The low mutation rate of DNA systems allows the use of techniques including single-nucleotide polymorphism (SNP) and deletion/insertion polymorphism (DIP) assays in forensic analysis.3-13 In addition, a modification of these assays based on melting temperature profiles of the DNA segments that compose the total DNA sample offers a less expensive genotyping method.14 Multiplex DNA amplification can be optimized and used to produce up to 30 simultaneous DNA targets, mostly consisting of fragments containing SNPs that can be differentiated by size, and used for diagnostic and forensic pur-poses.15 Higher mutability and rapid evolutionary capabilities of RNA viral genomes require that other approaches be taken.
Many important viral pathogens have an RNA genome. RNA viral pathogens are abundant in humans, animals, and plants.16 Over the last decade, work with many RNA viruses has established that they all share high mutability and rapid evolutionary capabilities. Their genetic plasticity may in part explain why they are frequently "emerging pathogens" in new hosts.17-24
Due to lack of proofreading of the RNA polymerases and to the high error rate of reverse transcriptases,25-27 RNA viruses exhibit high mutation rates that result in genetically heterogeneous populations in continuous competition: these are able to select the best-adapted variants for each particular environment in a quasi-deterministic fashion.28-32 Features of RNA replication are high mutation rates, short replication times, and high progeny yields. These lead to misincorporation of at least 1 nucleotide every 1,000 to 100,000 nucleotides. Mutation rates per nucleotide site in the range of 10-3 to 10-5 for a 10-kb genome ensure that each progeny genome includes on average 0.1-10 muta-tions.30,32-37 As a result, RNA virus populations are composed of a wide variety of individuals, rarely identical to each other but highly similar genetically, in which most individuals conserve the better fitness-adapted genetic information (master sequence).30,32,38-41 The advantage of this population structure (quasispecies) is that the species may overcome almost any change in the environment with just a switch in the master sequence, giving replicative advantage under new conditions to the most-fit individual among minor variants.42 The quasispecies concept was proposed by Eigen et al. to describe error-prone replication and self-organization of primitive macromolecules.40,41,43,44 The concept has proven useful for explaining and understanding RNA genetic elements which are subjected to a continuous dynamic of mutation, competition, and selection.45-50 Application of the quasispecies concept of population distribution and evolution to RNA viruses has also been very useful for developing an understanding of their biology in nature.
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