It is generally accepted that humans and almost all other organisms pass heredity from parent to offspring through the information stored in its DNA. Antony Jose, associate professor of cell biology and molecular genetics at the University of Maryland, outlined a new theoretical framework for heredity, which was developed through 20 years of research on genetics and epigenetics.
In two peer-reviewed papers, recently published in the Journal of the Royal Society Interface and the journal BioEssays, Jose proposes that DNA is just the ingredient list, not the set of instructions used to build and maintain a living organism. The instructions, he says, are much more complicated, and they're stored in the molecules that regulate a cell's DNA and other functioning systems.
"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 colour only occurs during a specific stage of development and only in the cells that constitute the coloured portion of the eyes. That information is not stored in the DNA.
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.
Jose's argument suggests that 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.
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 the creature's DNA. These fundamental aspects of anatomy are dictated by something outside of the DNA.
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.
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, believes Jose's approach could help answer many questions not addressed by the current genome-centric view of biology. Levin was not involved with either of the published papers.
In his papers, Jose's framework recasts inheritance as the combined effects of three components: entities, sensors and properties.
Entities include the genome and all the other molecules within a cell that are needed to build an organism. Entities can change over time, but they are recreated with their original structure, arrangement and interactions at the start of each generation.
"That aspect of heredity, that the arrangement of molecules is similar across generations, is deeply underappreciated, and it leads to all sorts of misunderstandings of how heredity works," Jose said.
Sensors are specific entities that interact with and respond to other entities or to their environment. Sensors respond to certain properties, such as the arrangement of a molecule, its concentration in the cell or its proximity to another molecule.
Together, entities, sensors and properties 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 evolution, Jose's framework suggests that organisms could evolve through changes in the arrangement of molecules without changes in their DNA sequence. And in conservation science, this work suggests that attempts to preserve endangered species through DNA banks alone are missing critical information stored in non-DNA molecules.
"Antony Jose's generalisation of memory and encoding via the entity-sensor-property framework sheds novel insights into evolution and biological complexity and suggests important revisions to existing paradigms in genetics, epigenetics and development," Levin said.
