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

Abstract

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.

Race, regionality and pre-diabetes in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study

“…Proponents of the thrifty gene hypothesis have examined other genes that provide support to the thrifty gene hypothesis for diabetes prevalence. The ancestral hypertension sensitive gene has been proposed by some researcher to be a thrifty gene (Li et al, 2011). Researchers have investigated the evolutionary ecology of the hyper-tension sensitive gene's (ancestral D allele of angiotensin-converting enzyme [ACE]) propensity for water and sodium retention and subsequently blood pressure regulation.…”

“…The researchers concluded that the gene's sodium/water balance properties were directly related to the body's physiologic sweat response in the hot and arid climate of Africa. As descendants moved from the hot and arid climate of Africa the salt-sensitive D allele ACE gene became deleterious (Li et al, 2011). The thrifty gene hypothesis has also been proposed as a plausible explanation for the increased body mass index observed in Polynesian populations.…”

Characterization of the Relationship between APOBEC3B Deletion and ACE Alu Insertion

“…The deletion allele was found to be associated with higher plasma ACE concentrations; that is, the average plasma ACE level of persons with the various genotypes follows the order DD>ID>II [1]. The I/D genotype distribution of ACE shows apparent variations among different ethnic populations throughout the world [8]. A number of research papers have reported a significant association between ACE I/D polymorphism and a series of diseases, including hypertension, type 2 diabetes, cardiovascular disease, kidney disease, cancer, and obesity [2]–[7].…”

“…Insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene is an important genetic marker that has been used in numerous studies [1]–[8]. ACE is a key enzyme of the renin-angiotensin system (RAS) and is widely distributed in human tissues, including the vascular endothelium, intestinal epithelium, kidney, lung, and testes [9], [10].…”

“…The A3B genotype distribution in world populations indicates a weak selection for the deletion [21]. In addition, the ACE D allele also presents a striking geographic distribution, showing evidence of “signatures of selection” that follows the out-of-Africa route [8].…”