Diametrical diseases reflect evolutionary-genetic tradeoffs

Abstract

Tradeoffs centrally mediate the expression of human adaptations. We propose that tradeoffs also influence the prevalence and forms of human maladaptation manifest in disease. By this logic, increased risk for one set of diseases commonly engenders decreased risk for another, diametric, set of diseases. We describe evidence for such diametric sets of diseases from epidemiological, genetic and molecular studies in four clinical domains: (i) psychiatry (autism vs psychotic-affective conditions), (ii) rheumatology (osteoarthritis vs osteoporosis), (iii) oncology and neurology (cancer vs neurodegenerative disorders) and (iv) immunology (autoimmunity vs infectious disease). Diametric disorders are important to recognize because genotypes or environmental factors that increase risk for one set of disorders protect from opposite disorders, thereby providing novel and direct insights into disease causes, prevention and therapy. Ascertaining the mechanisms that underlie disease-related tradeoffs should also indicate means of circumventing or alleviating them, and thus reducing the incidence and impacts of human disease in a more general way.

The elephant in the room: What matters cognitively in cumulative technological culture

“…Probably not, because technical expertise usually comes with costs in social skills that would stymie social transmission. Indeed, "folk physics" shows clear evidence of tradeoffs with "folk psychology" (Baron-Cohen 2000; Baron-Cohen et al 2001), technical and visual-spatial skills trade off with social abilities more generally in autistic as well as non-autistic individuals (Crespi & Go 2015 , Table 1), and autism is well known to engender reductions in ability and/or motivation to imitate, emulate, innovate, engage in joint attention, and, most broadly, enculturate (e.g., Baron-Cohen 1993;Charman 2003;Colombi et al 2009). The existence of such tradeoffs vitiates the direct connection of technical reasoning with imitation and innovation posited by O&R as key to their model.…”

Impact of demography and population dynamics on the genetic architecture of human longevity

“…Interestingly, tradeoffs occur when a trait cannot increase without a decrease in another one and it has been supposed that beneficial genotypes may pleiotropically generate deleterious effects in phenotypes that trade off with them. This concept has been proposed for many diseases, such as cancer, neurodegeneration, autoimmune and infectious diseases [ 9 ]. It has been also suggested that an evolutionary approach that relies on models/assumptions of population genetics may help in predicting the genetic background of susceptibility to such diseases [ 6 , 10 – 12 ].…”

The HLA 8.1 ancestral haplotype in schizophrenia: dual implication in neuro‐synaptic pruning and autoimmunity?

“…The latter may explain the reported association of 8.1 AH with protection against infectious events . By conferring susceptibility to autoimmune disorders on one hand and protection against infections on the other, the 8.1 AH can be considered as a prototypic example of evolutionary‐genetic trade‐offs in conferring diametric disease risks further influenced by genetic and environmental variations . Under the diametric model, the postulation is that the Initial pathogen‐driven pressure positively selects the 8.1 AH, which over time, when the pressure load diminishes, as of today, expresses its deleterious effect in terms of autoimmunity.…”