Genotype-to-phenotype mapping commonly focuses on two major classes of mutations: single nucleotide polymorphisms (SNPs) and copy number variation (CNV). Here, we discuss an underestimated third class of genotypic variation: changes in microsatellite and minisatellite repeats. Such tandem repeats (TRs) are ubiquitous, unstable genomic elements that have historically been designated as nonfunctional "junk DNA" and are therefore mostly ignored in comparative genomics. However, as many as 10% to 20% of eukaryotic genes and promoters contain an unstable repeat tract. Mutations in these repeats often have fascinating phenotypic consequences. For example, changes in unstable repeats located in or near human genes can lead to neurodegenerative diseases such as Huntington disease. Apart from their role in disease, variable repeats also confer useful phenotypic variability, including cell surface variability, plasticity in skeletal morphology, and tuning of the circadian rhythm. As such, TRs combine characteristics of genetic and epigenetic changes that may facilitate organismal evolvability.

Ten years ago, the discovery of Mimivirus, a virus infecting Acanthamoeba, initiated a reappraisal of the upper limits of the viral world, both in terms of particle size (>0.7 micrometers) and genome complexity (>1000 genes), dimensions typical of parasitic bacteria. The diversity of these giant viruses (the Megaviridae) was assessed by sampling a variety of aquatic environments and their associated sediments worldwide. We report the isolation of two giant viruses, one off the coast of central Chile, the other from a freshwater pond near Melbourne (Australia), without morphological or genomic resemblance to any previously defined virus families. Their micrometer-sized ovoid particles contain DNA genomes of at least 2.5 and 1.9 megabases, respectively. These viruses are the first members of the proposed "Pandoravirus" genus, a term reflecting their lack of similarity with previously described microorganisms and the surprises expected from their future study.

Significance Giant DNA viruses are visible under a light microscope and their genomes encode more proteins than some bacteria or intracellular parasitic eukaryotes. There are two very distinct types and infect unicellular protists such as Acanthamoeba . On one hand, Megaviridae possess large pseudoicosahedral capsids enclosing a megabase-sized adenine–thymine-rich genome, and on the other, the recently discovered Pandoraviruses exhibit micron-sized amphora-shaped particles and guanine–cytosine-rich genomes of up to 2.8 Mb. While initiating a survey of the Siberian permafrost, we isolated a third type of giant virus combining the Pandoravirus morphology with a gene content more similar to that of icosahedral DNA viruses. This suggests that pandoravirus-like particles may correspond to an unexplored diversity of unconventional DNA virus families.