International audienceIn contrast with former definitions of life limited to membrane-bound cellular life forms which feed, grow, metabolise and replicate (i) a role of viruses as genetic symbionts, (ii) along with peripheral phenomena such as cryptobiosis and (iii) the horizontal nature of genetic information acquisition and processing broaden our view of the tree of life. Some researchers insist on the traditional textbook conviction of what is part of the community of life. In a recent review they assemble four main arguments which should exclude viruses from the tree of life because of their inability to self-sustain and self-replicate, their polyphyly, the cellular origin of their cell-like genes and the volatility of their genomes. In this article we will show that these features are not coherent with current knowledge about viruses but that viral agents play key roles within the roots and stem of the tree of life

Recent investigations surprisingly indicate that single RNA "stem-loops" operate solely by chemical laws that act without selective forces, and in contrast, self-ligated consortia of RNA stem-loops operate by biological selection. To understand consortial RNA selection, the concept of single quasi-species and its mutant spectra as drivers of RNA variation and evolution is rethought here. Instead, we evaluate the current RNA world scenario in which consortia of cooperating RNA stem-loops (not individuals) are the basic players. We thus redefine quasispecies as RNA quasispecies consortia (qs-c) and argue that it has essential behavioral motifs that are relevant to the inherent variation, evolution and diversity in biology. We propose that qs-c is an especially innovative force. We apply qs-c thinking to RNA stem-loops and evaluate how it yields altered bulges and loops in the stem-loop regions, not as errors, but as a natural capability to generate diversity. This basic competence-not error-opens a variety of combinatorial possibilities which may alter and create new biological interactions, identities and newly emerged self identity (immunity) functions. Thus RNA stem-loops typically operate as cooperative modules, like members of social groups. From such qs-c of stem-loop groups we can trace a variety of RNA secondary structures such as ribozymes, viroids, viruses, mobile genetic elements as abundant infection derived agents that provide the stem-loop societies of small and long non-coding RNAs.

Whereas telomeres protect terminal ends of linear chromosomes, telomerases identify natural chromosome ends, which differ from broken DNA and replicate telomeres. Although telomeres play a crucial role in the linear chromosome organization of eukaryotic cells, their molecular syntax most probably descended from an ancient retroviral competence. This indicates an early retroviral colonization of large double-stranded DNA viruses, which are putative ancestors of the eukaryotic nucleus. This contribution demonstrates an advantage of the biosemiotic approach towards our evolutionary understanding of telomeres, telomerases, other reverse transcriptases and mobile elements. Their role in genetic/ genomic content organization and maintenance is no longer viewed as an object of randomly derived alterations (mutations) but as a highly sophisticated hierarchy of regulatory networks organized and coordinated by natural genome-editing competences of viruses.

The biocommunicative approach investigates communication processes within and among cells, tissues, organs and organisms as sign-mediated interactions, and nucleotide sequences as code, i.e. language-like text, which follows in parallel three kinds of rules: combinatorial (syntactic), context-sensitive (pragmatic), and content-specific (semantic). Natural genome editing from a biocommunicative perspective is competent agent-driven generation and integration of meaningful nucleotide sequences into pre-existing genomic content arrangements and the ability to (re-)combine and (re-)regulate them according to context-dependent (i.e. adaptational) purposes of the host organism.

In the early 1970s, Manfred Eigen and colleagues developed the quasispecies model (qs) for the population-based origin of RNAs representing the early genetic code. The Eigen idea is basically that a halo of mutants is generated by error-prone replication around the master fittest type which will behave similarly as a biological population. But almost from the start, very interesting and unexpected observations were made regarding competition versus co-operation which suggested more complex interactions. It thus became increasingly clear that although viruses functioned similar to biological species, their behavior was much more complex than the original theory could explain, especially adaptation without changing the consensus involving minority populations. With respect to the origin of natural codes, meaning, and code-use in interactions (communication), it also became clear that individual fittest type-based mechanisms were likewise unable to explain the origin of natural codes such as the genetic code with their context-and consortia-dependence (pragmatic nature). This, instead, required the participation of groups of agents competent in the code and able to edit code because natural codes do not code themselves. Three lines of inquiry, experimental virology, quasispecies theory, and the study of natural codes converged to indicate that consortia of cooperative RNA agents such as viruses must be involved in the fitness of RNA and its involvement in communication, i.e., code-competent interactions. We called this co-operative form quasispecies consortia (qs-c). They are the essential agents that constitute the possibility of evolution of biological group identity. Finally, the basic interactional motifs for the emergence of group identity, communication, and cooperation-together with its opposing functions-are explained by the ''Gangen'' hypothesis.

The DNA serves as a stable information storage medium and every protein which is needed by the cell is produced from this blueprint via an RNA intermediate code. More recently it was found that an abundance of various RNA elements cooperate in a variety of steps and substeps as regulatory and catalytic units with multiple competencies to act on RNA transcripts. Natural genome editing on one side is the competent agent-driven generation and integration of meaningful DNA nucleotide sequences into pre-existing genomic content arrangements, and the ability to (re-)combine and (re-)regulate them according to context-dependent (i.e. adaptational) purposes of the host organism. Natural genome editing on the other side designates the integration of all RNA activities acting on RNA transcripts without altering DNA-encoded genes. If we take the genetic code seriously as a natural code, there must be agents that are competent to act on this code because no natural code codes itself as no natural language speaks itself. As code editing agents, viral and subviral agents have been suggested because there are several indicators that demonstrate viruses competent in both RNA and DNA natural genome editing.

Most molecular biological concepts derive from physical chemical assumptions about the genetic code that are basically more than 40 years old. Additionally, systems biology, another quantitative approach, investigates the sum of interrelations to obtain a more holistic picture of nucleotide sequence order. Recent empirical data on genetic code compositions and rearrangements by mobile genetic elements and noncoding RNAs, together with results of virus research and their role in evolution, does not really fit into these concepts and compel a reexamination. In this review, we try to find an alternate hypothesis. It seems plausible now that if we look at the abundance of regulatory RNAs and persistent viruses in host genomes, we will find more and more evidence that the key players that edit the genetic codes of host genomes are consortia of RNA agents and viruses that drive evolutionary novelty and regulation of cellular processes in all steps of development. This agent-based approach may lead to a qualitative RNA sociology that investigates and identifies relevant behavioral motifs of cooperative RNA consortia. In addition to molecular biological perspectives, this may lead to a better understanding of genetic code evolution and dynamics.

a b s t r a c tThe concepts of the origin of the genetic code and the definitions of life changed dramatically after the RNA world hypothesis. Main narratives in molecular biology and genetics such as the "central dogma," "one gene one protein" and "non-coding DNA is junk" were falsified meanwhile. RNA moved from the transition intermediate molecule into centre stage. Additionally the abundance of empirical data concerning nonrandom genetic change operators such as the variety of mobile genetic elements, persistent viruses and defectives do not fit with the dominant narrative of error replication events (mutations) as being the main driving forces creating genetic novelty and diversity. The reductionistic and mechanistic views on physico-chemical properties of the genetic code are no longer convincing as appropriate descriptions of the abundance of non-random genetic content operators which are active in natural genetic engineering and natural genome editing.