Diet and mtDNA selection

Lowell and Shulman (2005) report on the possible links between the metabolic defects underlying type 2 diabetes and mitochondrial dysfunction. These links go through two channels. In the first, decreases in mitochondrial activity in older adults were associated with higher levels of triglycerides in muscle and liver tissue as well as greater insulin resistance in muscle tissues. This observation supports the hypothesis that mitochondrial oxidation of fatty acids becomes less effective in older individuals, "which in turn lead[s] to increases in intracellular fatty acid metabolites...that disrupt insulin signalling'' (384). It is not clear whether this alteration is due to mitochondrial loss or reduction in function, but the authors suggest based on several other studies that there may be a connection with an accumulation of mtDNA mutations in elderly individuals.

The second channel involves the secretion of insulin by beta cells in the pancreas. In individuals with insulin resistance, the body can sometimes adapt to greater insulin requirements by ramping up the production of insulin in the pancreas. This pathway of insulin secretion depends on the mitochondrial metabolism of the beta cells. This connection has been established by the fact that mtDNA mutations can induce hereditary diabetes by causing beta cell dysfunctions.

Changes in fatty acid metabolism would likely be necessary at least twice during the evolution of early humans. With a dietary change toward greater meat eating, either at the origin of the habilines or that of early large-bodied Homo, a greater dietary availability of animal fats and focus on those resources might well have driven a selective change in digestive metabolism. The highly meat-dependent diet of people in the northern extremes, including the Neandertals, would have focused most digestive and metabolic resources toward animal protein and fat, and might have required additional changes. Then, a shift from a Neandertal-like diet to a broader diet during the Upper Paleolithic might well have required an additional change. It is not obvious that these shifts occurred globally, and there may well have been regional differences in meat digestion and metabolism based on local selection due to dietary differences. If the mtDNA was one of the genetic regions affected by such selection, there may well have been a very complex pattern of evolutionary changes in this molecule across the human lineage. This could account for changes within the Neandertal lineage, as well as the apparent replacement of Neandertal mtDNA by a type prevalent in recent humans.

References:

Lowell BB and Shulman GI. 2005. Mitochondrial dysfunction and Type 2 diabetes. Science 307:384-387.