One jump from chimps to humans – the origin of malaria

By Ed Yong | August 3, 2009 5:00 pm

Blogging on Peer-Reviewed ResearchSwine flu has made the world all too aware of the possibility of diseases making the leap from animal hosts to human ones. Now, we know that another disease made a similar transition from chimpanzees to humans, several thousand years ago. This particular infection is caused by a parasite, and a very familiar and dangerous one – Plasmodium falciparum, the agent responsible for malaria. 

Transmitted by the bite of mosquitoes, P.falciparum infects over 500 million people every year. Its closest relative is a related parasite, Plasmodium reichenowi, which infects chimpanzees. Leading an international research team, Stephen Rich from the University of Massachussetts has discovered that P.reichenowi is no mere relative – it’s actually P.falciparum‘s ancestor.

Rich compared the genes of the two species to build a Plasmodium family tree, which showed that all of the 133 known strains of P.falciparum, from all parts of the world, are united one a single branch on the P.reichenowi lineage. The stem of that branch represents a single event where P.reichenowi crossed the species barrier from chimps to humans.

The new study was possible because of eight newly collected samples of P.reichenowi from wild and captive chimps. Until now, only a single sample of this species had ever been isolated. Armed with fresh samples, the team focused their attention on three genes – cytB, clpC and 18s rRNA. They found that those of P.reichenowi are very varied, much more so than its genetically uniform cousin P.falciparum (even though we have over 16 times as many samples of the latter). Chances are that any two samples of P.reichenowi are more genetically distinct that either one is to P.falcarium.

Rich is sitting on the fence as to whether this means that the two species should actually be united as one. But he says that his results clearly rule out the idea that the two Plasmodium species have evolved separately from a common ancestor that itself infected the last common ancestor of chimps and humans. Instead, it’s more likely that the genetically uniform species, P.falciparum, evolved from the diverse one, P.reichenowi.

This isn’t a new idea.  As far back in the 1950s, the renowned anthropologist Frank Livingstone suggested that P.falciparum was an unwitting gift from chimpanzees. He reasoned that as agriculture increased the size of human societies, our encroaching presence in the dwindling forest homes of chimps provided many opportunities for a canny parasite to find fertile new infecting grounds.

Rich suggests that the jump from chimps to humans was driven by an evolutionary battle fought by Plasmodium parasites and their hosts at a genetic level. Part of Plasmodium‘s complicated life cycle involves infecting red blood cells, leading to one of the classic symptoms of malaria – anaemia. To infiltrate these cells, the parasites recognise a molecule on their surface called GYPA, using a sensor protein of its own called EBA-175.

In chimps, GYPA has a chemical cap called Neu5Gc and it’s this adornment that P.reichenowi recognises. Neu5Gc is one of a group of chemicals called sialic acids, and it’s produced from a related member called Neu5Ac; just one oxygen atom separates the two. The conversion process is driven by a gene called CMAH – a gene that works in chimps, but that’s been crippled in humans. As a result, our GYPA proteins are capped with Neu5Ac instead of Neu5Gc, which explains why P.reichenowi infects chimps but not us.

Some scientists think that a mutation that disabled the CMAH gene provided our early ancestors with temporary relief from P.reichenowi. By blinding the parasite to the GYPA protein, the mutation gave us a powerful advantage. But it wasn’t a permanent one; Plasmodium upped the stakes by evolving a version of the EBA-175 that was more relaxed in its choice of targets. This new weapon stuck to human proteins capped with Neu5Ac just as well as they did to chimp proteins capped with Neu5Gc.

This counter-move allowed the parasites to re-exploit their old victims and in time, one lineage – Plasmodium falciparum – developed a preference for the Neu5Ac target. Rich thinks that this final step occurred relatively recently, between five and ten thousand years ago, and gave the parasite an extreme ability to cause disease in humans. The benefits of this mutation allowed P.falciparum to quickly expand worldwide, which probably accounts for its lack of genetic diversity.

The fact that P.falciparumhas only once found a way to infect humans suggests that it’s very difficult for the parasite to evolve a protein arsenal that recognises a new type of sialic acid. The same could even be true for other unrelated infections, such as flu. Sialic acids are actually the big obstacle in the way of bird flu viruses spreading freely among humans. The cells of human and bird airways bear slightly different sialic acids on their surfaces and bird flu viruses, for the moment, have a preference for the bird version.

Reference: doi:10.1073/pnas.0907740106

More on malaria:

Genetically-modified mosquitoes fight malaria by outcompeting normal ones

Size matters for mosquitoes but medium-sized males do better


Comments (5)

  1. Rich

    Thanks for posting about this. I just heard about it on the radio and hoped you might have a post to clarify things. Thanks for not letting me down! The great evolutionary biologist William Hamilton died from malaria a few years back. Definitely a huge disease.

  2. Dale Hoyt

    What is P. falcarium? Is it a new name for P. falciparum?

  3. AriSan

    Re: Dale Hoyt
    P. falcicarium is not a new name for P. falciparum. It’ an unfortunate typographical error occurrred most prominently on the top of the diagramtic illustration. I saw not too long ago a person received an appreciative service award in a rather large public organization his name misspelled on the certificate. He was astonished encountering his misspelled name, and at first he felt that he should report immediately in a righteous indignation, but he calmed himself down, thinking that the administrators worked hard for the year end annual event. Not only that, but also they might be so embarassed that they could turn even to hate him for their self-preservation, knowing a crevice of the human nature. So, he took nearly a month of his time and reported about the error to the three top authorities, and they corrected the error without a hitch. It seems that the error can and does occur at all levels as even seen recently as small as a typographical error made a plane rider take a wrong plane and realized only after he arrived at an unintended location that there was only one letter ommission on his ticket purchase. We must simply check one more time always before we make submitions. I esteem the author Ed Yong greatly, and if the typo can happen even to him, I too must forgive my own not infrequent errors and feel not so embarrassed.
    AriSan

  4. AriSan

    LOL!
    I meant diagramatic, not “diagramtic” in my letter above.
    AriSan

  5. Ed Yong

    AriSan has just demonstrated Muphry’s Law – where anyone commenting on matters of spelling or grammar will themselves make mistakes of spelling and grammar. ;-)

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