A genetic phenomenon that allows for the selection of multiple genetic mutations that all lead to a similar outcome - a 'soft selective sweep' such as the ability to digest milk- has been characterized for the first time in humans.
This soft selective sweep was described in the population of Ethiopia by a team of geneticists from University College London, University of Addis Ababa and Roskilde University and reveals that individuals from the Eastern African population have adapted to be able to digest milk, but via different mutations in their genetic material.
Five different alleles are found in the Ethiopian population that cause adult lactase production, one of which is newly confirmed.
Transfection Experiment Showing the Effect of the −14009∗G Variant on the Enhancer Activity in Caco-2 Cells Promoter/enhancer constructs containing either the ancestral sequence, the −14009∗G variant, or the −14010∗C variant LCT enhancer sequence were transfected into Caco-2 cells together with a CMV-driven β-galactosidase expression plasmid. The cells were harvested and analyzed for luciferase and β-galactosidase activities 9 days after transfection. The luciferase expressions were corrected for transfection efficiency via the β-galactosidase activities. The −14010∗C construct was used as a positive control. The bar chart shows luciferase expression relative to the “promoter only” construct (lacking the enhancer) and the error bars represent SDs (n = 8). Both the −14009∗G and −14010∗C enhancer sequences lead to an increased luciferase expression, which is significantly different from the ancestral sequence (−14009∗C/−14010∗G; p = 0.000032 and 0.000038, respectively). Credit and link:
We need lactase when we are babies to digest our mother's milk, so in babies large amounts of lactase enzyme are expressed by our genes. When we are older we no longer rely on our mother's milk for essential nutrients, so in most humans manufacture of the lactase enzyme stops through de-activation of the corresponding gene.
However, subtle mutations in the regulatory region of the gene in some individuals cause lactase to carry on being expressed into adulthood. Different mutations are likely to affect lactase expression using slightly different mechanisms. This parallel selection of different gene mutations that have the same phenotypic effect - in this case lactase persistence - is known as a soft selective sweep.
Soft selective sweeps have not been so clearly described before in humans, one reason being that variations caused by soft selective sweeps are more likely to be caused by genetic mutations in regulatory sequences, rather than mutations found in coding regions of genes.
Most statistical methods that analyse genetic variation assume we are looking for only one variation as the cause of genetic adaptation. But, in soft selective sweep patterns, more than one genetic variation is selected in parallel, which makes them more difficult to detect.
Professor Dallas Swallow, from the UCL Department of Genetics, Evolution and Environment, senior author of the paper said, "Our genetic make-up determines our ability to digest milk into adulthood. Just over a third of the global population have inherited genes that allow us to make lactase, the enzyme that digests milk, as adults.
"This study shows that several different genetic changes that allow our bodies to make lactase have emerged independently. Changes to our lifestyle over the past 10,000 years -- including diet, altitude acclimatisation and infectious disease resistance -- will likely have caused many genetic adaptations of this kind."
Dr. Bryony Jones, also from the UCL Department of Genetics, Evolution and Environment, and lead author of the paper said, "Such variations have so far been very poorly studied and it will be important for them to be better characterized to understand better the relationship between historic adaptation and 21st century disease susceptibility."
Only in the last 5-10,000 years have humans started drinking the milk of other animals, following advances in our ability to herd animals. In times of plenty, being able to drink the milk of other animals would not have given a particular advantage to those with lactase persistence.
However, in situations where food sources became scarce, individuals capable of producing lactase as adults would be able to drink the milk of their animals, increasing their chances of survival.
Ethiopia has been subject to frequent droughts that contribute to famine. Individuals who can digest milk are more likely to increase their chance of survival under these conditions.
Jones explained, "Ethiopia has been a cross-roads of human migrations in the last five thousand years since the lactase persistence genes are likely to have come under selection. Our studies on other African and Middle Eastern populations show quite different geographic distributions, with overlap in Ethiopia, suggesting that their origins are all different, but determining where these were and how they spread is likely to be difficult."
Swallow concluded, "The combination of mutation, large effective population size, migration and selection has been shown to be important in generating this kind of pattern of diversity, namely parallel selection of multiple alleles of similar function, a so-called soft selective sweep."
Citation: Bryony L. Jones, Tamiru O. Raga, Anke Liebert, Pawel Zmarz, Endashaw Bekele, E. Thomas Danielsen, Anders Krüger Olsen, Neil Bradman, Jesper T. Troelsen, Dallas M. Swallow, 'Diversity of Lactase Persistence Alleles in Ethiopia: Signature of a Soft Selective Sweep', The American Journal of Human Genetics August 29 2013 doi:10.1016/j.ajhg.2013.07.008