Revising Life’s Instructions?

Is DNA life’s recipe—or just a cupboard full of ingredients?

The standard view of heredity is that all information passed down from one generation to the next is stored in the genome. But Antony Jose, associate professor of cell biology and molecular genetics, argues in two new papers that the true story of the set of instructions used to build and maintain a living organism is much more complicated.

Jose presented his new theoretical framework for heredity—that these instructions are stored in the molecules that regulate a cell’s DNA and other functioning systems—in peer-reviewed papers published last week in the Journal of the Royal Society Interface and the journal BioEssays. 

Jose’s theory, developed through 20 years of research on genetics and epigenetics, suggests scientists may be overlooking important avenues for studying and treating hereditary diseases, and current beliefs about evolution may be overly focused on the role of the genome, which contains all of an organism’s DNA.

“DNA cannot be seen as the ‘blueprint’ for life,” Jose said. “It is at best an overlapping and potentially scrambled list of ingredients that is used differently by different cells at different times.”

For example, the gene for eye color exists in every cell of the body, but the process that produces the protein for eye color only occurs during a specific stage of development and only in the cells that constitute the colored portion of the eyes. That information is not stored in the DNA.

In addition, scientists are unable to determine the complex shape of an organ such as an eye, or that a creature will have eyes at all, by reading its DNA. These fundamental aspects of anatomy are dictated by something else.

Jose argues that these aspects of development, which enable a fertilized egg to grow from a single cell into a complex organism, must be seen as an integral part of heredity. Jose’s new framework recasts heredity as a complex, networked information system in which all the regulatory molecules that help the cell to function can constitute a store of hereditary information.

Jose’s approach could help answer many questions not addressed by the current genome-centric view of biology, said Michael Levin, a professor of biology and director of the Tufts Center for Regenerative and Developmental Biology and the Allen Discovery Center at Tufts University

“Understanding the transmission, storage and encoding of biological information is a critical goal, not only for basic science but also for transformative advances in regenerative medicine,” said Levin, who was not involved with either published paper. “Antony Jose masterfully applies a computer science approach to provide an overview and a quantitative analysis of possible molecular dynamics that could serve as a medium for heritable information.”

Jose proposes that instructions not coded in the DNA are contained in the arrangement of the molecules within cells and their interactions with one another. This arrangement of molecules is preserved and passed down from one generation to the next.

In his papers, Jose’s framework recasts inheritance as the combined effects of three components: entities, sensors and properties, that together enable a living organism to sense or “know” things about itself and its environment. Some of this knowledge is used along with the genome in every generation to build an organism.

The folly of maintaining a genome-centric view of heredity, according to Jose, is that scientists may be missing opportunities to combat heritable diseases and to understand the secrets of evolution. In medicine, for instance, research into why hereditary diseases affect individuals differently focuses on genetic differences and on chemical or physical differences in entities.

But this new framework suggests researchers should be looking for non-genetic differences in the cells of individuals with hereditary diseases, such as the arrangement of molecules and their interactions. Scientists don’t currently have methods to measure some of these things, so this work points to potentially important new avenues for research.

“Given how two people who contract the same disease do not necessarily show the same symptoms, we really need to understand all the places where two people can be different—not just their genomes,” Jose said.