Adult disease: echoes of the past

Abstract

Disease occurs if an environmental challenge exceeds the ability of an individual to mount an effective adaptive response to it. Evolution has selected genomically determined traits, which are optimal for a species to survive the historical environment. However, this adaptive ability to withstand an environmental challenge varies among individuals and is itself a phenotypic characteristic: how is this determined? We argue that maternal and placental cues that constrain prenatal development, induce offspring to develop predictive adaptive responses more suited to a deprived postnatal environment, i.e. a more favorable phenotype for survival of the species than that which would be established by the genotype in the absence of environmental influence. This ‘survival phenotype’ can be exaggerated further by the postnatal environment. Since predictive adaptive responses maximize the chance of survival to reproduce, this phenomenon has itself been protected through evolution. Furthermore, such rapid adaptive responses may allow transgenerational transmission of phenotypic traits advantageous for survival of a species through transient environmental change. We argue that risk of disease is increased, when the actual postnatal environment does not match that predicted prenatally. In humans, this explains patterns of disease, especially those for which risk is determined in part during development, such as type 2 diabetes, cardiovascular disease and the rising risks of childhood obesity. The predictive adaptive response hypothesis extends foregoing concepts in this field and lends itself to experimental testing. It provides insights into ways to reduce the burden of certain common chronic diseases in both developed and developing countries.