The natural world is full of great partnerships. Bacteria give animals the guts to digest all manner of otherwise inedible foods. Algae allow corals to harness the power of the sun and construct mighty reefs. Ants cooperate to become mighty superorganisms. But the greatest partnership of all is far more ancient. It’s so old that we can only infer that it took place by looking for signals of history, embedded into the genomes of modern species. The details of how and when it happened are still the source of fierce debate but this was undoubtedly the most important merger in the history of life on Earth: a partnership between two simple cells that would underlie the rise of every living animal, plant, fungus and alga.
Aphids, those sap-sucking foes of gardeners, come in a variety of colours. We usually think of them as green, but pea aphids sometimes wear a fetching red ensemble. That may not strike you as anything special; after all, lots of animals are red. But the aphid’s colour is unique in a couple of extraordinary ways.
The colour comes from pigments called carotenoids. Animals use them for all sorts of purposes; they act as antioxidants, and they contribute to red, orange and yellow colours. But the pea aphid is one of only a few known species (all aphids) that manufacture their own carotenoids; everyone else gets theirs from their food. But it’s the source of the pea aphid’s ability that’s truly remarkable – it stole the skill from fungi. By integrating fungal genes into its own genomes, it gained a superpower that almost all other animals lack.
These sorts of “horizontal gene transfers” go on all the time in bacteria, but they’re supposedly a rarity among more complex creatures like animals and plants. And yet, scientists have recently documented several examples of such transfers. Rotifers smuggle genes from fungi, bacteria and plants. “Space Invader” genes have jumped across animals as diverse as lizards and bushbabies. One bacterium, Wolbachia, has even inserted its entire genome into that of a fruit fly. And parasites can transfer their genes to humans.
In most of these cases, it’s unclear whether the imported genes are actually doing anything useful. But the story of the pea aphid, told by Nancy Moran and Tyler Jarvik, is very different. The colour of a pea aphid determines the predators that target it. Ladybirds (one of their major enemies) prefer to attack red aphids on green plants but parasitic wasps are more likely to lay their eggs in green aphids, to fatal effect. Colour clearly matters to an aphid, so here is a clear example of a transferred gene shaping an obvious trait in its new host and in doing so, shaping its evolution.
During our early childhoods, the vast majority of us are boarded by a stowaway that can stay with us for the rest of our lives. It can rear its head when we are at our weakest and it can wriggle its way down our family tree into our children and grandchildren. It’s a virus called human herpesvirus-6, or HHV-6 for short. It’s probably in your genome right now.
As its name suggests, HHV-6 is one of the herpesviruses. Unlike other members, it doesn’t actually cause herpes, but it is one of the most common infections in the Western world. It infiltrates the bodies of over 90% of children and it causes a near-universal disease called ‘exanthema subitum’, also known as roseola or three-day fever. The signs of infection soon clear out, but the virus stays put.
Like all herpesviruses, HHV-6 can enter a dormant phase called “latency”, where it stays in our cells after the initial infection has cleared. These stowaways can stay with us for our entire lives but they can sometimes be roused from their slumber to infect again, especially if their host’s immune system becomes compromised. HIV patients, for example, often experience recurring infections. After decades of symptomless dormancy, HHV-6’s reawakening can be severe and debilitating.
Now, Jesse Arbuckle from the University of South Florida College of Medicine has uncovered the virus’s hiding place. Most herpesviruses just leave their genome as a ring of DNA floating about in infected cells. But HHV-6 is a far sneaker infiltrator. It actually shoves its genes into the genome of its host and it targets special structures call telomeres, which sit at the ends of our chromosomes. Telomeres are like the plastic tags at the ends of your shoelaces – they stop long strands of DNA from fraying at the ends, losing valuable information and becoming incorrectly entangled.
In Robert Louis Stevenson’s classic story, Dr Henry Jekyll drinks a mysterious potion that transforms him from an upstanding citizen into the violent, murderous Edward Hyde. We might think that such an easy transformation would be confined to the pages of fiction, but a similar fate regularly befalls a common fungus called Fusarium oxysporum.
A team of scientists led by Li-Jun Ma and Charlotte van der Does have found that the fungus can swap four entire chromosomes form one individual to another. This package is the genetic equivalent of Stevenson’s potion. It has everything a humble, Jekyll-like fungus needs to transform from a version that coexists harmlessly with plants into a Hyde-like agent of disease. In this guise, it infects so many plant species so virulently that it has earned the nickname of Agent Green and has been considered for use as a biological weapon. It can even infect humans.
These disease-making chromosomes came to light after Ma and van der Does sequenced the genome of a variety of F.oxysporum called lycopersici (or ‘Fol’), which infects tomatoes. Its genome was unexpectedly massive, 44% bigger than its closest relative, the cereal-infecting F.verticillioides. Looking closer, Ma and van der Does found that most of this excess DNA lies within four extra chromosomes, which Fol has and its relative lacks. Together, they make up a quarter of Fol’s genome.
Ma and van der Does demonstrated the power of this extraneous quartet by incubating a harmless strain of Fol with one that causes tomato wilt. Just by sharing the same space, the inoffensive strain managed to acquire two of the extra chromosomes found in the virulent one. And, suddenly, it too could infect tomatoes. In a single event, the fungus had been loaded with a mobile armoury and changed into a killer. It seems that the fungus needs just two of the four chromosomes to cause disease; the others probably act as accessories, boosting its new pestilent powers.
Millions of people in Latin America have been invade by a parasite – a trypanosome called Trypanosome cruzi. They are passed on through the bite of the blood-sucking assassin bug and they cause Chagas disease, a potentially fatal illness that affects the heart and digestive system. The infections are long-lasting; it can take decades for symptoms to show and a third of infected people eventually die from the disease. But T.cruzi does much more than invade our flesh and blood; it also infiltrates our genomes.
T.cruzi is unusual in that a massive proportion of its DNA, around 15-30%, lies outside of its main genome. These accessory sequences are stored in the form of thousands of interlinked DNA rings. In the parasite, these sequences are found in the mitochrondria – small structures that provide it with energy – but they have found a way to spread much further.
According to new research from Mariana Hecht and a team of Brazilian scientists, T.cruzi has the ability to inveigle its DNA rings into the genomes of those it infects. Once inside, the parasite genes can hop around, hitchhiking from one chromosome to another and leaving genetic chaos in their wake. They can even be passed on from one generation to the next. Hitching a ride aboard sperm and eggs, they can add themselves to the genomes of children, who’ve never been in direct contact with trypanosomes.
Hecht’s discovery suggests that T.cruzi is an unexpected source of genetic diversity in our species. It’s certainly not the only parasite to do this. Viruses have been infiltrating our genes since time immemorial and a massive part of our genome has a viral origin. These events, where viruses joined our family tree, provided raw material for natural selection. Some viral genes wreaked havoc by disrupting important genes, while others were eventually domesticated to act as helpful, even necessary, parts of our genome.
But T.cruzi is a different story. Despite its microscopic, single-celled nature, it’s a vastly complex creature compared to a simple virus. And it continues to breach our DNA today. Now that we’re getting technically better at detecting such “horizontal gene transfers“, we may find that many other parasites are also smuggling their genes into ours. In Hecht’s words, the “human population may be a patchwork of all the organisms to which it has ever been exposed.”
This article is reposted from the old WordPress incarnation of Not Exactly Rocket Science.
A humble species of fruit fly is the genetic equivalent of a Russian doll – peer inside its DNA and you will see the entire genome of a species of bacteria hidden within.
The bacteria in question is Wolbachia, the most successful parasite on earth and infects about 20% of the world’s species of insects. It’s a poster child for selfishness. To further its own dynasty, it has evolved a series of remarkable techniques for ensuring that it gets passed on from host to host. Sometimes it gives infected individuals the ability to reproduce asexually; at other times, it does away with an entire gender.
Now, Julie Dunning-Hotopp from the J. Craig Venter Institute and Michael Clark from the University of Rochester have found an even more drastic strategy used by Wolbachia to preserve its own immortality – inserting its entire genome wholesale into that of another living thing.
Among bacteria, such gene swaps are run-of-the-mill. Humans and other multi-celled creatures must (mostly) contend ourselves with passing our genes to our young but bacteria have no such limits. They can exchange genes as easily as we exchange emails and this free trade in DNA, formally known as ‘horizontal gene transfer’, allows them to swap beneficial adaptations such as drug resistance genes.
Gene transfer between bacteria and eukaryotes is rare but if any bacteria was well placed to do it, it would be Wolbachia. It infects the developing sex cells of its hosts and gets passed on from mother to child in the egg itself – a prime location for integrating its genes into those of the next generation.
Other labs had already managed to detect traces of Wolbachia genes in a species of beetle and a nematode worm. To discover the full extent of its genetic infiltration, Dunning-Hotopp and Clark decided to search for Wolbachia genes in a wide range of invertebrates.
Compare the elegant grace of a running wolf with the comical shuffle of a waddling dachshund, and you begin to understand what millennia of domestication and artificial selection can do to an animal. As dachshunds develop, the growing tips of their limb bones harden early, stunting their growth and leading to a type of dwarfism called chondrodysplasia. The same applies to at least 19 modern breeds including corgis, Pekingese and basset hounds, all of which have very short, curved legs.
These breeds highlight the domestic dog’s status as the most physically diverse of mammals. Now, a team of scientists led by Heidi Parker from the National Human Genome Research Institute have found the genetic culprit behind the stumpy limbs of all these breeds, and its one with surprising relevance for dwarfism in humans.
All cases of stunted legs in domestic dogs are the result of a single genetic event that took place early on in their evolution. Some time ago, a gene called FGF4 (short for fibroblast growth factor 4), which plays an important role in bone growth, was copied and reinserted into a new site in the dog genome. It’s this extra errant copy – a retrogene – that has retarded the growth of so many domestic breeds.
Parker’s team sequenced genes from over 835 dogs across 76 different breeds, including 95 short-legged individuals, and found a genetic signature unique to these stunted animals. This included a handful of genetic variants – each consisting of a single altered base pair or “DNA letter” – that were overrepresented in the short-legged breeds and that clustered in the same site. One of these variants was 30 times more common in the short-legged breeds than their long-limbed peers.
The team found that this mystery region exactly matched a gene called fibroblast growth factor (FGF4). That was puzzling, for FGF4 normally sits at a very different location, some distance away on the dog genome. In fact, Parker found that the short-legged breeds have two copies and the one associated with their abnormal growth has been inserted in an unusual site. Not only did all the stunted animals have this errant FGF4 gene, but 96% of them had two identical copies of it.
For centuries, farmers have been genetically modifying their plants without even knowing it. That’s the message from German scientists who found that grafting, a common technique used to fuse parts of two plants together, causes the two halves to swap genes with each other.
Grafting can involve fusing the stem of one plant (the scion) to the roots of another (the stock), or a dormant bud to another stem. There are many reasons for this – sometimes it’s the most cost-effective way of cultivating the scion, sometimes the stock has properties that the scion lacks including hardiness or sturdiness. The vessels of the two halves eventually merge but people have long believed that they keep their genetic material to themselves. It turns out they were wrong.
Sandra Stegemann and Ralph Bock from the Max-Planck Institute tested the theory by grafting two strains of genetically engineered tobacco plant. A Samsun NN strain had its main genome loaded with a gene that produced a glowing yellow protein, and another that made the plant resistant to the antibiotic kanamycin. The second Petit Havana strain was engineered to produce a glowing green protein, and be resistant to spectinomycin, another antibiotic. These genes were shoved into the genome of its chloroplast, the small structures that allow plant cells to photosynthesise and that contain their own separate genetic material.
Once the plants had merged, Stegemann and Bock found that the point of fusion was rife with cells that produced both glowing proteins and shrugged off both antibiotics. They cut slices from the plant and grew them in liquid that contained both kanamycin and spectinomycin for a month. While chunks that were taken from other parts of the plant fared poorly under these conditions, many of those from the graft site thrived, even producing fresh shoots.
The world of genetics is filled with stories that are as gripping as the plot of any thriller. Take the IRGM gene – its saga, played out over millions of years, has all the makings of a classic drama. Act One: setting the scene. By duplicating and diverging, this gene thrived in the cells of most mammals as a trinity of related versions that played vital roles in the immune system.
Act Two: tragedy strikes. About 50 million years ago, in the ancestors of today’s apes and monkeys, the entire IRGM cluster was practically deleted, leaving behind a sole survivor. Things took a turn for the worse – a parasitic chunk of DNA called Alu hopped into the middle of the remaining gene, rendering it useless. IRGM was, for all intents and purposes, dead and it remained that way for over 25 million years of evolution.
Act Three: the uplifting ending. The future looked bleak, but IRGM’s fortunes were revived in the common ancestor of humans and great apes. Out of the blue, a virus inserted itself into this ancient genome in just the right place to resurrect the long-defunct gene. A fall from grace, a tragic demise and an last-minute resurrection – what more could you ask for from a story?
This twisting tale lies hidden in the genomes of the world’s mammals and it was discovered and narrated by Cemalettin Bekpen from the University of Seattle. To reconstruct the evolutionary story of the IRGM gene, Bekpen searched for it in a variety of different species.
(Oh come on – you try to find an image to illustrate this story!)