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.

Hypothesis, analysis and synthesis, it's all Greek to me

“…Epigenome (Murrell et al, 2005) is an excellent example of a scientific term in which a Greek preposition ('epi'-, meaning 'on top of') is combined with the suffix -genome to make a word that is precise and logically consistent. Other (less well known) examples include antigenome (which is used in immunology; Sette et al, 2016), metagenome (Streit and Schmitz, 2004), progenome (Ferreira et al, 2004), and hypergenome (Sgaramella, 2013). We then went on to create new words of this kind (Table 2) that, we feel, remain true to their etymological roots while, at the same time, being potentially useful to the scientific community.…”

Understanding aneuploidy in cancer through the lens of system inheritance, fuzzy inheritance and emergence of new genome systems

“…Altogether, the complexity of aneuploidy makes studying its relationship with cancer extremely challenging (Table 1 ). Some known complications include: a) most cancer cases display non-clonal aneuploidy (impeding the fact that clonal aneuploidy has been much more commonly researched for decades) [ 5 – 9 ], b) aneuploidy often occurs in combination with other types of genetic/epigenetic and genomic aberrations (translocations and polyploidy) (Table 2 ) c) there is often a variable degree of somatic mosaicism [ 10 – 13 ], and d) there is a complex, dynamic relationship between aneuploidy and genome instability (Table 3 ). Interestingly, many common and complex diseases have been linked to non-clonal aneuploidy and somatic mosaicism as well [ 14 , 15 ], which has led to efforts to search for commonly shared mechanisms among different diseases or illness conditions [ 16 – 19 ].…”