Paleofantasy: What Evolution Really Tells Us about Sex, Diet, and How We Live (32 page)

A 2010
New York Times
article by Nicholas Wade was headlined “Scientists Cite Fastest Case of Human Evolution.” Everybody loves the winner of a race, and here the winners were the high-altitude natives of Tibet, where life at 13,000 feet above sea level does not produce the usual symptoms of mountain sickness, a malady arising from the body’s unsuccessful attempt to counteract the lack of oxygen in the air. In non–mountain dwellers, the body compensates for low oxygen levels by increasing its production of red blood cells. Red blood cells are in turn the carriers of hemoglobin, the molecule that binds to oxygen and carries it to the organs and tissues. The increase in red blood cells thickens the blood and causes a number of health problems, ranging from headaches and insomnia to difficulty breathing and brain swelling, and in the long term it can reduce fertility and cause women to have smaller babies.

The Tibetans, however, seem to have overcome these difficulties. Unlike other people, they do not have an elevated amount of hemoglobin in their blood, but instead have higher breathing rates at rest without experiencing any ill effects. In contrast, when Han Chinese, the majority ethnic group in China, live at the same high altitude as the Tibetans, they exhibit signs of the kind of chronic mountain sickness that most Westerners would experience under similar conditions. How do the Tibetans cope, and why the difference between the two groups of people?

Human beings evolved more or less at sea level, and the extreme environments of high mountains were colonized much more recently, with current estimates ranging from 11,000 years ago for the Andes and perhaps 3,000–6,000 years ago for the Tibetan Plateau. Interestingly, Andean natives do not show the higher respiratory rate seen in Tibetans, and they also have high hemoglobin concentrations in their blood, in contrast to the mountain people of Tibet. Although both groups of people thrive at high altitudes, they seem to have different solutions to similar problems.

The genetics of the Andean natives have not been well studied, but independent groups of researchers recently demonstrated that Tibetans exhibit unique genetic adaptations to living at high elevations. In the first example, a group of scientists from China and the United States scanned fifty unrelated individuals from Tibet and compared their genomes with those of forty people of ethnic Han heritage.
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Using a different approach, a team led by Tatum Simonson of the University of Utah and RiLi Ge of Qinghai University in China looked for genes in Tibetans, Chinese, and Japanese that seemed to have been subject to selection for the ability to deal with low oxygen levels.
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Variants of a gene catchily named hypoxia-inducible factor 2-alpha, or
HIF2-
å
for short, as well as two genes that modify its effects, were associated with a lower concentration of hemoglobin in the blood of the Tibetan highlanders. Having lower levels of hemoglobin means that the Tibetans avoid the problems that come along with more red blood cells.

If avoiding the overproduction of red blood cells is more advantageous, why doesn’t the human body do that naturally, rather than vainly ramping up hemoglobin levels, which creates more problems than it solves? The answer illustrates the tinkering nature of evolution that I mentioned in Chapter 6. According to Jay Storz from the University of Nebraska, increasing one’s hemoglobin concentration in response to decreased oxygen levels may have evolved to counteract anemia, which also causes a decrease in the amount of oxygen available to the body.
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But altitude sickness and anemia differ in a crucial characteristic: the latter can be somewhat ameliorated by increasing hemoglobin concentration because it stems from an inability of the blood itself to transport oxygen. With altitude sickness, the blood is less saturated with oxygen because less oxygen is available in the air to begin with, and hence increasing hemoglobin concentration actually prevents oxygen from reaching tissues.

Evolution, of course, doesn’t know why the blood levels of oxygen have diminished; in our ancestral sea-level environment, a rule of thumb that says, “When oxygen is low, increase hemoglobin” would work perfectly well. In the Tibetans, however, an individual who exhibited a mutation that did not provoke such a response when oxygen levels were low would actually survive and reproduce better than the more usual variant would. This, of course, is exactly what appears to have happened. In the Andes, the mutation may not have arisen, and the two populations of mountain dwellers could differ simply because different raw material was available for selection to act upon.

The media made much of the “fastest evolution ever” sound bite, in the process highlighting discussions of exactly how long ago the Tibetan Plateau was populated. If the number of years comes in at higher than 7,500, then the prize will go to the evolution of lactase persistence, but if it is the 3,000 or so postulated by the geneticists, then Tibetan altitude adaptation will be the clear winner. Archaeologists, who rely on evidence such as preserved hand- and footprints, remains of tools, or butchered animal bones, tend to favor a longer settlement history, but the matter is still not resolved. Among geneticists, a few thousand years more or less is well within the bounds of their estimation, so they are not much bothered either way.

Earwax, and sweeping through time

Regardless of who wins the fastest-evolution race, the number of demonstrations of recent evolution and selection in the human genome is mounting: lactase persistence, amylase starch digestion, malaria resistance, adaptation to high altitude. We could keep adding to the list, and we are (wait till I get to the earwax), but now that the human genome has been sequenced and it is possible to analyze large sections of DNA at a time, many scientists are taking a different approach. By examining sequences that appear to have been inherited as a block, it is possible to detect the genes that have been subject to recent selection.

What’s more, scientists can often distinguish between so-called positive and negative selection. While natural selection results in individuals predominating if their genes are more suited to the environment, that process can happen in either of two ways. With negative selection, new harmful mutations are culled from the genome, changing the gene frequencies in the population (hence causing evolution), but doing so by subtraction, not addition. Negative selection is the reason that many of the genetic regions associated with manufacturing proteins are so similar among species: making proteins is fiddly work, and small deviations can be disastrous, so any mutations that altered the ancestral plan would likely not survive. Negative selection is the Grim Reaper of evolution, relentlessly removing, according to recent studies, up to three-quarters of the mutations that arise, though most of that elimination occurs very early in life, even before a fertilized egg implants in the uterus.

Positive selection seems more creative and somehow cheerful, acting to increase the frequency of a new or previously rare mutation that renders its bearer more likely to survive and reproduce. As a 2007 paper by geneticists from Cornell University and the University of Copenhagen notes, positive selection has received a great deal of interest from scientists “because it provides the footprints of evolutionary adaptation at the molecular level.”
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We can detect selection by looking for so-called selective sweeps, areas in the genome where chunks of DNA appear to have been inherited
en masse
. I discussed the basic idea in Chapter 5, where I pointed out that it is possible to determine whether genes associated with digesting different foods are found in people whose heritage came from various parts of the world. When selection favors a certain gene, its neighbors are carried along with it, and the resulting block of DNA becomes more homogeneous than expected because the nearby genes are hitchhiking along. By determining the likely function of genes caught up in such selective sweeps, it is possible to see which genes are subject to more rapid evolution. In the figure shown here, each person has a different set of genes, which would ordinarily be recombined in succeeding generations. But because the language gene 5 is advantageous, the surrounding genes will also all be the same following selection.

The aftermath of a selective sweep. All of the people have different gene combinations that they would ordinarily pass on to their descendants. But if variant 5 is favored, it will rapidly appear in a disproportionate number of people in the next generations, accompanied by the genes that are close to it, even if those genes are not themselves advantageous.
(Adapted from a figure by Rebecca Cann)

Searches for selective sweeps have yielded a number of areas in the genome where selection seems to have acted relatively recently, meaning within the last few tens of thousands to hundreds of thousands of years. Many of those rapidly evolving genes are associated with disease resistance, as I noted in Chapter 9. The “arms race” that occurs as a pathogen’s genes evolve new ways to get around the defenses of the host, and the host counters with ever-more effective defenses, provides a good proving ground for advantageous gene variants.

A recent survey of African American, European American, and Chinese gene samples by many of the same researchers who wrote the review mentioned earlier found evidence of selective sweeps at 100 regions in the genome that were located near a gene with a known function.
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Skin pigmentation, odor detection, nervous system development, and immune system genes appeared to show the most signs of recent evolution. In addition, the scientists found that the Chinese and European American populations showed more selective sweeps than did the African American population. This result is expected if the humans who left Africa experienced new selective pressures as they colonized environments with climates, foods, and diseases that were radically different from those of their homeland. The new environments provided strong selection and hence sweeps should be easier to detect. In all, the researchers concluded that as much as 10 percent of the human genome shows the effects of such selective sweeps.

Although enthusiasm for the search for selective sweeps has been high for the last several years, a few scientists have sounded a note of caution. Jonathan Pritchard and Anna Di Rienzo titled a 2010 paper “Adaptation—Not by Sweeps Alone” to argue that the old-fashioned way to detect selection, à la the Framingham study approach, may have been overlooked in the frenzy to use shiny new genomic tools. They do not suggest a Luddite approach to genetics, but rather point out that many evolutionary changes occur through the interaction of many genes at different places throughout the genome. Therefore, simply looking for places in the genome where blocks of genes have been inherited together risks missing the more subtle, but no less rapid, changes that have happened over time.

Taking matters further, a group of scientists from Chicago, Israel, and the United Kingdom reanalyzed the DNA sequences of 179 people from four populations, with the aim of determining whether the low genetic diversity surrounding selected genes was really a good indicator of a selective sweep.
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The rationale behind searching the genome for the areas of DNA that are inherited as a package is, as I described earlier, that the accompanying genes get swept along with the gene that’s being selected, yielding areas with less variability than one would expect. But how much variability does one expect in the first place, and could other mechanisms account for patches of low diversity in the genome?

The scientists, led by Ryan Hernandez, now an assistant professor at UC San Francisco, discovered that the low-diversity segments were actually distributed in several places throughout the genome, not just surrounding particular types of genes. The hitchhiking genes, in other words, were not necessarily with the same driver that had picked them up on the highway. In addition, although the geographic variation in gene frequencies was still present in the samples studied by Hernandez and colleagues, so that African samples differed from European samples, the differences were often subtle, and a matter of degree rather than kind. The researchers don’t deny the occurrence of selective sweeps, but along with Pritchard and Di Rienzo, they caution against attributing too much importance to this mechanism, and against assuming that such sweeps were the main way in which human evolution occurred.

Usually, even when a gene or stretch of DNA that has recently changed frequency in a population can be identified, the exact function of that gene remains a mystery. It may be possible to say that the gene is part of an immune response, or that it is important in protein synthesis, but more specific examples, aside from the oft-mentioned lactase persistence and a few others, tend to be thin on the ground. A recent exception occurred in 2006, but the assignment of a small piece of DNA to its effect in the human body may leave people less than overwhelmed: a team of Japanese researchers identified the tiny genetic change responsible for the type of earwax a person harbors.
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