Evolution of human apolipoprotein E (APOE) isoforms: Gene structure, protein function and interaction with dietary...

Area of Science:

• Evolutionary biology
• Molecular biology
• Human genetics

Background:

• Apolipoprotein E (APOE) is a key protein in vertebrates, sharing structural and functional traits with insect apolipophorin-III, suggesting evolutionary links.
• Human APOE exhibits unique functional polymorphism with three major alleles: ε4, ε3, and ε2, unlike other species.
• The APOE ε4 allele, though ancestral and linked to age-related disease, persists globally and is the second most common allele.

Purpose of the Study:

• To review current knowledge on APOE gene structure, phylogeny, protein topology, and human isoforms.
• To explore the evolutionary dynamics of human APOE isoforms and their geographical distribution.
• To investigate potential selective forces, including dietary factors, driving APOE evolution.

Main Methods:

• Literature review of existing research on APOE.
• Analysis of APOE gene structure and protein topology.
• Examination of APOE allele frequencies and geographical distribution.

Main Results:

• The ε4 allele is the ancestral form of APOE and is associated with increased age-related disease risk.
• APOE ε4 and ε2 alleles exhibit non-random geographical and ethnic distributions, suggesting evolutionary selection.
• Differential interactions with dietary factors, such as micronutrients and macronutrient composition, are implicated in APOE evolution.

Conclusions:

• Human APOE isoforms are shaped by evolutionary selective pressures, not solely by disease association.
• Dietary factors likely play a significant role in the evolution and distribution of APOE alleles.
• Understanding APOE evolution is crucial for comprehending human health and disease variations.