Genes without prominence: a reappraisal of the foundations of biology.

The sequencing of the human genome raises two intriguing questions: why has the prediction of the inheritance of common diseases from the presence of abnormal alleles proved so unrewarding in most cases and how can some 25 000 genes generate such a rich complexity evident in the human phenotype? It is proposed that light can be shed on these questions by viewing evolution and organisms as natural processes contingent on the second law of thermodynamics, equivalent to the principle of least action in its original form. Consequently, natural selection acts on variation in any mechanism that consumes energy from the environment rather than on genetic variation. According to this tenet cellular phenotype, represented by a minimum free energy attractor state comprising active gene products, has a causal role in giving rise, by a self-similar process of cell-to-cell interaction, to morphology and functionality in organisms, which, in turn, by a self-similar process entailing Darwin's proportional numbers are influencing their ecosystems. Thus, genes are merely a means of specifying polypeptides: those that serve free energy consumption in a given surroundings contribute to cellular phenotype as determined by the phenotype. In such natural processes, everything depends on everything else, and phenotypes are emergent properties of their systems.