An alternative approach to medical genetics based on modern evolutionary biology. Part 1: mutation and symbiogenesis.

Abstract

The need to understand the genetic underpinning of common diseases, such as cancer, diabetes and autoimmune disorders, is a major challenge facing medical genetics. While many disorders involve a complex interaction between genetic traits and environmental influences, a significant proportion involve specific genetic causes that are diagnosable and thus amenable to therapeutic approaches, including family counselling, specific lines of chemically-directed therapy and even the possibility of addressing the underlying genetic causation through specific genetic therapy. The genetic approach to medicine has always found commonalities with the disciplines of evolutionary biology: only when we understand the evolutionary origins of the human genome can we aspire to understand how ‘normality’, in terms of genetics and epigenetics, becomes subverted in disease. Since the 1930s, mutation has been assumed to be the exclusive explanation of the hereditary basis of disease. But advances in evolutionary biology over the last two decades have introduced three additional, and important, sources of hereditary variation, namely symbiogenesis, particularly symbiogenesis involving viruses, epigenetics and hybridogenesis, all of which are now seen to have played important roles in the evolution of biodiversity. These additional mechanisms have played a major role in the evolution of the human genome – indeed they help to explain what would otherwise appear to be some paradoxical aspects of its construction and make-up. In this paper, and the four linked papers that follow it, I shall explain the evolutionary advances and show how, together with the knowledge already accrued from the study of mutation, they provide a more comprehensive understanding of the hereditary basis of human disease.