Mendel's laws of heredity on his 200th birthday: What have we learned by considering exceptions?

Discovery in science is often driven forward more by exceptions than by rules. In the field of genetics, the basic ‘rules’ are often taught in the form of Mendel’s laws of heredity (Bateson 1909). Formally, these laws are given as the ‘law of dominance’, the ‘law of segregation’, and the ‘law of independent assortment’, which are all ultimately components of an underlying assumption of particulate diploid inheritance. We now recognise that these laws are manifestations of the formation of gametes through meiosis and inheritance of allelic variants at autosomal loci. Although these laws were developed in the absence of any understanding of their causal basis, they nonetheless hold (at least loosely speaking) quite broadly. Consequently, they provided a key foundation for the development of the field of genetics for much of the 20th century. However, recent decades have seen an explosion in discoveries that violate even the broad rules of quasi-Mendelian inheritance, which has driven the field of genetics forward by leaps and bounds. The more we learn, the more we realise that these ‘exceptions’ can play key roles in shaping patterns of inheritance and can have important impacts on evolutionary processes. Hence, while the cliché may be that the exceptions prove the rule, when it comes to inheritance, it is becoming obvious that the exceptions complement the rule, and that, together, the rules and their exceptions combine to form a unified framework for understanding the basis of variation in nature.