GENETIC changes that helped our ancestors survive the cold may be protecting modern populations against diseases such as Alzheimer鈥檚 and Parkinson鈥檚.
This hypothesis has emerged from a reconstruction of DNA mutations that occurred during our species鈥� march out of Africa around 100,000 years ago. It illustrates how understanding our evolutionary past can shed light on patterns of disease today.
鈥淥ur evolutionary history has a huge effect on modern health,鈥� says Douglas Wallace at the University of California in Irvine, who led the research. His team studied mitochondrial DNA sequences from populations across the globe. By matching alterations in the DNA to past evolutionary events they were able to pick out changes that may have helped our ancestors adapt to new climates. These mutations are of a kind that could predispose people to some diseases while protecting them from others.
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In mitochondria, cells鈥� energy-producing organelles, there is a trade-off between generating heat and making energy-rich molecules to supply other parts of the cell. Any genetic changes that increase heat production lead to less energy being available from each calorie in food.
By comparing 1125 sequences from mitochondrial DNA, the team reconstructed many of the genetic changes that have occurred since humans left Africa. It turns out that such mutations almost always occurred at the base of human lineages that colonised a new region. Wallace suggests that as populations migrated northwards, for example, the trade-off would have swung in favour of heat at the expense of efficiency, because colder climates would favour individuals that are most efficient at generating body heat (Science, vol 303, p 223).
But fiddling with the efficiency of mitochondria has other consequences, too. Mitochondria also produce highly reactive free radicals which damage DNA and proteins and have been implicated in ageing and neurodegenerative diseases. People whose mitochondria are less efficient at producing energy-rich chemicals also make fewer free radicals, so are less susceptible to Alzheimer鈥檚 and Parkinson鈥檚.
This would have been largely irrelevant to early humans who did not live long enough to develop neurodegenerative conditions. But it may have a profound impact now. On the flip side, people from cold-adapted lineages are more likely to suffer from energy-deficiency diseases such as Wolfram syndrome.
The team鈥檚 ideas are backed by earlier research. An Italian study published in 2001, for example, showed that healthy centenarians in Italy have a high incidence of a certain mutation in the cytochrome B gene, which is part of the energy-production machinery (FASEB Journal, vol 13, p 1532). Remarkably, Wallace鈥檚 study has found that this lineage, and another found in Europe which is also associated with longevity, called the UK mitochondrial lineage, have the same mutation. Yet the two mutations occurred independently of each other.
Wallace鈥檚 study goes against the traditional view that the spread of most mitochondrial mutations occurs by chance, says Alan Cooper, head of the Ancient Biomolecules Centre at the University of Oxford. He suggests that testing fossil human or Neanderthal DNA might help to pin down the precise timing of the changes. It would also help bolster Wallace鈥檚 hypothesis that such mutations helped equip ancient humans for the cold.