Rahul Kohli and colleagues focus on cytosine, one of the four chemical “bases” that comprise the alphabet that the genetic material DNA uses to spell out everything from hair and eye color to risk of certain diseases. But far from just storing information, cytosine has acquired a number of other functions that give it a claim to being the genome's wild card.

“In poker, the rules of the game can occasionally change,” they note in the article. “Adding a 'wild card' to the mix introduces a new degree of variety and presents opportunities for a skilled player to steal the pot. Given that evolution is governed by the same principles of risk and reward that are common to a poker game, it is perhaps not surprising that a genomic 'wild card' has an integral role in biology.”

They discuss the many faces of cytosine that make it such a game-changer and the biological processes that help to change its identity. Removing something called an amine group from cytosine, for instance, allows the immune system to recognize and destroy foreign invaders such as viruses. Adding so-called “methyl groups” on cytosines acts as on/off switches for genes. The authors say that these many faces of cytosine allow it to play various roles and give it true “wild card” status.

The authors acknowledge funding from the Rita Allen Foundation, the W.W. Smith Charitable Trust and the National Institutes of Health.

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