The theory of evolution was first proposed based on visual observations of animals and plants. Then, in the latter half of the 19th century, the invention of the modern optical microscope helped scientists begin to systematically explore the vast world of previously invisible organisms, dubbed “microbes” by the late, great Louis Pasteur, and led to a rethinking of the classification of living things.
In the mid-1970s, based on the analysis of the ribosomal genes of these organisms, Carl Woese and others proposed a classification that divided living organisms into three domains: eukaryotes, bacteria, and archaea. (See “Discovering Archaea, 1977,” The Scientist, March 2014)
Even though viruses were by that time visible using electron microscopes, they were left off the tree of life because they did not possess the ribosomal genes typically used in phylogenetic analyses. And viruses are still largely considered to be nonliving biomolecules—a characterization spurred, in part, by the work of 1946 Nobel laureate Wendell Meredith Stanley, who in 1935 succeeded in crystallizing the tobacco mosaic virus.
Even after crystallization, the virus maintained its biological properties, such as its ability to infect cells, suggesting to Stanley that the virus could not be truly alive.
Recently, however, the discovery of numerous giant virus species—with dimensions and genome sizes that rival those of many microbes—has challenged these views. (See illustration.) In 2003, my colleagues and I announced the discovery of Mimivirus, a parasite of amoebae that researchers had for years considered a bacterium. With a diameter of 0.4 micrometers (μm) and a 1.2-megabase-pair DNA genome, the virus defied the predominant notion that viruses could never exceed 0.2 μm.
Since then, a number of other startlingly large viruses have been discovered, most recently two Pandoraviruses in July 2013, also inside amoebas. Those viruses harbor genomes of 1.9 million and 2.5 million bases, and for more than 15 years had been considered parasitic eukaryotes that infected amoebas.
Now, with the advent of whole-genome sequencing, researchers are beginning to realize that most organisms are in fact chimeras containing genes from many different sources—eukaryotic, prokaryotic, and viral alike—leading us to rethink evolution, especially the extent of gene flow between the visible and microscopic worlds.
Genomic analysis has, for example, suggested that eukaryotes are the result of ancient interactions between bacteria and archaea. In this context, viruses are becoming more widely recognized as shuttles of genetic material, with metagenomic studies suggesting that the billions of viruses on Earth harbor more genetic information than the rest of the living world combined. (See “Going Viral,” The Scientist, September 2013.) These studies point to viruses being at least as critical in the evolution of life as all the other organisms on Earth.
A giant discovery
Despite the fact that viruses use the same genetic code as verifiably living things, science long classified them as mere collections of biomolecules. And because scientists assumed that viruses had both an upper size limit of just 0.2 μm and a parasitic nature, they classified them in a not-quite-biological world of their own.
That thinking started to change in the early 2000s, when my colleagues and I identified an unknown virus living inside an amoeba. It was as big as some bacteria and archaea and was visible under an optical microscope—qualifying it as a microbe under Pasteur’s original definition.
I named it Mimivirus as a personal joke about the stories that my father, a biomedical scientist, told me when I was a child to explain evolution; the stories were based on the life of “Mimi the amoeba.” I initially disguised the true source of this name, however, pretending that Mimivirus came from “MiMicking microbe.”
Resarchers had first noticed Mimivirus in 1992, but based on its appearance under light microscopy it had been considered an intracellular bacterium for several years. Transmission electron microscopy images depicting its ultrastructure, along with the determination of its genome sequence in 2004,3 however, confirmed that it was, in fact, part of the viral world. Mimivirus has no ribosomal genes, but its genome contains more than 1,200 genes—three times more than any virus known at the time. Its genome is larger than that of many bacteria and archaea and comparable to some eukaryotic genomes. Mimivirus was no ordinary virus.
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