Genetics as Explanation: Limits to the Human Genome Project

Abstract

Abstract Living organisms are composed of cells and all living cells contain a genome, the organism's stock of deoxyribonucleic acid (DNA). The role of the genome has been likened to a computer program that encodes the organism's development and its subsequent response to the environment. Thus, the organism and its fate can be explained by genetics, the plans written into the sequence of genomic DNA; the Human Genome Project was devised to decipher this program. However, it is now clear that the genome does not directly program the organism; the computer program metaphor has misled us. The genome is only one class of vital information that serves the organism. Indeed, we now know that the healthy individual human is an ecosystem that lives in symbiosis with hundreds of different species of bacteria – the microbiota. Metaphorically, the genome can be likened to a toolbox for accomplishing specific tasks. Key Concepts The genome does not function as a master plan or computer program for controlling the organism; the genome is the organism's servant, not its master. The genome is a reservoir of DNA sequence information and a vehicle for transmitting this information; the meaning of DNA emerges from the cellular processing of this raw information into proteins and other functional molecules. Complex organisms like humans live in symbiosis with a microbiota of many hundreds of micro‐organisms. The microbiota are essential to human health and the phenotype of the individual is greatly influenced by interactions with the microbiota. The body houses manyfold more DNA of microbial origin than it does the genomic DNA inherited from the parents. The individual is thus an ecosystem of diverse cellular origins. DNA is only one class of vital information that serves the organism; the organism epigenetically uses, manipulates, regulates and, in the case of the immune system, creates genes. The effects of a gene vary with the organism's environment; the interactions between genes and environment are not linear and, in most cases, not additive. Therefore, one cannot compute with certainty the relative contributions of genes and environment to an organism's observed features – its phenotype. Metaphorically, we can think of the genome as akin to a list of words, a vocabulary, which can be used to build and express a meaningful language; like a vocabulary, a genome by itself has no functional meaning. The genome is thus akin to a toolbox of DNA sequences that provide molecular tools as requested by the internal state of the organism and the state of the environment. One's genes cannot explain one's being: an organism is the expression of a dynamic and ongoing interaction between the state of its environment and its internal state, which includes its past history and its toolbox of DNA sequences.

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