Wednesday, May 30, 2007

Origins of infectious disease

You'll need a subscription (or visit to the local library), but there is a fascinating review from Jared Diamond and colleagues in a recent Nature: "Origins of major human infectious diseases".

One of the ideas espoused here is that there is a typical progression which human pathogens follow over long time periods. For example, Stage 1 means the pathogen is never naturally found in humans (i.e. this excludes laboratory exposures), whereas Stage 2 pathogens are found in humans but do not transmit from human-to-human. Stage 3 pathogens sometimes transmit human-human, but only for a few cycles, Stage 4 pathogens routinely transmit between humans but retain animal-human transmission routes and still are animal pathogens, and finally Stage 5 pathogens which are pathogenic only in humans.

There are lots of interesting evolutionary stories wrapped up in this model. For example, there is a group of viruses called simian foamy viruses which can be inferred to have speciated via the speciation of their host -- each virus species is specific to a single primate (and none infects humans).

One very interesting hypothesis in the review attempts to explain why during the European exploration & conquest of the Americas most diseases traveled from Old World to New World and few in the opposite direction. Of the 25 diseases explored, only 1 (Chagas) is clearly of New World origin with two others (TB & syphilis) still controversial and four others apparently untraceable to date (rotavirus, rubella, tetanus & typhus); the remaining 18 are all of Old World origin. The authors suggest two explanations. First, many of the diseases originated in domestic livestock; the Old World domesticated more species and tended to live in much closer proximity to their livestock. Second, many more tropical diseases originated in the Old World because Old World primates are genetically more similar to humans than New World primates.

The review also discusses some interesting open questions about pathogen emergence and evolution. Rubella virus has no known animal relative, but is thought to have emerged in humans as little as 11K years ago. Humans and chimps have distinctive Plasmodium species, but it is unknown whether these arose because of or after the human-chimp split. Whether TB and mumps have gone animal->human or human->animal remain open questions. To answer these questions, a lot of good old-fashioned virology needs to be done -- but I think there is also a huge opportunity to use next generation sequencing. By sequencing many Plasmodium species, a very detailed tree of their relationships might emerge and the genetic differences between them identified, ultimately leading to a mechanistic understanding of how each species has adapted to its host -- information that might be used to fight these nasty creatures. Metagenomic searches for viruses, perhaps using enrichment schemes or simply treating the host genome as a byproduct, might uncover new viruses.

A popular shibboleth of the anti-evolution crowd is that evolution is one of many (at best) equally valid theories for explaining the biological world. This review underlines the fallacy of this argument: hypotheses about evolutionary relationships and sequences are used as a framework to organize a lot of information, but also to generate new hypotheses for further exploration. It is this latter topic that is virtually never addressed by anti-evolution researchers; it is a conception of science which seems to perpetually evade their grasp.

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