Two people are dancing a waltz, and it is not going well. One is tall and the other short; one is graceful, the other flat-footed; and both are stepping to completely different rhythms. The result is chaos, and the dance falls apart. Their situation mirrors a problem faced by all complex life on Earth. Whether we’re animal or plant, fungus or alga, we all need two very different partners to dance in step with one another. A mismatch can be disastrous.
Virtually all complex cells – better known as eukaryotes – have at least two separate genomes. The main one sits in the central nucleus. There’s also a smaller one in tiny bean-shaped structures called mitochondria, little batteries that provide the cell with energy. Both sets of genes must work together. Neither functions properly without the other.
Mitochondria came from a free-living bacterium that was engulfed by a larger cell a few billion years ago. The two eventually became one. Their fateful partnership revolutionised life on this planet, giving it a surge of power that allowed it to become complex and big (see here for the full story). But the alliance between mitochondria and their host cells is a delicate one.
Both genomes evolve in very different ways. Mitochondrial genes are only passed down from mother to child, whereas the nuclear genome is a fusion of both mum’s and dad’s genes. This means that mitochondria genes evolve much faster than nuclear ones – around 10 to 30 times faster in animals and up to a hundred thousand times faster in some fungi. These dance partners are naturally drawn to different rhythms.
This is a big and underappreciated problem because the nuclear and mitochondrial genomes cannot afford to clash. In a new paper, Nick Lane, a biochemist at University College London, argues that some of the most fundamental aspects of eukaryotic life are driven by the need to keep these two genomes dancing in time. The pressure to maintain this “mitonuclear match” influences why species stay separate, why we typically have two sexes, how many offspring we produce, and how we age.
No expecting mother would ever wish harm to befall her children. Unfortunately, she may have no choice in the matter. Due to the rules of genetics, mums always run the risk of passing a “mother’s curse” onto their sons, but not their daughters.
The curse is an ancient one, the result of events that happened billions of years ago. At a time when all life consisted of single microscopic cells, one of these swallowed another. Normally, the engulfed cell would be digested, but not this time – this time, the two cells formed an alliance. The swallowed cell transferred many of its genes to its host, keeping only those involved in providing energy. It evolved into a mitochondrion – a tiny, efficient battery that would power its host, giving it the energy to become more complex. This alliance is the foundation of all complex life on the planet. All animals, plants, fungi and algae run on mitochondria power.
This means that all animals really have two genomes – their main nuclear one, and a far smaller secondary one in their mitochondria. The two sets of genes work together, each controlling the activity of the other. But they are inherited differently. The nuclear genome is a mash-up of genes from both parents, but the mitochondrial one only comes from mum. And this asymmetry is the reason for the mother’s curse.
The 21st century is all about conserving energy. The push towards energy-efficient buildings, vehicles and lifestyles is both fashionable and necessary, but it’s also ironic. Our pattern of ever-increasing energy consumption is deeply rooted in our history, not just since the Industrial Revolution, but since the origin of all complex life on Earth.
According to a new hypothesis, put forward by Nick Lane and Bill Martin, we are all natural-born gas-guzzlers. Our very existence, and that of every animal, plant and fungus, depended on an ancient partnership, forged a few billion years ago, which gave our ancestors access to unparalleled supplies of energy and allowed them to escape from the shackles of simplicity.
The Not Exactly Pocket Science experiment continues after the vast majority of people who commented liked the pilot post. I’m really enjoying this, for quite unexpected reasons. It’s forcing me to flex writing muscles that usually don’t get much of a workout. Writing short pieces means being far more economical with language and detail than usual. It means packing in as much information as possible while still keeping things readable. And it means blitz-reading papers and writing quickly without losing any accuracy.
One quick note before the good stuff: last time, a few people suggested that I put each NEPS item in a separate post, but the majority preferred multiple items per post. For now, I’m keeping it that way because otherwise, the longer pieces would be diluted by the smaller ones. We’ll see how that works for the foreseeable future.
Rising DAMPs – when enslaved bacteria turn our bodies against themselves
Our immune systems provide excellent defence against marauding hordes of bacteria, viruses and parasites, using sentinel proteins to detect the telltale molecules of intruders. But these defences can be our downfall if they recognise our own bodies as enemies.
All of our cells contain small energy-supplying structures called mitochondria. They’re descendents of ancient bacteria that were engulfed and domesticated by our ancestor cells. They’ve come a long way but they still retain enough of a bacterial flavour to confuse our immune system, should they break free of their cellular homes. An injury, for example, can set them free. If cells shatter, fragments of mitochondria are released into the bloodstream including their own DNA and amino acids that are typical of bacteria. Qin Zhang showed that trauma patients have far higher levels of such molecules in their blood than unharmed people. Our white blood cells have sentinel proteins that latch onto these molecules and their presence (incorrectly) says that a bacterial invasion is underway.
This discovery solves a medical mystery. People who suffer from severe injuries sometimes undergo a dramatic and potentially fatal reaction called “systemic inflammatory response syndrome” or SIRS, where inflammation courses through the whole body and organs start shutting down. This looks a lot like sepsis, an equally dramatic response to an infection. However, crushing injuries and burns can cause SIRS without any accompanying infections. Now we know why – SIRS is caused by the freed fragments of former bacteria setting off a false alarm in the body. The technical term for these enemies within is “damage-associated molecular patterns” or DAMPs.
More from Heidi Ledford at Nature News
Reference: Nature DOI:10.1038/nature08780
Different gut bacteria lead to mice to overeat
On Wednesday, I wrote about the hidden legions residing up your bum – bacteria and other microbes, living in their millions and outnumbering your cells by ten to one. These communities wield a big influence over our health, depending on who their members are. Matam Vijay-Kumar found that different species colonise the guts of mice with weakened immune systems, and this shifted membership is linked to metabolic syndrome, a group of obesity-related symptoms that increase the risk of heart disease and type 2 diabetes.
Vijay-Kumar’s mice lacked the vital immune gene TLR5, which defends the gut against infections. Their bowels had 116 species of bacteria that were either far more or less common than usual. They also overate, became fat, developed high blood pressure and became resistant to insulin – classic signs of metabolic syndrome. When Vijay-Kumar transplanted the gut menagerie from the mutant mice to normal ones, whose own bacteria had been massacred with antibiotics, the recipients also developed signs of metabolic syndrome. It was clear evidence that the bacteria were causing the symptoms and not the other way round.
Vijay-Kumar thinks that without the influence of TLR5, the mice don’t know what to make of their unusual gut residents. They react by releasing chemicals that trigger a mild but persistent inflammation. These same signals encourage the mice to eat more, and they make local cells resistant to the effects of insulin. Other aspects of the metabolic syndrome soon follow. The details still need to be confirmed but for now, studies like this show us how foolish it is to regard obesity as a simple matter of failing willpower. It might all come down to overeating and inactivity, but there are many subtle reasons why an individual might eat too much. The microscopic community within our guts are one of them.
Reference: Science DOI:10.1126/science.1179721
The stretchy iron-clad beards of mussels
For humans, beards are for catching food, looking like a druid, and getting tenure. But other animals have beards with far more practical purposes – mussels literally have beards of iron that they use as anchors. The beard, or byssus, is a collection of 50-100 sticky threads. Each is no thicker than a human hair but they’re so good at fastening the mussels to wave-swept rocks that scientists are using them as the inspiration for glue. So they should. The byssus is a marvel of bioengineering – hard enough to hold the mussel in place, but also stretchy enough so that they can extend without breaking.
The mussel secretes each thread with its foot, first laying down a protein-based core and then covering it in a thick protective layer that’s much harder. When Matthew Harrington looked at the strands under a microscope, he saw that the outer layer is a composite structure of tiny granules amid a looser matrix. The granules consist of iron and a protein called mfp-1, heavily linked to one other – this makes the byssus hard. The matrix is a looser collection of the same material, where mfp-is 1 heavily coiled but easy to straighten – this lets the byssus stretch. The granules have a bit of give to them but at higher strains, they hold firm while the matrix continues extending. If cracks start to form, the granules stop them from spreading.
It’s unclear how the mussel creates such a complicated pattern, but Harrington suggests that it could be deceptively simple – changing a single amino acid in the mfp-1 protein allows it to cross-link more heavily with iron. That’s the difference between the tighter granular bundles, and the looser ones they sit among.
Reference: Science DOI:10.1126/science.1181044
Cause of dinosaur extinction
Sixty-five million years ago, the vast majority of dinosaurs were wiped out. Now, a new paper reveals the true cause of their demise – legions of zombies armed with chaingu… wait… oh. Right. An asteroid. You knew that.
More from Mark Henderson at the Times
Reference: Science DOI:10.1126/science.1177265
At first glance, the African elephant doesn’t look like it has much in common with us humans. We support around 70-80 kg of weight on two legs, while it carries around four to six tonnes on four. We grasp objects with opposable thumbs, while it uses its trunk. We need axes and chainsaws to knock down a tree, but it can just use its head. Yet among these differences, there is common ground. We’re both long-lived animals with rich social lives. And we have very, very large brains (well, mostly).
But all that intelligence doesn’t come cheaply. Large brains are gas-guzzling organs and they need a lot of energy. Faced with similarly pressing fuel demands, humans and elephants have developed similar adaptations in a set of genes used in our mitochondria – small power plants that supply energy to our cells. The genes in question are “aerobic energy metabolism (AEM)” genes – they govern how the mitochondria metabolise nutrients in food, in the presence of oxygen.
We already knew that the evolution of AEM genes has accelerated greatly since our ancestors split away from those of other monkeys and apes. While other mutations were reshaping our brain and nervous system, these altered AEM genes helped to provide our growing cortex with much-needed energy.
Now, Morris Goodman from Wayne State University has found evidence that the same thing happened in the evolution of modern elephants. It’s a good thing too – our brain accounts for a fifth of our total demand for oxygen but the elephant’s brain is even more demanding. It’s the largest of any land mammal, it’s four times the size of our own and it requires four times as much oxygen.
Goodman was only recently furnished with the tools that made his discovery possible – the full genome sequences of a number of oddball mammals, including the lesser hedgehog tenrec (Echinops telfairi). As its name suggests, the tenrec looks like a hedgehog, but it’s actually more closely related to elephants. Both species belong to a major group of mammals called the afrotherians, which also include aardvarks and manatees.
Goodman compared the genomes of 15 species including humans, elephants, tenrecs and eight other mammals and looked for genetic signatures of adaptive evolution. The genetic code is such as that a gene can accumulate many changes that don’t actually affect the structure of the protein it encodes. These are called “synonymous mutations” and they are effectively silent. Some genetic changes do, however, alter protein structure and these “non-synonymous mutations” are more significant and more dramatic, for even small tweaks to a protein’s shape can greatly alter its effectiveness. A high ratio of non-synonymous mutations compared to synonymous ones is a telltale sign that a gene has been the target of natural selection.
And sure enough, elephants have more than twice as many genes with high ratios of non-synonymous mutations to synonymous ones than tenrecs do, particularly among the AEM genes used in the mitochondria. In the same way, humans have more of such genes compared to mice (which are as closely related to us, as tenrecs are to elephants).
These changes have taken place against a background of less mutation, not more. Our lineage, and that of elephants, has seen slower rates of evolution among protein-coding genes, probably due to the fact that the duration of our lives and generations have increased. Goodman speculates that with lower mutation rates, we’d be less prone to developing costly faults in our DNA every time it was copied anew.
Overall, his conclusion was clear – in the animals with larger brains, a suite of AEM genes had gone through an accelerated burst of evolution compared to our mini-brained cousins. Six of our AEM genes that appear to have been strongly shaped by natural selection even have elephant counterparts that have gone through the same process.
Of course, humans and elephants are much larger than mice and tenrecs. But our genetic legacy isn’t just a reflection of our bigger size, for Goodman confirmed that AEM genes hadn’t gone through a similar evolutionary spurt in animals like cows and dogs.
Goodman’s next challenge is to see what difference the substituted amino acids would have made to us and elephants and whether they make our brains more efficient at producing aerobic energy. He also wants to better understand the specific genes that have been shaped the convergent evolution of human and elephant brains over the course of evolution. That task should certainly become easier as more and more mammal genomes are published.
Reference: PNAS doi:10.1073/pnas.0911239106
More on elephants: