Reverse Watson-Crick base pairs

While the Watson-Crick (WC) base pairs (bps) are best-known and most abundant in nucleic acid structures (including RNA), the so-called reverse WC bp variants have received little attention. In the well-established Saenger scheme (see figure below), there are 28 possible bps for A, G, U(T), and C in their cononical (keto- and amino-) tautomeric forms and involving at least two H-bonds. The reverse A·T/U and G·C WC pairs are asymmetric, and are numbered XXI and XXII respectively (middle of right-hand side in the figure below).

The 28 possible base-pairs for A, G, U(T), and C involving at least two (cyclic) hydrogen bonds.

In 3DNA, the WC bps are of type M–N and listed as A–T and G–C, consistent with the conventional notation. The reverse WC bps, on the other hand, are of type M+N and listed as A+T and G+C; the ‘+’ signifies the parallel z-axes of the two base reference frames, therefore their dot product is positive (see figure 2 in post Hoogsteen and reverse Hoogsteen base pairs).

As of this writing, a Google search of the phrase “reverse Watson Crick base pair” does not come up with anything informative — the top hit is the Jena Library page titled Nucleic Acid Nomenclature and Structure showing the same set of 28 possible bps only with explicit base chemical structures, as compiled by Tinoco Jr. et al. (1993).

However, once I look into this special type of bps, a quick search in PDB entry 1jj2, the Haloarcula marismortui large ribosomal subunit solved at 2.4 Å resolution, revealed nine reverse WC bps as shown below:

 __U.U..0.205._   __A.A..0.437._   [U+A]
 __C.C..0.1186._  __G.G..0.1190._  [C+G]
 __C.C..0.1377._  __G.G..0.1683._  [C+G]
 __C.C..0.1856._  __G.G..0.1873._  [C+G]
 __A.A..0.2054._  __U.U..0.2648._  [A+U]
 __U.U..0.2109._  __A.A..0.2467._  [U+A]
 __A.A..0.2301._  __U.U..0.2306._  [A+U]
 __A.A..0.2321._  __U.U..0.2378._  [A+U]
 __C.C..0.2510._  __G.G..0.2564._  [C+G] 

The following figure shows a representative reverse WC A+U bp (0.A437 with 0.U205, top), and a representative reverse WC G+C bp (0.G1683 with 0.C1377, bottom). For easy comparison, the two reverse WC bps are orientated in the reference frames of A and G, respectively.

reverse Watson-Crick A+U pair
reverse Watson-Crick G+C pair

In future releases of 3DNA, presumably starting from v2.2, we plan to provide a new component to classify bps according to the Saenger scheme, the Leontis/Westhof notation, and the geometric parameter-based strategy. Overall, the three bp classification methods are complementary in functionality, but with increased sophistication and applicability.



Dear Dr. Lu,
I wish to bring your attention to one of the papers from my PhD work, where we have done extensive database analysis as well as quantum chemical studies on all possible combinations of reverse Watson-Crick base pairs in RNA.
The paper is “Quantum chemical studies of structures and binding in noncanonical RNA base pairs: the trans Watson-Crick:Watson-Crick family”, Journal of biomolecualr structure and dynamics, 25(6), 709-732 (2008).
Of course, since Leontis-Westhof nomenclature is more popular in RNA community, we didn’t use the Saenger’s nomenclature in the paper, which calls these pairs as “Reverse Watson-Crick”. Many of these are found to occur quite freqently in RNA, with A:A pair being the most frequent.

— Purshotam Sharma · 2012-06-22 11:47 · #


Hi Dr. Sharma,

Thanks for your comment. I’ll certainly have a look of your 2008 JBSD paper on reverse Watson-Crick base pairs. Needless to say, the Leontis-Westhof base-pair (bp) nomenclature is popular in the RNA community nowadays, but it's not without limitations. On the other hand, the classic Saenger bp classification is still valid for its targeted purpose. In my opinion, each method has its role to play.

— xiangjun · 2012-06-22 12:10 · #


Dear Dr. Lu,
I’d like to ask a question: if reverse Watson-Crick base pairs belong to the concept “mismatch base pair”?

Welles · 2012-09-06 21:27 · #


In my understanding, the reverse Watson-Crick (WC) base pairs (bps) belong to the concept of “mismatch bp”; the canonical bps include the A-T(U) and G-C WC pairs, and possibly the G-T(U) Wobble pair as well.

The WC (and Wobble) bps are able to form stems, whilst introducing a reverse WC pair would distort the backbone geometry of a double helix.

— xiangjun · 2012-09-06 22:23 · #



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