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Earlier this year, UK Parliament voted to change the law to support new and controversial in-vitro fertilisation (IVF) procedures known as ‘mitochondrial donation’. The result is that the UK is at the cutting-edge of mitochondrial science and the only country in the world to legalise germ-line technologies. The regulations came into force on 29th October this year, and clinics are now able to apply for a licence.

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On 25th March 2015, 530 years after his death, King Richard III of England will be interred in Leicester Cathedral. This remarkable ceremony is only taking place because of the success of DNA analysis in identifying his skeletal remains. So what sort of genes might a king be expected to have? Or, more prosaically, how do you identify a long dead corpse from its DNA? Several methods were used, and in particular the deduction of the skeleton’s probable hair and eye colour raises some interesting questions about future trends in forensic DNA analysis.

Richard III is one of England’s best known kings, largely due to the famous play of William Shakespeare in which he is portrayed as an evil villain. He only reigned for two years and was killed at the age of 32 at the battle of Bosworth in 1485. According to the historical records he was unceremoniously buried at Greyfriars Friary in Leicester. At some stage knowledge of the exact location of Richard’s burial was lost. But in 2012 excavations under a car park at the probable site of the former friary yielded “skeleton 1″. Suspicion of his royal identity was excited by the fact that the skeleton had a severely bent spine causing the right shoulder to be higher than the left. This well-known deformity of Richard was mentioned in a contemporary source, as well as by Shakespeare. Furthermore, the skeleton was male, the age was about right, it had evidently been killed in battle, and the radiocarbon date was consistent with death in 1485.

This was all very suggestive, but it was the DNA analysis that really proved the case. The work was led by a team at the University of Leicester, with participation by many other UK and European centres. It is important to note that this was not the normal type of forensic DNA identification, which relies on comparing a set of highly variable DNA markers to a database. Such analysis is fine so long as your suspect is in the database, but it is no use for identifying a long dead individual who is not in any database.

By far the best evidence for the identity of Richard III comes from the analysis of his mitochondrial DNA. Mitochondria are bodies found in every cell, responsible for the production of energy. They have their own DNA which is passed down the generations only through the female line. Barring the occasional new mutation, the DNA sequence of mitochondrial DNA should be identical from mother to daughter down a particular female line of descent. Like their sisters, males also carry the mitochondrial DNA of their mothers, but they do not pass it down to their own offspring.

Richard will have shared mitochondrial DNA with his sister, Anne of York. Two complete female lines of descent were traced back to Anne of York, one of 17 generations down to Michael Ibsen, a resident of London, and the other of 19 generations down to Wendy Duldig, formerly of New Zealand. Complete sequencing of their mitochondrial DNA showed a 100% match between skeleton 1 and of Michael Ibsen, and a single base change compared to Wendy Duldig. One change over this period of time is quite likely to be a new mutation. The sequence family (haplogroup) to which the mitochondrial DNA sequence belongs is a fairly rare one, so few other people in England in 1485 would have shared it and in fact the team has systematically ruled out all the other males of the period who might have shared it because of a common female lineage with Richard III. So this match is highly significant and is the best piece of evidence that the “skeleton 1″ is indeed King Richard.

Also applied was a newer method which is a technique for predicting the hair and eye colour of someone from their DNA. The most important variants affecting hair colour are mutations of a gene called MC1R, which encodes a cell surface receptor for a hormone. Individuals carrying variants of the MC1R gene with reduced function are likely to have red or blond hair rather than the normal dark hair. The pigmentation of the iris of the eye depends significantly on a gene called OCA2, encoding a protein which transports tyrosine into cells. Again variants of reduced function give less pigmented eyes, meaning that the colour is blueish rather than brownish. Recently a Dutch group created a forensic test based on variants at 24 genetic loci, of which 11 are in the MC2R gene and the rest in 12 other positions including the OCA2 gene. Identification of these 24 variants yields a fairly accurate prediction of hair and eye colour, and in the case of skeleton 1 the prediction was for blue eyes and blond hair. The existing portraits of Richard III all date from some time after his death but the older ones do indeed show light-coloured eyes and reddish-brown hair, an appearance which is consistent with the prediction.

These two types of analysis indicate two rather different senses in which we use the word “gene”. The sequence variants of the mitochondrial DNA, like those used in normal forensic identification, do not, in general, affect the characteristics of the individuals carrying them. The DNA changes often lie outside actual genes, in the regions of DNA between genes. They are better described as “markers” than as “genes”. But the hair and eye colour analysis is based at least partly on actual gene variants that might be expected to generate those visible characteristics.

How much further might this kind of analysis be pushed? Could the height, facial features or skin colour of a crime suspect be deduced from their DNA? The essential issue is the number of gene variants in the population that affect a feature. If it is relatively small, as with hair and eye colour, then prediction is possible. If it is very large, as for height, then it is not possible, because most of the variants affecting height have too small effects to be detectable. Most of the human characteristics that have been studied in this way have turned out to depend on a very large number of variants of small effect. So, contrary to popular perception, there are real limits to what is possible in terms of prediction of bodily features from DNA data. There will doubtless be some other features that are predictable, and these may eventually include skin colour. But unless a completely new approach is invented, it is unlikely that we shall ever see an identikit picture of a suspect generated from DNA at the crime scene.

Featured image credit: Stained glass, by VeteranMP. CC-BY-SA 3.0 via Wikimedia Commons

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By John Archibald

We humans have a love-hate relationship with bugs. I’m not talking about insects — although many of us cringe at the thought of them too — but rather the bugs we can’t see, the ones that make us sick.

Sure, microorganisms give us beer, wine, cheese, and yoghurt; hardly a day goes by without most people consuming food or drink produced by microbial fermentation. And we put microbes to good use in the laboratory, as vehicles for the production of insulin and other life-saving drugs, for example.

But microbes are also responsible for much of what ails us, from annoying stomach ‘bugs’ to deadly infectious diseases such as tuberculosis and plague. Bacteria and viruses are even linked to certain cancers. Bugs are bad; antibiotics and antivirals are good. We spend billions annually trying to rid ourselves of microorganisms, and if they were to all disappear, well, all the better, right?

This is, of course, nonsense. Even the most ardent germaphobe would take a deep breath and accept the fact that we could no more survive without microbes than we could without oxygen. No matter how clean we strive to be, there are 100 trillion bacterial cells living on and within our bodies, 10 times the number of human cells that comprise ‘us’. Hundreds of different bacterial species live within our intestines, hundreds more thrive in our mouths and on our skin. Add in the resident viruses, fungi, and small animals such as worms and mites, and the human body becomes a full-blown ecosystem, a microcosm of the world around us. And like any ecosystem, if thrown off-balance bad things can happen. For example, many of our ‘good’ bacteria help us metabolize food and fight off illness. But after a prolonged course of antibiotics such bacteria can be knocked flat, and normally benign species such as ‘Clostridium difficile’ can grow out of control and cause disease.

Given the complexity of our body jungle, some researchers go as far as to propose that there is no such thing as a ‘human being’. Each of us should instead be thought of as a human-microbe symbiosis, a complex biological relationship in which neither partner can survive without the other. As disturbing a notion as this may be, one thing is indisputable: we depend on our microbiome and it depends on us.

And there is an even more fundamental way in which the survival of Homo sapiens is intimately tied to the hidden microbial majority of life. Each and every one of our 10 trillion cells betrays its microbial ancestry in harboring mitochondria, tiny subcellular factories that use oxygen to convert our food into ATP, the energy currency of all living cells. Our mitochondria are, in essence, domesticated bacteria — oxygen-consuming bacteria that took up residence inside another bacterium more than a billion years ago and never left. We know this because mitochondria possess tiny remnants of bacterium-like DNA inside them, distinct from the DNA housed in the cell nucleus. Modern genetic investigations have revealed that mitochondria are a throwback to a time before complex animals, plants, or fungi had arisen, a time when life was exclusively microbial.

As we ponder the bacterial nature of our mitochondria, it is also instructive to consider where the oxygen they so depend on actually comes from. The answer is photosynthesis. Within the cells of plants and algae are the all-important chloroplasts, green-tinged, DNA-containing factories that absorb sunlight, fix carbon dioxide, and pump oxygen into the atmosphere by the truckload. Most of the oxygen we breathe comes from the photosynthetic activities of these plants and algae—and like mitochondria, chloroplasts are derived from bacteria by symbiosis. The genetic signature written within chloroplast DNA links them to the myriad of free-living cyanobacteria drifting in the world’s oceans. Photosynthesis and respiration are the biochemical yin and yang of life on Earth. The energy that flows through chloroplasts and mitochondria connects life in the furthest corners of the biosphere.

For all our biological sophistication and intelligence, one could argue that we humans are little more than the sum of the individual cells from which we are built. And as is the case for all other complex multicellular organisms, our existence is inexorably linked to the sea of microbes that share our physical space. It is a reality we come by honestly. As we struggle to tame and exploit the microbial world, we would do well to remember that symbiosis—the living together of distinct organisms—explains both what we are and how we got here.

John Archibald is Professor of Biochemistry and Molecular Biology at Dalhousie University and a Senior Fellow of the Canadian Institute for Advanced Research, Program in Integrated Microbial Biodiversity. He is an Associate Editor for Genome Biology & Evolution and an Editorial Board Member of various scientific journals, including Current Biology, Eukaryotic Cell, and BMC Biology. He is the author of One Plus One Equals One: Symbiosis and the Evolution of Complex Life.

Image credit: Virus Microbiology. Public domain via Pixabay

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Every month OUP editor and author Jonathan Crowe answers your science questions in the monthly SciWhys column. Got a burning question about science that you’d like answered? Just email it to us, and Jonathan will answer what he can. Today: Why do we eat food?

By Jonathan Crowe

You may well be thinking that the question posed in the title of this blog has an all-too-obvious answer. We all know that we eat food to keep ourselves alive. But why do we find ourselves slaves to our appetites and rumbling stomachs? What is actually happening inside each of us that couldn’t happen without another slice of toast, or piece of fruit, or that most vaunted of mid-afternoon pick-me-ups, the sneakily-consumed bar of chocolate?

We’re all familiar with the concept of something needing fuel to keep it going. Just as a power station requires gas or coal to power its turbines and generate energy, so we need fuel – in the form of food – to power our continued existence.

The foods we eat provide us with a range of nutrients: vitamins, minerals, water, fat, carbohydrates, fibre, and protein. These nutrients are put to different uses — as building materials to construct the tissues and organs from which our bodies are made; as the components of the molecular machinery that keeps our cells running as they should. All of these uses are unified by a common theme: a requirement for energy to make them happen. And this is where one particular type of nutrient comes into its own. Step forward the carbohydrates.

Carbohydrates are better known to us as sugars, but in fact the sweet crystals we know as sugar are only part of this group. Carbohydrates come in very different shapes and sizes. One of the smallest is glucose, which acts as a chemical building block — multiple copies of glucose can join together to form a range of much larger molecules. For example, starch – found in potatoes and flour – is a carbohydrate formed from many individual molecules of glucose joined together in long chains. (Based on taste alone, you wouldn’t think that starch was made of glucose. Even though individual molecules of glucose taste sweet to us, once they are linked together to form starch the sweetness is lost.)

To understand how the sugar in our food can power the processes occurring in our cells every minute of every day, let’s follow some starch on its journey through the body. Many of the foods we consume aren’t in a form with which our bodies can do anything useful. Instead, they need to be digested. And so it is with carbohydrates such as starch. This process of digestion starts as soon as the food enters our mouth; our saliva contains special substances (called enzymes) that start attacking the long chains of starch, breaking it into smaller fragments.

Digestion continues as our food is swallowed and slides down into our stomach, where an arsenal of other chemical weapons set to work on the mouthful we’ve just consumed. Before long, what were initially mouth-watering morsels are reduced to something rather less appetising and leave the stomach to enter the long, snaking tunnel of our intestines. By now, the long chains of starch have been broken down into glucose, which is small enough to pass through the lining of our intestine and into our bloodstream. Our bloodstream acts as a short- and long-distance transport network, carrying the newly-arrived sugar molecules to cells all over the body.

When glucose arrives at its destination and first enters the cell, it u