Linking ecological immunology and evolutionary medicine: the case for apolipoprotein E

Abstract

Summary1. Evolutionary medicine seeks to understand whether and to what extent aspects of human disease are adaptations for coping with infections or injuries, or the consequence of mismatches between modern and ancestral environments. Ecological immunology by comparison focuses largely on how organisms balance investments in immune defences against other traits (e.g., cognitive and reproductive functions) to maximize fitness. 2. Here we address the potential benefit of merging these two young disciplines by reviewing the biomedical literature involving variation at the human apolipoprotein epsilon (apoE) locus. Allelic variants at this locus are differentially susceptible to certain parasites [e.g. herpes-simplex virus-1 (HSV-1) and Chlamydia pneumoniae], as well as Alzheimer's and coronary artery disease, although susceptibility is impacted by environmental factors such as exercise and diet. ApoE variants also exhibit extensive physiological differences, particularly in immune and cognitive traits. 3. Considered altogether, we suggest that apoe-associated diseases are maladaptive plastic responses to conditions in modern environments, and predict that allelic variation at the apoE locus arose as both a consequence of genetic accommodation of historically adaptive environmental responses and because of the particular susceptibility of lipid transport molecules as infection pathways for certain parasites. 4. The goal of this paper is not to support unequivocally this hypothesis because relevant data remain scarce. We intend instead to provide a framework whereby existing hypotheses, which tend to emphasize faulty signalling via one allele (apoE4), can be evaluated through ecologicallyinformed experiments.

Do leprosy and tuberculosis generate a systemic inflammatory shift? Setting the ground for a new dialogue between experimental immunology and bioarchaeology

“…Therfore, we must consider that the immune system is characterized by a high degree of plasticity, and marked fluctuations can occur as a reaction to environmental factors (French et al, 2009). An emerging discipline such as human ecological immunology can help us to understand how ecological and social factors affect and reshape our immune system (McDade 2003(McDade , 2005McDade et al, 2010;Trotter et al, 2011).…”

An introduction to ecological immunology

“…The fourth and fifth papers attempt to provide applied value to ecoimmunology by illustrating insights provided by ecoimmunology to other research areas, namely Darwinian medicine (Nesse & Stearns 2008) and disease ecology (Raffel, Martin & Rohr 2008). Trotter et al (2011) use a case study approach to integrate ecoimmunology and Darwinian medicine, reviewing how human diseases associated with allelic variation at the apolipoprotein E locus might be a consequence of mismatched plastic phenotypic responses to modern environments. Hawley & Altizer (2011) suggest that unification of ecoimmunology and disease ecology will inform how within host processes translate to between host dynamics in terms of parasite transmission and persistence.…”

A tale of agriculturalists and hunter‐gatherers: Exploring the thrifty genotype hypothesis in native South Americans

“…We observed significantly higher frequencies for the thrifty allele in hunter‐gatherers (rs429358C, APOE ), but no significant differences in most of the other markers. Due to its vital role in various processes, the profound influences of APOE on human health and lifespan have been broadly studied (Joshi, Fischer, Schraut, Campbell, Esko, & Wilson, ; Napolioni, Giannì, Carpi, Predazzi, & Lucarini, ; Schupf et al, ; Trotter, Liebl, Weeber, & Martin, ). E2 carriers have lower plasma levels of total and LDL cholesterol than E3 carriers.…”

“…The E2, E3, and E4 haplotypes show varying distributions among human populations, with E3 being the most prevalent in many human groups (Singh, Singh,& Mastana, ). E4, the ancestral allele, is fixed in chimpanzees and other primates (Hanlon and Rubinsztein, ), whereas E3 is estimated to have appeared within the last 235,000 years (Trotter et al, ). Denisova is homozygous for the E3 haplotype, which implies that E3 was segregating in Homo populations 550‐765 kya before splitting of the archaic/African lineage (Denisova + Neanderthal/ H. sapiens ; Prüfer et al, ).…”