and animals. It’s possible that every cellular form of life on the planet supports at least one RNA virus, he had said in the book, though we don’t know for sure because we’ve just begun looking. A glance at his virosphere poster, which portrayed the universe of known viruses as a brightly colored pizza, was enough to support that point. It showed RNA viruses accounting for at least half the slices. But they’re not merely common, Eddie said. They’re also highly evolvable. They’re protean. They adapt quickly.
Two reasons for that, he explained. It’s not just the high mutation rates but also the fact that their population sizes are huge. “Those two things put together mean you’ll produce more adaptive change.”
RNA viruses replicate speedily, generating their big populations (high titers) of virions within each host. Stated another way, they often produce acute infections, severe for a short time and then gone. Either they soon disappear or they kill you. Eddie called it “this kind of boom-bust thing.” Acute infection also means lots of viral shedding—by way of sneezing or coughing or vomiting or bleeding or diarrhea—which facilitates transmission to other victims. Such viruses try to outrace the immune system of each host, taking what they need and moving onward before a body’s defenses can defeat them. (Lentiviruses, including the HIVs, are exceptional here, following a different strategy.) Their fast replication and high rates of mutation supply them abundantly with genetic variation. Once an RNA virus lands in another host—maybe even another species of host—that abundant variation serves the virus well, giving it many chances to adapt to the new circumstances, whatever those circumstances might be. In some cases it fails to adapt; in some it succeeds well.
Most DNA viruses embody the opposite extremes. Their mutation rates are low and their population sizes can be relatively small. Their strategies of self-perpetuation “tend to go for this persistence route,” Eddie said. Persistence and stealth. They lurk, they wait. They hide from the immune system rather than trying to outrun it. They go dormant and linger within certain cells, replicating little or not at all, sometimes for many years. I knew he was talking about things like varicella zoster virus, a classic DNA virus that begins its infection of humans as chickenpox and can recrudesce, decades later, as shingles. The downside for DNA viruses, Eddie said, is that they can’t adapt so readily to a new species of host. They’re just too stable. Hidebound. Faithful to what has worked in the past.
The stability of DNA viruses derives from the structure of the genetic molecule and how it replicates, using DNA polymerase to assemble and proofread each new strand. The enzyme employed by RNA viruses, on the other hand, is “error prone,” according to Eddie. “It’s just a really crappy polymerase,” which doesn’t proofread, doesn’t backtrack, doesn’t correct erroneous placement of those nucleotide bases, A, C, G, and U. Why not? Because the genomes of RNA viruses are tiny, ranging from about two thousand nucleotides to about thirty thousand, which is much less than what most DNA viruses carry. “It takes more nucleotides,” Eddie said—a larger genome, more information—“to make a new enzyme that works.” One that works as neatly as DNA polymerase does, he meant.
And why are RNA genomes so small? Because their self-replication is so fraught with inaccuracies that, given more information to replicate, they would accumulate more errors and cease to function at all. It’s sort of a chicken-and-egg problem, he said. RNA viruses are limited to small genomes because their mutation rates are so high, and their mutation rates are so high because they’re limited to small genomes. In fact, there’s a fancy name for that bind: Eigen’s paradox. Manfred Eigen is a German chemist, a Nobel winner, who has studied the chemical reactions that yield self-organization of longer molecules, a process that might lead to life. His paradox describes a size limit for such self-replicating molecules, beyond which their mutation rate gives them too many errors and they cease to replicate. They die out. RNA viruses, thus constrained, compensate for their error-prone replication by producing huge populations and achieving transmission early and often. They can’t break through Eigen’s paradox, it seems, but they can scoot around it, making a virtue of their instability. Their copying errors deliver beaucoup variation, and beaucoup variation allows them to evolve fast.
“DNA viruses can make much bigger genomes,” Eddie said. Unlike the RNAs, they’re not limited by Eigen’s paradox. They can even capture and incorporate