Hidden evolution: How the mammoth kept its cool

Last weekend I went to see an exhibition on mammoths in the Natural History Museum in London (unfortunately now closed). The descriptions and posters did a very good job of explaining our current knowledge of mammoths and how that knowledge had been gained. In particular, the curators were very keen to highlight the evolutionary relationships between different mammoth species and modern elephants.

A lot of the differences between the woolly mammoths and modern elephants are quickly apparent. The woolly mammoths are larger, hairier, and of course there are the tusks.

The tusks can be a big giveaway for a mammoth

The tusks can be a big giveaway for a mammoth

But one little sign caught my eye. It said that from the genetic material gathered from mammoth remains (we’ve recorded about 70% of their genome, so maybe not too far off until we can clone mammoths back into existence!), we can tell that woolly mammoths had a mutated form of haemoglobin that worked better in cold temperatures.

This haemoglobin discovery was published in 2010, so it isn’t anything new. But for me, this is evolution at its most interesting – not apes walking upright or fish breathing on land, but the tiny internal changes that adapt the body’s complex machinery.

Haemoglobin has a difficult balancing act to achieve – it needs to grab hold of oxygen from the lungs and it needs to release it around the body. If it holds the oxygen too tightly, the muscles can’t receive enough. If the haemoglobin holds on too weakly, it won’t be able to carry enough oxygen to where it is needed.

Elephant haemoglobin, like the human form, more readily releases oxygen at higher temperatures. That comes down to the energetics of breaking its hold, but it also means that harder-working (and therefore warm) muscles can take a greater share. This can be a serious issue if body-parts get too cold – they can suffocate to death. This is a danger for trekking around Siberia, even if you are large and hairy.

Researchers from the University of Manitoba, Canada, compared the haemoglobin genes of woolly mammoths to those of an Asian elephant from a nearby zoo. They noticed that there were four mutations that led to changes in the amino acid chains of the haemoglobin proteins.

Without any mammoth blood to hand, it can be very difficult to work out the effect of these changes. Fortunately, although we can’t resurrect a full mammoth now, we can insert the haemoglobin DNA into bacteria and resurrect one small part of them.

With the bacterium-produced mammoth haemoglobin, the researchers could run the tests needed to confirm that it was indeed adapted to the cold. Rather than the strong link to temperature seen in elephants, the mammoths’ haemoglobin can release oxygen at a similar level over a wide range of temperatures.

The structure of haemoglobin, with the blue regions showing where the mammoth mutations are

The structure of haemoglobin, with the blue regions showing where the mammoth mutations are (Credit: K Campbell et al, 2010)

The blue regions in the picture above show where the changes are in the structure of haemoglobin. These changes don’t appear to make any direct contact with the heme group (the part that carries the oxygen, shown in orange sticks), but they alter the shape of the protein subtly. This change in shape is enough to give mammoths a better chance of surviving freezing cold environments.

Mutations in haemoglobin are also seen in other animals adapted to cold environments, such as the arctic fox. The mutations seen in these animals are all different but lead to similar effects – an example of convergent evolution.

Just last year, the same researchers who made this discovery started work on an exciting new find: well-preserved mammoth blood. This could give them the chance to test the same idea on haemoglobin straight from a mammoth. There is even a (very small) chance that intact cells could be found in the sample, which would make cloning a full mammoth a lot easier.

So before long we might find out a lot more about these legendary creatures.

Keeping up with the Red Queen: Co-evolution of hosts and pathogens

While most micro-organisms are harmless to humans, and in some cases even beneficial, there are those that are not welcome. These are known as pathogens, from the Greek for ‘producer of suffering’. For us, pathogens can be very damaging and even deadly, and so we have evolved ways to resist their attacks. For the pathogen, infecting a human might be the only chance to survive and reproduce. The potential reward is so great that pathogens will develop ways around our defences. This becomes an ongoing battle and means that neither side can stop evolving in case the opponent becomes too dominant; in the words of the Red Queen from Lewis Carroll’s Through the Looking-Glass: “It takes all the running you can do, to keep in the same place.” This interplay between host and pathogen is known as co-evolution and can lead to very different strategies being used on both sides.

The Red Queen (not to be confused with the Queen of Hearts) and Alice

All-out war

Aggressive strategies, like that used by the malarial parasite Plasmodium falciparum, can drive co-evolution rapidly. Once it has infected a person, the pathogen replicates as quickly as possible. This is risky because it seriously affects the infected human and can even cause death, and if the host dies, the pathogen die with it. This strategy works because P. falciparum spreads between humans via mosquitoes. High concentration of the parasite in the bloodstream is the best way to ensure that they are taken up by a mosquito and passed on to a new host. However, the severity of malaria and the high likelihood of death means there is a strong evolutionary pressure for humans to develop resistance, even if that comes at a price.

Indeed resistance has developed, via a specific mutation in the gene coding for the blood protein haemoglobin. Everyone has two copies of the haemoglobin gene – one from each parent. A mutation in both copies of the gene provides malarial resistance but causes sickle cell anaemia. This causes blood flow to be restricted and eventually leads to premature death, which obviously outweigh any benefits. Fortunately, having just one copy of the mutation maintains some resistance and avoids sickle cell anaemia. However it can never be guaranteed that a child will inherit exactly one copy of the mutated gene, so there is always a risk of children being born with sickle cell anaemia. This means that the level of the mutation present in the population is determined by the balance between the risk of malaria and the risk of sickle cell anaemia. There is little risk of malaria in the UK and so the mutation is rare. In sub-Saharan Africa, where malaria causes a quarter of all deaths in children under five, the balance shifts. The mutated gene is present in up to 40% of the population, meaning that approximately 2% of children are born with sickle cell anaemia.

When a specific glutamic acid residue (highlighted in magenta on the far right) is mutated to a valine it causes haemoglobin molecules to aggregate, which distorts the shape of red blood cells

Under the radar

Evolving against every new infectious disease that we encounter is not possible. Humans, with our relatively slow reproductive rate, take a long time to develop new, beneficial mutations. This is why many infections, such as the common cold caused by the rhinovirus, have evolved to avoid affecting humans severely. Catching a cold will not affect the ability to reproduce, which is the main driving force behind evolution. Without this evolutionary pressure, humans do not appear to have developed mutations to specifically deal with the rhinovirus. Keeping the host able and mobile also has the benefit of boosting the spread of the disease. If the host feels well enough to leave bed and go to work, then the rhinovirus is presented with a wide range of potential hosts with every sneeze.

The immune system provides a flexible defence against a huge variety of diseases, lessening the need to evolve in response to new infections. The system learns to recognise a part of the pathogen known as the antigen, which allows the pathogen to be targeted. This means that a strain of rhinovirus, or any pathogen, that has mutated its antigen can evade detection by the immune system for longer. Unfortunately for us, this happens very often as the rhinovirus mutates very easily and reproduces incredibly quickly, allowing a huge number of mutations to accumulate within a population rapidly.

Gaining ground

Today the risk of dying from an infectious disease is lower than at any point in human history. After thousands of years locked in an impasse with diseases, we have finally developed an advantage through modern medicine. Although it seemed that we have surpassed the power of evolution, pathogens are still working towards breaking through our defences. Whether it is a new strain of flu or an antibiotic-resistant superbug, if we want to maintain our advantage it will take all the running we can do.

Note: this post was updated 16:53 GMT 21/10/2012 to remove any suggestions that Plasmodium falciparum is a bacterium

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Above Genetics: How your behaviour can affect your DNA

It is now regarded as a simple fact of life that you are stuck with the genes your parents gave you. Genetic mutations from long ago have passed down from generation to generation, whether it is joined earlobes, knobbly knees or a higher risk of breast cancer. This is Darwinian inheritance in action.

But what if that isn’t the full story? What if your actions as a ten-year-old not only affected your genes, but those of your future children and grandchildren?

Darwin wasn’t the first to offer a theory on evolution; before him was Jean-Baptiste Lamarck, who suggested that traits developed by animals during their lifetime could be passed onto their children. The classic example is a giraffe, who, after years of stretching to reach higher leaves, would have offspring with longer necks. After several generations of stretching, giraffes would have necks as long as they are today.

This made intuitive sense and even Darwin was reluctant to dismiss it — he was not quite the Darwinist he is now made out to be. However, now that DNA is known to be responsible for passing on genetic information, it is hard to see how this could work. No amount of neck-straining will change your genes, so surely this cannot happen.

How could stretching your neck be passed on to the next generation?
Source: Brocken Inaglory

The Human Genome Project aimed to transcribe our DNA and find out what makes a human. Even after decoding all three billion ‘letters’, there was still not enough information to provide all the answers. One of the problems is that many genes can be switched off, or ‘silenced’, by the body. This occurs through methylation, where a small marker, just one carbon and three hydrogen atoms, is attached to a section of DNA and switches it off. Since this silences a gene without actually altering the genetic code, methylation is described as epigenetic, from the Greek ‘epi-’ for ‘above’. This system of silencing genes is another layer of information on top of the genetic code — an epigenetic code.

Methylation of DNA is a natural way that an organism regulates itself, but external factors can affect this dramatically. When a honey bee larva is fed on royal jelly its methylation levels fall, causing it to develop ovaries, grow larger and live longer, i.e. become a queen. However, it is not just food that is important; mice change their DNA methylation patterns depending on how much attention their mothers paid them as a pup.

Methylation of DNA is a very subtle change but its effects can be enormous.
Source: Christoph Bock

Epigenetic changes due to environment can happen even before birth. Studies of several famines, including the Dutch Hunger Winter of 1944 and the Great Chinese Famine of 1958–61, have shown that children conceived during these periods were underweight at birth. Now adults, they have increased rates of obesity, heart disease and schizophrenia, and have increased methylation of genes linked to these diseases. This makes clear the importance of epigenetics as not just an aside to genetics but a powerful force in its own right.

It was long thought that epigenetic changes could not be passed to our children, as sperm and egg cells undergo ‘reprogramming’ to wipe the slate clean. However, recent experiments have shown that mice are able to pass on epigenetic changes and historical records suggest that this may be happening in humans too.

As an isolated farming community in the early 1800s, Överkalix in north Sweden suffered from extreme fluctuation in food supply; some years would be plentiful while others would be ruinous. This variation encouraged Lars Olev Bygren, a preventative health specialist, to trace the ancestries of a hundred villagers and cross-reference them with harvest records. Remarkably, he found that boys who had survived a year of famine while aged 9–12 went on to have sons and grandsons who lived on average 32 years longer than those of boys who had enjoyed a year of feasting. This prepubescent stage is when the body is most susceptible to environmental changes; however it is remarkable that the repercussions can be seen two hundred years later in the lives of their grandchildren, who were never directly exposed to famine.

This seems very similar to Lamarck’s theory that the impact of an animal’s life is passed down to the next generation. However, epigenetics cannot replace Darwinian inheritance, where a genetic mutation is permanent, as epigenetic changes should only be temporary. But how long is temporary? We have seen effects passed down at least two generations in humans, while experiments with roundworms have shown epigenetic changes surviving over 40 generations.

Epigenetics gives us the flexibility that genetics could never provide, allowing us to adapt to our environment during our lifetime. However, it is not just our own lives being adjusted; we could be determining the lives of our future children. Take heed, the sins of the father may well be visited upon the son.