New branches on the tree of life have just turned up in Africa. Some are cuter than others.
In Madagascar, our primate family was enlarged by two adorable species of mouse lemurs. Meanwhile, other scientists made an uglier discovery in the small country of Djibouti, in the Horn of Africa. They found a surprising diversity of bacteria that cause tuberculosis. When most people think about the joys of biodiversity, they probably don't think about the hidden expanses of parasites waiting to be discovered. But in cases such as this one, they can have a fascinating story to tell--one that may prove to be important to the welfare of our own species.
Tuberculosis is, like malaria and HIV, an infectious disease so vast in its success that it's hard to fathom. Every second someone somewhere in the world gets infected with the bacteria Mycobacterium tuberculosis, and each year TB kills about 1.75 million people. Many scientists have wondered how long these bacteria have been attacking the lungs of our ancestors. Hippocrates described cases that appear to be tuberculosis, and ancient mummies show signs of the disease. For earlier chapters in the evolution of TB, scientists have begun to turn to the bacteria's DNA.
The first studies pointed to a relatively recent origin of the disease. The bacteria that scientists sampled turned out to have nearly identical DNA. If a long time had passed since the common ancestor of living strains of TB, then they would have expected to find more mutations setting the strains off from one another. Instead, they esimated that a single successful ancestor gave rise to all current strains about 20,000 to 35,000 years ago.
But French researchers have found that people in Djibouti carry strains of TB that are significantly different than anything seen before. They have many more genetic differences than have been found in human TB strains from anywhere else in the world. Yet they are more closely related to other human TB than to the Mycobacterium species that infect cattle and other animals. The scientists then turned the mutations of the Djibouti strains into a molecular clock. They estimate that the ancestor of today's human TB existed some three million years. The results have just been published in the new open access journal PLOS Pathogens.
If tuberculosis was infecting our ancestors three million years ago, it was infecting early, small-brained hominids. All of the hominids known from that time lived in Africa, and hominids would not be found outside the continent for over a million years. Our own species is believed to have evolved much later in Africa, and to have spread to Asia and Europe roughly 50,000 years ago. So it's telling that all these ancient strains are found in Africa, not far from some of the richest lodes of hominid fossils in Ethiopia. The genetic diversity of these bacteria reflects the genetic diversity of living Africans.
Some diseases are new to our species, and some are old enemies. HIV probably made the jump from chimpanzee to human in just the past century. Like other emerging diseases, its evolution is a reflection of our times. It probably is the result of roads being pushed through African rain forests for logging, allowing hunters to kill chimpanzees and sell the meat to a growing, increasingly mobile society. Other diseases appear to have gotten their start thanks to earlier opportunities. Yersinia pestis, the cause of bubonic plague, rapidly emerged a couple thousand years ago, probably taking advantage of flea-infested rats that were thriving in cramped communities. Malaria appears to have emerged a few thousand years before that, when early African farmers spend their days clearing forests and creating lots of standing water in which mosquitoes could breed, only to go to bed nearby and become easy targets for the insects.
The new study suggests that tuberculosis came long before them. But it apparently has not been with us forever--or even for five or ten million years. For some reason it appeared three million years ago, and it's intriguing think why. The new paper doesn't hazard a guess, but I'm reminded of a similar study I came across while researching my book Parasite Rex. It has to do with tapeworms.
Today tapeworms have a life cycle that take them between pigs or cows and humans, where they can grow up to 60 feet long in their intestines. In the 1940s, researchers proposed that the three tapeworm species that infect humans descend from ancestors which pioneered our guts when cattle and pigs were first domesticated some 10,000 years ago. But a close look at their DNA showed otherwise. Scientists found that the closest relatives of human tapeworms did not make relatives of cows or pigs their intermediate hosts. Instead, they lived inside East African herbivores such as antelopes, and made he lions and hyenas that kill them their final hosts. The researchers then looked at the amount of variation between the DNA from different species of tapeworms. According to the agricultural hypothesis, that variation should have pointed to a common ancestor 10,000 years ago. But the scientists concluded that this common ancestor could have lived as long as a million years ago.
The scientists proposed that tapeworms began adapting to our hominid ancestors when they began putting more meat in their diet. By scavenging or hunting on the East African savannas, our ancestors became an attractive new habitat for the tapeworms, and new species evolved that were specialized only to live inside us. Only hundreds of thousands of years later did they make cows and pigs their intermediate hosts.
Given TB's similar antiquity, I wonder if it may have made a similar leap. Many closely relatives to Mycobacterium tuberculosis live in bovids--cows and their relatives--which hominids might have encountered as they began to scavenge meat. Could a sick wildebeest have been our patient zero?
Still, the question remains: why is so much TB diversity hiding out in Djibouti, while one branch seems to have exploded about 30,000 years ago and spread around the world, such that today it makes up the vast majority of TB cases? The paper's authors hazard that this lineage spread out of Africa with the migration of humans to other parts of the world. That makes sense up to a point. The bacteria that cause ulcers, Helicobacter pylori, spread this way--so faithfully in fact that it acts as a marker for human migrations to different parts of the world. But the new TB 30,000 years ago was able to spread much more aggressively than the other strains, which apparently are still restricted to the region where they've been for millions of years. It's hard to understand what sort of social or ecological change could have created the conditions that would favor such a superior bug.
Neverthless, it may be possible to pinpoint how this new lineage evolved into such a killer by comparing it to the older strains. If scientists can identify its special weapon, they might be able to figure out how to attack it with a drug. Here, then, is one potential benefit of exploring the diveristy of parasites: you can learn how to fight the really nasty ones.
They also warn that the assumption of stability of today's TB bacteria is not to be taken for granted; escape mutants are possible. TB is a tropical disease today, and likely started out that way. In between, though, TB came to be known as the white plague, on account of its association with the cities of Europe. In the 19th century there existed even virulent forms which killed people in less than a year. Unless our drugs and public health measures exterminated those forms once and for all, including even the genetic capacity of the bacteria to regenerate such varieties, shouldn't it be assumed that it could happen again? With several billion people infected, the chance for mutation favoring the virulent and efficiently spreading form would seem to be high. Tropical adapted populations are not specialized towards resisting TB, but towards resisting parasites against which, immediate hypersensitivity is the efficient response. Theory says that it has to be one or the other; or, if not, then science could be challenged to, and find, one individual who combines very high natural immediate and delayed hypersensitivity. That is, such that he could be genetically uncommonly resistant to both malaria and TB. This could be the difference between northern and tropical adapted populations, which has kept, and keeps, them distinct genetically.
Might the single strain of TB found worldwide relate to the idea that only a very few peole walked out of Africa to spread humans around the world? Maybe only one of the fellows around the campfire was sick when they left home?
Fascinating stuff, Carl. Do you have any similar information or ideas on the evolutionary history of the leprosy bacillus M. leprae, tuberculosis's close cousin?