Evolution of the CLTCL1 Gene Encoding CHC22 Clathrin Reveals Selection Influencing CHC22’s Role in Human Glucose Metabolism

摘要: CHC22 clathrin plays a key role in intracellular membrane trafficking of the insulin-responsive GLUT4 glucose transporter, and so post-prandial clearance from human blood. We performed population genetic phylogenetic analyses CLTCL1 gene, encoding CHC22, to understand its variable presence vertebrates gain insight into functional evolution. Analysis ~50 complete vertebrate genomes showed independent loss nine lineages after it arose gene duplication during emergence jawed vertebrates. All non-vertebrate eukaryotes considered here have retained parent CLTC CHC17 clathrin, which mediates endocytosis other housekeeping traffic pathways. Statistical analysis provides evidence strong purifying selection over timescales for CLTCL1, as well CLTC, supporting preserved functionality those species that CLTCL1. In humans chimpanzees, extensive allelic diversity was observed compared CLTC. all populations, two variants segregate at high frequency, resulting protein with either methionine or valine position 1316. The V1316 variant occurs only humans, but same site is polymorphic non-human primates well. archaic ancient bounded appearance derived allele 500-50 KYA. Balancing on high-frequency inferred, being more frequent farming, hunter-gatherer populations. Together these suggest undergoing related nutrient metabolism. Consistent this conclusion, we differences between their ability control traffic, predicted by structural modeling cellular dynamics variants.