Mechanisms of viral emergence

Domingo, Esteban

The mechanisms of genetic variation of viruses are blind forces (mutation, recombination and gene transfer events) that have acted historically to build the biosphere we know, under the guidance of natural selection. Eigen and Biebricher adapted the concept of sequence space, originally formulated by Maynard Smith for proteins [50] , to describe all the possible nucleotide sequences that a given replicating entity can have [19] . The theoretical sequence space of any organism or any virus is huge (4 n ), being n the number of genomic nucleotides. Only a minute portion of the theoretical sequence space is compatible with virus infectivity and survival. Mutation prompts exploration of neighbor sites in sequence space, while recombination offers the possibility to explore distant sites in sequence space. Nonhomologous recombination events (that is, those that occur between genomes or genomic sites that do not show nucleotide sequence identity) constitute a means to promote exchanges of genetic material among organisms that belong to distant phyla, including exchanges between viruses and cells. Recent developments in genomics are unveiling surprising relationships among very distant organisms, giving rise to a tree of life with inter-kingdom connections due to lateral gene transfers, that were unsuspected just a few decades ago [7] .