As the previous chapter indicated, a gene is much more, and more subtle, than simply a linear coding sequence. That sequence works only in the context of surrounding regulatory sequences and in the presence of the appropriate regulatory environment in the nucleus. Until recently, our knowledge of genetics was too rudimentary to enable us to make much headway in understanding how complex phenotypes result from genotypes. Darwin considered the problem essentially insoluble.

Phenotypes are also more complicated than can be explained simply by the linear coding sequence of a gene. Proteins have secondary and tertiary structures upon which their physiological functions depend. Even single proteins are only partial phenotypes, because their concentrations, induction, and tissue-specific environments and expression are also relevant to their action. Variation in regulatory and many other genes affects how the protein will function, just as variation in the sequence of the protein itself does.

An understanding of the relationships between genes and phenotypes requires an understanding of the logic by which life operates and has evolved. This is important because mutations can interrupt function at any point, and the pattern of pathology of a given genetic disease is often a direct reflection of where in the system the disruption occurs.