Ulcers of the World, Unite

There are six and a half billion human stomachs on this little planet of ours, and over half of them are home to a microbe called Helicobacter pylori. Scientists have known about the bacteria since the late 1800s, but it wasn't until the 1980s that Australian doctors noticed that H. pylori was in the stomachs of just about everyone with an ulcer. A swig of antibiotics turned out to be a great way to make ulcers disappear. Scientists have since demonstrated that H. pylori strikes up an uneasy truce with its human hosts. In most cases, H. pylori lives amicably in our stomachs. When the truce is broken, the microbe triggers a cascade of reactions that leave a stomach cratered. (The co-discovers of the H. pylori-ulcer link shared a Nobel prize in 2005, which I wrote about here.)

The discovery of H. pylori's role in ulcers attracted a huge amount of attention to the bug, and to its effects on different people. In the late 1990s Mark Achtman, a German microbiologist at the Max Planck Institut for Infectious Biology, began to gather strains of H. pylori from around the world. He and his colleagues compared the DNA from the strains to see how they were related to one another. They found something strange. Most of the H. pylori strains they collected in China and Japan appeared to be closely related to one another. Based on the diversity of these Asian germs, Achtman suggested they had arrived in the stomachs of early Homo sapiens that moved into Asia some 40,000 years ago.

Further research by Achtman and others indicated that other ethnic groups also carried their own strains of H. pylori. A debate then emerged about how germ and host got associated in this way. H. pylori is not like the flu, which can move between continents in a matter of days. Scientists don't know much about how it gets from stomach to stomach, but it seems to move mostly within families. So it would make sense that H. pylori's genealogy tracked the genealogy of its hosts. On the other hand, some critics have argued, H. pylori might be a recent arrival in our stomachs. If it jumped from animals to humans on several occasions in different parts of the world, it might have produced the same patterns seen by Achtman and others.

In this week's Nature, Achtman and his colleagues report the latest data on humans and their ulcer bugs. They argue that our histories are even more intimately wrapped together than previously thought...

Achtman now has H. pylori DNA from 769 people from 51 ethnic groups, spanning the world from the Finland to Samoa. He and his colleagues used this information to draw an evolutionary tree of the bacteria. They found that the bacteria fell into five major populations. (See figure b at the bottom of this post, which comes from the paper.) The scientists then made a careful study of where the people who carried strains from those five branches live, and used that information to determine where each branch originated. The deepest branch of the H. pylori tree originated in East Africa (Ancestral Africa 2, fig. g). Two younger branches are closely related to one another--one originating in west Africa (Ancestral Africa1, fig. f) and another in North Africa (AE2, fig. e). Another branch originated in India (AE1, fig. c) and is closely related to a branch found in East Asia and the New World (Ancestral EastAsia, fig. d).

This pattern, Achtman and his colleagues argue, bears a striking resemblance to the expansion of our own species over the past 100,000 years. A number of studies on human DNA (such as this one) indicate that Homo sapiens expanded from a small base in East Africa. At first they moved out through Africa, but then after about 60,000 years ago some populations pushed out into the Near East and then into Europe and Asia, and finally into the New World. The human genetic diversity found in Africa is greater than in the rest of the world, because humans have deeper roots there. Very small populations moved into other continents, and as a result, their genetic diversity is lower. In fact, the further away you go from Africa, the lower the genetic diversity gets. (Some scientists disagree, it should be pointed out.) Like humans, H. pylori has the greatest genetic diversity in Africa, and the further from Africa you go, the less diverse it gets.

Achtman and his colleagues built statistical models to figure out how best to explain the patterns they've found in H. pylori DNA. They conclude that early humans already carried H. pylori in their stomachs. (How bad their ulcers were the scientists don't say.) When people began expanding from East Africa, they took H. pylori with them, and ultimately they carried the bacteria across the world. The major branches of H. pylori that Achtman and his colleagues identified emerged during later population booms. The scientists can even detect the arrival of different strains of H. pylori in Europe as successive waves of human immigrants moved into the continent. Because H. pylori is so unadventurous when it comes to infecting new hosts, it has become a chronicler of our past.

H. pylori even has something to say about the ever-controversial matter of race. When scientists were first gathering up information on H. pylori, the geographical differences seemed stark. The bacteria in Europe were distinct from the ones in Asia or Africa. Scientists studying human DNA had much the same experience. They found that by examining certain genetic markers they could accurately predict which continent a person came from. But other scientists challenged these results. They argued that the data in the early studies were far from a representative sample of the world's human genetic diversity. These scientists put together their own collection of human DNA and concluded that the clusters blurred smoothly into each other.

H. pylori is now blurring as well. The chart in figure a below shows the different strains of H. pylori found in different human populations (the colors correspond to the branches of the tree in figure b). The people in different parts of the world have their own distinctive blend of bacteria, but for the most part one blend blends into the next, forming a continuum from Africa to the New World. Even in our ulcers, we are not so different after all.

(Paper link to come; doi:10.1038/nature05562)