Evolutionary and Developmental Mismatch: Evolutionary and Epigenetic Perspectives on Non-Communicable Disease
Evolutionary Medicine Month at UCLA 2014 Sir Peter Gluckman, FRS, University
Sir Peter Gluckman, FRS, University Distinguished Professor of Pediatrics and Perinatal Biology, Centre for Human Evolution, Adaptation, and Disease, Liggins Institute
University of Auckland and Singapore Institute for Clinical Sciences
Evolutionary principles in medicine are primarily of use in developing conceptual models of ultimate pathways to causation and generating hypotheses as to proximate mechanisms that can be tested. The developmental origins paradigm provides a good example of the application of evolutionary principles to dissect out complex phenomena. There is considerable evidence showing that the fetus is affected by the maternal environment and attention in recent decades has focused on the longer-term metabolic consequences and the implications for non-communicable disease (NCD). However confusion as to the nature of these relationships, the delay in recognizing there are multiple pathways, possible mechanisms and the lack of a plausible conceptual framework has delayed the incorporation of this knowledge into public health. I will present empirical data to address these issues and illustrate evolutionary medical concepts.
It is important to distinguish severe intrauterine exposures with teratogenic consequences from those occurring within the normative range of exposures (eg nutrition, stress, maternal mood) and normative variations (eg parity,) from those that reflect evolutionarily novel environments (for example maternal obesity, gestational diabetes, formula feeding). There is now good clinical evidence supported by mechanistic (epigenetic) observations to show that developmental trajectories can be affected by normative exposures. These processes of normative developmental plasticity are evolutionarily conserved and are termed predictive adaptive responses (PARs) because of their potentially adaptive advantages. This somewhat contested conceptual framework has been experimentally validated and there is supportive clinical evidence from studies of kwashiorkor and marasmus. However in the mismatch of modern postnatal environments, these mechanisms can manifest later in life as an increased risk of disease. Critiques of this framework largely arose from misunderstandings of the concept of maternal-fetal conflict and of the importance of different life history strategies across species. Less is known about the potential for paternal influences via epigenetic mechanisms. A deeper issue is how important are these developmental pathways to the modern context of the NCD epidemic. Epigenetic analyses suggest that developmental pathways play a far more important role than is generally considered and certainly greater than that of fixed genomic variation. However there are significant technical issues in epigenetic epidemiology that arise in part from the nature of the data and in part because of the need to consider genotypic-epigenotypic interactions. A consideration of the latter points to a broader range of developmental considerations than has been generally appreciated from animal studies. Nevertheless such data also point to the potential to use epigenetic biomarkers to optimize the early developmental environment and to reduce the risk of NCDs significantly by greater attention to primary prevention in early life.
(Wednesday) 8:30 am - 9:30 pm
Tamkin Auditorium, Ronald Reagan UCLA Medical Center