Scholars who retain an interest in Dr. James V. Neel’s thrifty gene hypothesis have been disappointed time and again, by finding candidates that did not measure up to the criteria. “The evidence for a specific gene alteration generating a thrifty genotype is inconclusive,” writes oncologist Ajit Venniyoor, who then proposes PTEN as the gene that appears to influence metabolism, cancer, and reproduction.
What those areas have in common is, they become “deranged in obesity and insulin resistance.” The author goes on to explain that the gene is “like a metabolic rheostat” which “fixes’ the metabolic capacity of the organism periconceptionally to a specific postnatal level of nutrition, but when faced with a discordant environment, leads to obesity related diseases…” It sounds like what Dr. Neel was talking about, to the point where Dr. Venniyoor concludes that “PTEN is the primary thrifty gene.” Here is the extended, technical reasoning:
Epigenetic modification (methylation) of PTEN promoter suppresses the expression of the gene proportional to availability of nutrients (protein, and possibly choline). This sets the metabolic capacity and adapts the fetus to nutrition availability in post natal environment. A mismatch with calorie abundance results in efficient storage and limited expenditure and causes obesity, metabolic syndrome and cancer.
This gene can make good use of limited energy to grow and reproduce. It arranges for the safe storage of excess energy, and “multiple lines of evidence suggest that PTEN does this brilliantly.” In short, it fits the thrifty gene job description.
Skeptics say that a gene or genes like the one Dr. Neel visualized would eventually lead to the extinction of humans with non-thrifty genotypes. We haven’t all died yet, but an awful lot of metabolic diseases are looking to kill us, and the thrifty genotype hypothesis is seen as providing an explanation for that. Author Kian-Peng Goh points out the disadvantage such a genotype would suffer when faced with “dissonance between ‘Stone Age’ genes and ‘Space Age’ circumstances”:
However, no thrifty genes or variants have been identified to date and only approximately 20%-30% of the population is obese, although one would expect a proportion close to 100% since according to this hypothesis, everyone should have thrifty genes by now. Consequently, the debate on thrifty genes still rages on.
Your responses and feedback are welcome!
Source: “PTEN: A Thrifty Gene That Causes Disease in Times of Plenty?,” FrontiersIn.org, 06/05/20
Source: “Gene–Environment Interaction in the Pathogenesis of Type 2 Diabetes,” ScienceDirect.com
Image by Diego Mundarain/CC BY-ND 2.0