Thr92Ala polymorphism in the type 2 deiodinase gene: an evolutionary perspective

Area of Science:

• Human evolution
• Genetics
• Endocrinology

Background:

• Thyroid hormones, particularly triiodothyronine (T3), play a role in human evolution.
• T3 is derived from thyroxine (T4) via the deiodinase 2 (D2) enzyme, encoded by the DIO2 gene.
• The DIO2 polymorphism rs225014 (A/G) affects T3 levels, with the G allele (Ala92) linked to lower T3 in deficient patients.

Observation:

• Archaic humans (Neanderthals, Denisovans) were homozygous for the G allele at rs225014, encoding Alanine (Ala92).
• This suggests these hominins had reduced D2 activity and potentially lower T3 levels.
• Their hunter-gatherer diet, low in carbohydrates, may have reduced the need for high circulating T3.

Findings:

• The A allele (Thr92), associated with higher T3, first appeared in Anatomically Modern Humans during the Upper Pleistocene.
• This variant has been conserved through the Neolithic period.
• The A allele was positively selected, likely conferring a survival advantage with the advent of agriculture.

Implications:

• The study provides an evolutionary perspective on the p.Thr92Ala variant of D2.
• Dietary shifts and the development of agriculture influenced the selection of DIO2 variants in human populations.
• Understanding these genetic adaptations is crucial for comprehending human adaptation to changing environments and diets.