Tibetans live at altitudes of 13,000 feet, breathing air that has 40 percent less oxygen than is available at sea level, yet suffer very little mountain sickness.

The reason, according to a team of biologists in China, is human evolution, in what may be the most recent and fastest instance detected so far. Comparing the genomes of Tibetans and Han Chinese, the majority ethnic group in China, the biologists found that at least 30 genes had undergone evolutionary change in the Tibetans as they adapted to life on the high plateau. Tibetans and Han Chinese split apart as recently as 3,000 years ago, say the biologists, a group at the Beijing Genomics Institute led by Xin Yi and Jian Wang. The report appears in Friday’s issue of Science.

If confirmed, this would be the most recent known example of human evolutionary change. Until now, the most recent such change was the spread of lactose tolerance — the ability to digest milk in adulthood — among northern Europeans about 7,500 years ago. But archaeologists say that the Tibetan plateau was inhabited much earlier than 3,000 years ago and that the geneticists’ date is incorrect.

When lowlanders try to live at high altitudes, their blood thickens as the body tries to counteract the low oxygen levels by churning out more red blood cells. This overproduction of red blood cells leads to chronic mountain sickness and to lesser fertility — Han Chinese living in Tibet have three times the infant mortality of Tibetans.

The Beijing team analyzed the 3 percent of the human genome in which known genes lie in 50 Tibetans from two villages at an altitude of 14,000 feet and in 40 Han Chinese from Beijing, which is 160 feet above sea level. Many genes exist in a population in alternative versions. The biologists found about 30 genes in which a version rare among the Han had become common among the Tibetans. The most striking instance was a version of a gene possessed by 9 percent of Han but 87 percent of Tibetans.

[NYTimes]

The connection between gut bacteria and obesity has gained some weight, with new findings demonstrating links in mice among immune-system malfunction, bacterial imbalance and increased appetite.

Mice with altered immune systems developed metabolic disorders and were prone to overeating. When microbes from their stomachs were transplanted into other mice, they also become obese.

“This supports the notion that some of the increase in obesity may be because of changes to gut bacteria,” said Andrew Gewirtz, an Emory University immunologist and co-author of the study, published March 4 in Science.

The findings are the latest in a growing body of research about the long-unappreciated role of bacteria in our bodies. Bacterial cells actually outnumber human cells in the body: From an outside perspective, people are not so much individual organisms as symbiotic human-bacteria collectives.

Disturbances to internal bacteria have been linked to asthma, cancer and many autoimmune diseases. Gut flora have also been linked to obesity. In 2006, researchers led by Washington University microbiologist Jeffrey Gordon documented bacterial changes in the stomachs of mice who became obese on high-fat diets.

When transplanted, their gut bugs turned other mice obese, suggesting that altered bacteria were not only an effect of weight gain, but a cause. The Science findings complement those, but also emphasize the immune system’s role and the possibility of appetite change.

“The reason why people are eating too much may not simply be because unhealthy food is cheap and available, but that their appetites may be driven by changes in gut bacteria,” said Gewirtz,

In the Science study, Gewirtz and Emery microbiologist Matam Vijay-Kumar studied a strain of mice deficient in TLR-5, a gene that’s required for immune systems to recognize many types of bacteria.

They found that TLR-5–deficient mice are about 20 percent heavier than regular mice. They overeat, have high blood pressure and high cholesterol, and are insulin-resistant. In humans, that constellation of conditions is known as metabolic syndrome, and in both people and mice leads to obesity and diabetes.

Earlier research had found unusual patterns of bacteria in the guts of those mice. When the researchers transferred bacteria from the stomachs of TLR-5–deficient mice to mice without gut bacteria, the recipients started to eat more, and soon developed metabolic syndrome.

“It’s a really exciting paper. It confirms and supports a lot of the findings we’ve had, and adds in the interaction between gut bacteria and the immune system,” said Peter Turnbaugh, a systems biologist who moved from Jeffrey Gordon’s lab to Harvard University. “It’s been thought for a long time that maybe the immune system is an important regulator of what’s in the gut.”

How gut bacteria produce metabolic changes isn’t known. They may process nutrients directly, or alter the activity of metabolism-regulating genes.

Mice used in the research are not considered exact models of bacteria and obesity in humans. Instead they’re models of these sorts of relationships likely to exist in people. Gewirtz’s team is now investigating whether people with metabolic syndrome have unusual gut bacteria.

The findings don’t suggest obesity is literally contagious, said Turnbaugh. But they do raise the possibility of altering the composition of gut bacteria, either directly or — more realistically — by learning what sort of environmental and lifestyle factors produce obesity-causing bugs.

One possible culprit is the ubiquitous presence of antibiotics, both prescribed and in the environment, said Gewirtz.

“It may be that an unintended consequence of this has been the upset of bacterial populations that are promoting obesity and metabolic syndrome,” he said.

Image: Left, regular and TLR-5–knockout mice. Right, a comparison of their insulin-producing islet cells./Andrew Gewirtz

In 1988 an associate professor started growing cultures of Escherichia coli. Twenty-one years and 40,000 generations of bacteria later, Richard Lenski, who is now a professor of microbial ecology at Michigan State University, reveals new details about the differences between adaptive and random genetic changes during evolution.

Sequencing genomes of various generations of the bacteria, which had been frozen periodically over the years, Lenski and his team found that adaptive and random genomic changes don’t necessarily follow the same patterns. Rather than a plodding equilibrium, even in a consistent environment, the interplay between these two kinds of genomic changes “is complex and can be counterintuitive,” Lenski said in a prepared statement.

Early changes in the bacteria appeared to be largely adaptive, helping them be more successful in their environment. “The genome was evolving along at a surprisingly constant rate, even as the adaptation of the bacteria slowed down,” he noted. “But then suddenly the mutation rate jumped way up, and a new dynamic relationship was established.”

By generation 20,000, for example, the group found that some 45 genetic mutations had occurred, but 6,000 generations later a genetic mutation in the metabolism arose and sparked a rapid increase in the number of mutations so that by generation 40,000, some 653 mutations had occurred. Unlike the earlier changes, many of these later mutations appeared to be more random and neutral.

The long-awaited findings show that calculating rates and types of evolutionary change may be even more difficult to do without a rich data set. “The fluid and complex coupling observed between the rates of genomic evolution and adaptation even in this simplistic system cautions against categorical interpretations about rates of genomic evolution in nature without specific knowledge of molecular and population-genetic processes,” the paper authors wrote.

Such detailed pictures of mutation rates have been made possible since the advent of rapid genome sequencing. “It’s extra nice now to be able to show precisely how selection has changed the genomes of these bacteria, step by step over tens of thousands of generations,” Lenski said.

The new data “beautifully emphasize the succession of mutational events that allowed these organisms to climb toward higher and higher efficiency in their environment,” Dominique Schneider of the Université Joseph Fourier in Grenoble, France, and a coauthor on the paper, said in a prepared statement. The paper, published online today in Nature, also happens to come 150 years after Charles Darwin published his Origin of Species. (Scientific American is a part of the Nature Publishing Group.)

The findings might eventually help scientists better understand mutations in human diseases and infections. “Cancer progression is a fundamentally similar evolutionary process,” Jeffery Barrick, a postdoctoral researcher at the lab and lead author of the paper, said in a prepared statement. And although the research team will continue to study the progress of the minute bacteria in search for more answers, he added: “We know an astounding amount about the details of evolution in these little Erlenmeyer flasks.”

By Katherine Harmon