease-related genetic information, be used to provide a basis for treating everyone on an individual basis, taking their genetic and environmental information into consideration. The answer is not quite yet.
Would you really want to know?
With new scientific developments, at some point comes the question of ‘should we?’ Surely most people would opt to know about their propensity for certain diseases if interventions were possible, like changing their behaviour or receiving early medical screenings or treatment. Rather than just presuming we all would, the Sanger Institute is asking the general public questions about what information we should receive from investigations into our genomes.
Currently genetic testing for disease is limited to those rarer diseases that are caused by a single gene, such as cystic fibrosis, which can be used in families with a history of the disease to inform their future decisions about starting a family.
There are maps of the molecular genetic epidemiology of cystic fibrosis
But what about those diseases with a strong genetic component that cannot be prevented yet?
Would you want to know that Alzheimer’s or Parkinson’s was waiting for you, without the ability to treat it? Whatever your thoughts, being able to identify those at risk is an important first step towards developing, or at least testing, a cure. In fact research is already underway to find an early diagnostic test for Alzheimer’s and a survey on public attitudes to such a test9 showed demand could be high.
These are the ethical issues we, and our children, will have to consider as research continues to pick apart our genomes, and tease out the information.
The Fountain of Youth
Perhaps the real question on everyone’s lips is whether our DNA holds the key to an extended life. Researchers have been chasing the internal fountain of youth10 for some time – looking to see whether our genetics can answer questions, such as why we age, when it starts and whether it can be delayed.
While research into aging in mice has revealed some interesting results11, leading to theories that have implications for possible anti-aging interventions in humans-at the moment this is all just theory and would not be producing a miracle cream any time soon.
Most people are interested in what their DNA can tell them about their future, or what they will be passing down the family line to their children, but our DNA also holds the key to our past. It has become so easy to look into our personal, biological codes and find out who our parents, children or siblings are that relationship testing is now incredibly common, and even used as a tool on TV programmes.
Tests that look into your genetic ancestry are now available to trace your maternal or paternal line back even further or look deeper into your ethnicity. This allows us to get a clearer idea of our place in the world, though how accurate the information that can be gleaned from such tests is still in debate.
But, rather than looking at the past, where is the future for the use of our personal genetic information?
Our DNA holds more than just information about the genes that cause rare disease or our risk of complex disease, but can also, perhaps more significantly, reveal how we will respond to treatment for such diseases.
Rather than a ‘one size fits all’ approach to healthcare our genetic information can reveal how we would respond to certain drugs, an area of research known as pharmacogenetics, helping decisions about dosage or warning of adverse effects
For example, information on genetic differences that affect the metabolism of warfarin12, which is prescribed for conditions caused by blood clots, is being used as part of a more accurate personalised dosage regime.
In the future it is thought that this will expand, seeing drug companies developing tests to that will identify those who will respond positively to medication. This will mean that your individual reaction to treatment can be tested before it is even prescribed13, improving the efficiency and success of treatment, personalised just for you.
Ten years after the full sequence of the human genome was published the amount that we hve learnt as a species about our DNA has been massive. How well that data will translate into tangible information about our past and our future is still being debated, but the positive message is that we are in an age of discovery, laying foundations for massive strides forward into disease prediction, personalised medicine and perhaps even science fiction level predictions of our individual futures.
But whatever our DNA can tell us, it is best to look both ways at the traffic lights as no-one can ever really know what life has in store for them.
James Duval is a technology expert, whose interests lie in a wide-range of subjects.
WEBSITE SALES OF ‘DNA TESTS’ TAKEN AT HOME SET
From the FMS Global News Desk of Jeanne Hambleton
On the back of an expected boom in sales of consumer DNA tests this year, a UK company has today launched a new website – dnatestingchoice.com – the worlds first comparison site for ‘DNA testing’ enabling consumers to buy, compare and contrasts.
These DNA tests can be taken at home. It is the world’s first news and review site for the burgeoning home DNA testing market.
The site is the brainchild of biology scholar and online marketing guru Craig Macpherson who has seen first hand how the explosion of DNA tests taken at home have helped thousands to learn more about their genetic disposition.
The new website is championed by TV shows like The Jeremy Kyle Show and CSI where tests are often the centre piece of the programme. DNA testing is set to become big business for UK and a major hobby for British people interested in learning about their roots and genetic predisposition to disease, encouraged by cheaper and more widely available tests.
The in-house editorial team, dnatestingchoice.com has a valuable news element which provides access to the very latest genetic research from around the world – translating it into a language that the general public will understand and allowing them to paint a picture of what the DNA testing products of the future will look like.
Craig Macpherson said, “‘dnatestingchoice.com is designed to make sense of the minefield which is the UK consumer DNA testing market. The Internet is full of companies selling over 900 different tests with no standard pricing structure.
“We aim to show people what is available and what are the best buys with a ‘Tripadvisor’ style model allowing consumers to share their experiences and make informed choices after reading public and expert reviews alongside the very latest information on genetics.”
Craig Macpherson added, “Our DNA is a map of our family history and in particular a key to understanding our risk of predisposition to certain diseases. I share the ‘Secretary of Health’ Jeremy Hunt’s view that Britain should become the first country in the world to routinely sequence people’s genomes to help the NHS plan for our futures. This information is invaluable for helping a new industry of genetic counsellors, which I believe is required, to recommend lifestyle changes and treatments to enable patients to stay healthy for longer”.
The use of ‘DNA Testing’ in health maintenance and disease prevention came to the fore last year after Angelina Jolie learnt she had a 87% genetic predisposition to breast cancer and this allowed the Hollywood actress to make a personal decision to have a full mastectomy.
82% of British Women (21.2m) are aware of Angelina Jolie’s decision to have a mastectomy after taking a DNA test – YouGov Survey December 2013 on behalf of dnatestingchoice.com
Health predisposition tests are expected to be the biggest growth area as people are expected turn to their genome for answers to an array of questions about better and longer health changing the face of healthcare in this country. It is estimated that one in 17 people develop rare diseases in their lifetime, 80 percent of which have a known genetic cause.
The cost of a ‘DNA test’ has plummeted in recent years as advances in technology have been made and demand increased. Costs for an ancestry test start at £62; health genetic disposition at £62 and paternity at anything from £88. The increase in public ancestry testing has been spurred on by TV programmes like ‘ITV’s Long Lost Family, which have encouraged consumers to look into their ancestral roots.
On the growth of the DNA testing market in the UK Craig Macpherson added, “Since the first direct to consumer DNA test was offered nearly a decade ago the public have gradually become more comfortable with buying DNA tests to be taken at home. We are now seeing acceleration in the market where the number of providers has doubled in the last two years. My site is a trusted resource to help steer people through the jungle and realise the benefits of DNA testing”.
- DNAtestingchoice.com enables UK consumers to buy, compare and contrast the latest DNA tests to be taken at home as well as access the most up-to-date information on genetics pooled from worldwide research re-written in layman’s terms.
The site rates 99% of the UK providers and covers the full range of available consumer tests for paternity, health risk and ancestral roots that are among the most popular. The company also does genetic health, maternity, infidelity, twin and pet testing. They offer genetic profiling, prenatal paternity test, family tree DNA not just the UK, plus many more choices.
The website is designed to encourage people to look at how consumer tests can give a valuable insight into their future. Will your children be short or tall or even very tall? Will you suffer an in curable disease that you could possibly avoid with the all important DNA information?
According to Google Trends, searches for the word ‘DNA Test’ have increased by over 100% in the last year.
This year is expected to be the year of the DNA test for 3 reasons: wider availability, reduced price and public awareness of its use in predicting health risk.
Now all I have to do is win the lottery to have several DNA tests done for health, my roots, ancestrally speaking and the future? How long I will live might help. If I win the lottery and can afford all this I will write and tell you what I have found out.
Believe me my ancestry roots are a real teaser. My grandfather was a French Canadian and you would think he was born in that country. But no birth certificate like he never was? Bet the DNA team could not solve this one – my family have been trying for year. It does not help, rumour has it he was born in Sherbrooke, Montreal, but they have not heard of him.
But the DNA story is certainly interesting and I have learned a lot researching this.
In passing we have a new fibromyalgia website as we have been forced out of the original situation by in excess of 8,000 spammers who have jammed up the site and dashboard, meaning we cannot delete them. Our new site is with WordPress is follypogsfibromyalgiaresearch.wordress.com. You have to be thinking when you are typing this one or you end up with someone selling things we do not wish to know about. I suppose we all have to try to earn a living.
While I am advertising do drop in at jeannehambleton77.wordpress.com “just another weblog” as they say here. Just going to do my blog on that site right now. Maybe see you over there.
Take care, talk soon, Jeanne