Inuit metabolism revisited: what drove the selective sweep of CPT1a L479?

This article reassesses historical studies of Inuit metabolism in light of recent developments in evolutionary genetics. It discusses the possible selective advantage of a variant of CPT1a, which encodes the rate limiting enzyme in hepatic fatty acid oxidation. The L479 variant of CPT1a underwent one of the strongest known selective sweeps in human history and is specific to Inuit and Yu'pik populations. Recent hypotheses predict that this variant may have been selected in response to possible detrimental effects of chronic ketosis in communities with very low carbohydrate consumption. Assessing these hypotheses alongside several alternative explanations of the selective sweep, this article challenges the notion that the selection of L479 is linked to predicted detrimental effects of ketosis. Bringing together for the first time data from biochemical, metabolic, and physiological studies inside and outside the Inuit sphere, it aims to provide a broader interpretative framework and a more comprehensive way to understand the selective sweep. It suggests that L479 may have provided a selective advantage in glucose conservation as part of a metabolic adaptation to very low carbohydrate and high protein consumption, but not necessarily a ketogenic state, in an extremely cold environment. A high intake of n-3 fatty acids may be linked to selection through the mitigation of a detrimental effect of the mutation that arises in the fasted state. The implications of these conclusions for our broader understanding of very low carbohydrate metabolism, and for dietary recommendations for Inuit and non-Inuit populations, are discussed.

Surface swarming motility by Pectobacterium atrosepticum is a latent phenotype that requires O antigen and is regulated by quorum sensing.

We describe a previously cryptic phenotype associated with the opportunistic phytopathogen Pectobacterium atrosepticum (Pca): surface swarming. We found that when Pca was spotted onto plates containing <0.5% (w/v) agar, the culture produced copious amounts of extracellular matrix material containing highly motile cells. Once produced, this 'slime layer' spread rapidly across the plate either as an advancing front or as tendrils. Transposon mutagenesis was used to identify mutants that were affected in swarming. Hypo-swarmer mutants mostly carried insertions in a horizontally acquired island (HAI5), which encodes a cluster of genes involved in O antigen biosynthesis. Hyper-swarmer mutants mostly carried insertions in hexY, a known antagonist of the class I flagellar master regulator, FlhD4C2. In addition, we found that the nucleoid protein, histone-like nuclear structuring protein 2 (H-NS2), also regulated swarming behaviour. A mutant in which hns2 was overexpressed displayed a hyper-swarming phenotype, whereas a mutant in which the hns2 ORF was inactivated had a hypo-swarming phenotype. Swarming was also regulated by quorum sensing (QS) and by the carbon source being utilized. We show, using a range of epistasis experiments, that optimal swarming requires both motility and O antigen biosynthesis, and that H-NS2 and QS both promote swarming through their effects on motility.