The Evolving Definition of the Term Gene

This paper presents a history of the changing meanings of the term gene, over more than a century, and a discussion of why this word, so crucial to genetics, needs redefinition today. In this account, the first two phases of 20th century genetics are designated the classical and the neoclassical periods, and the current molecular-genetic era the modern period. While the first two stages generated increasing clarity about the nature of the gene, the present period features complexity and confusion. Initially, the term gene was coined to denote an abstract unit of inheritance, to which no specific material attributes were assigned. As the classical and neoclassical periods unfolded, the term became more concrete, first as a dimensionless point on a chromosome, then as a linear segment within a chromosome, and finally as a linear segment in the DNA molecule that encodes a polypeptide chain. This last definition, from the early 1960s, remains the one employed today, but developments since the 1970s have undermined its generality. Indeed, they raise questions about both the utility of the concept of a basic unit of inheritance and the long implicit belief that genes are autonomous agents. Here, we review findings that have made the classic molecular definition obsolete and propose a new one based on contemporary knowledge.