Worldwide spatial genetic structure of angiotensin-converting enzyme gene: a new evolutionary ecological evidence for the thrifty genotype hypothesis

As JV Neel put forward the 'thrifty genotype' hypothesis, many researches tend to support this hypothesis involved in the regulation of energy balance. However, the phrase could equally well encapsulate broader traits and the forms of thrift should be multiple. In particular, genes involved in the regulation of water and sodium balance may also be excellent candidates as thrifty genes. In the present study, we selected the ancestral D allele of angiotensin-converting enzyme (ACE) gene, a key gene involved in water and sodium balance regulation, as a candidate to confirm the 'thrifty genotype' hypothesis in the framework of evolutionary ecology. On the basis of our compiled worldwide spatial genetics database of I/ D frequency of ACE gene and spatial climate database, using techniques of spatial statistics, we found (1) an obvious decreasing geographic genetic cline following the route of out-of-Africa expansion from East Africa, (2) a positive association between D allele and synthetic temperature factor, (3) and a negative relationship between D allele and synthetic humidity factor that covered most regions of the world, and obvious spatial dependence between D allele and these two climate factors followed the route of out-of-Africa expansion from Africa. This suggested that D allele of ACE gene is not only plastic in response to its environmental circumstance but also presents a striking geographic distribution showing the evidence of 'signatures of selection' by climate factors. Thus, it can be identified as a thrifty allele and could provide a new evolutionary ecological evidence for the 'thrifty genotype' hypothesis. European Journal of Human Genetics (2011) 19, 1002-1008; doi: 10.1038/ejhg.2011.66; published online 11 May 2011