Arginine residues at codons 112 and 158 in the apolipoprotein E gene correspond to the ancestral state in humans.
Level 5 - mechanism / opinion, no new human data
Level 5 by design analogy (comparative non-human genetic study; no human clinical trial data).
PubMed 7772071 · doi:10.1016/0021-9150(94)05402-5
What was done
Sequencing and analysis of codons 112 and 158 of the apolipoprotein E gene in 24 chimpanzees and individuals from multiple other non-human primate species to identify the ancestral apo E allele.
What was found
All 24 chimpanzees and the other primate specimens examined carried arginine residues at codons 112 and 158, matching the human apo E4 sequence. This indicates that apo E4 is the ancestral allele and that apo E2 and apo E3 mutations arose following the divergence of human and chimpanzee lineages.
Why it matters
This clarifies an evolutionary disagreement regarding the origin of human apo E isoforms, showing that the disease-associated apo E4 variant is the ancestral state.
Limits
The abstract describes a small sample of 24 chimpanzees and does not specify the sample sizes or specific species identities of the other primates tested. No human functional or longitudinal clinical data are evaluated in this study.
Cited by
- contradicts The ApoE4 allele was the primordial human isoform present during roughly 96% of hominid evolution, whereas chimpanzees lack ApoE4.