The hypergenome in inheritance and development

Abstract

Both theory and experimentation suggest that during development, the DNA of multicellular organisms, recognized as graced with a lifelong intrinsic stability, is instead target of several modifications (point mutations, larger structural variations, epigenetic marks) and partner of complex interactions with non-DNA moieties (RNAs and proteins). Some of these modifications probably affect a fraction of the genome larger than standard point mutations and are more likely to respond to environmental cues. Thus, the traditional concepts of gene and genome need revision: the structure serving as depository of the overall bioinformation of the cell is more dynamic and less homogeneous than allowed for by the Central Dogma, since in addition to DNA, it includes also RNA and proteins. Each of the individual contributors as well as their stoichiometry undergo modifications. Compared to the traditional unidimensional and static genome, the resulting dynamic aggregate could be more competent to cope with different regulatory requirements: its structural variations may respond to unscheduled macro- and microenvironmental stresses as well as to scheduled genetic programs. A detailed assessment of these variations in time and space should provide a basis for a deeper comprehension of the phenotypic changes punctuating the organism's physio-pathological development, aging and transgenerational transmission. The variations of such information storage-delivery system may interest also the germ cells: the inheritance of parental traits and hence their evolutionary transmission would be affected. For the structure featuring all these properties, we propose the term 'hypergenome' to underscore the dynamic composition of a complex nucleoprotein responsive to both unpredictable environmental stimuli and internal built-in programs.