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Deoxyinosine: Don’t call me a universal base!

According to Nobel Laureate Michael Smith, deoxyinosine is not a universal base. Read why.

Deoxyinosine, a naturally occurring nucleoside, was considered the first “universal” base—meaning that it could base pair with the other natural DNA bases: A, C, G, and T. However, this terminology encountered some criticism, notably from Dr. Michael Smith, winner of the Nobel Prize in Chemistry in 1993 for developing site-directed mutagenesis, who mentioned deoxyinosine in his Nobel lecture.

"I have always been puzzled by the widespread acceptance of the idea that deoxyinosine is precocious in base pairing because inosine behaves in a precocious manner in t-RNA duplex interactions. Studies on deoxyinosine, in fact, indicate that it functions as a specific analog of deoxyguanosine, although it does not self-aggregate as does deoxyguanosine.”

Subsequent studies have shown that Dr. Smith was correct: deoxyinosine binds preferably to deoxycytidine (dC) [1]. So go ahead and use it in experiments, just don’t call it universal!


1. Watkins NE, Jr., SantaLucia J, Jr. Nearest-neighbor thermodynamics of deoxyinosine pairs in DNA duplexes. Nucleic Acids Res. 2005;33(19):6258-67. doi:10.1093/nar/gki918

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Published Jun 15, 2012
Revised/updated Apr 27, 2023