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Adaptive evolution of bat dipeptidyl peptidase 4 (dpp4): implications for the origin and emergence of Middle East respiratory syndrome coronavirus

Jie Cui1*, John-Sebastian Eden1, Edward C Holmes1 and Lin-Fa Wang23

Author Affiliations

1 Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Biological Sciences and Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia

2 Duke-NUS Graduate Medical School, Singapore 169857, Singapore

3 CSIRO Livestock Industries, Australian Animal Health Laboratory, Geelong, VIC 3220, Australia

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Virology Journal 2013, 10:304  doi:10.1186/1743-422X-10-304

Published: 10 October 2013



The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) that first appeared in Saudi Arabia during the summer of 2012 has to date (20th September 2013) caused 58 human deaths. MERS-CoV utilizes the dipeptidyl peptidase 4 (DPP4) host cell receptor, and analysis of the long-term interaction between virus and receptor provides key information on the evolutionary events that lead to the viral emergence.


We show that bat DPP4 genes have been subject to significant adaptive evolution, suggestive of a long-term arms-race between bats and MERS related CoVs. In particular, we identify three positively selected residues in DPP4 that directly interact with the viral surface glycoprotein.


Our study suggests that the evolutionary lineage leading to MERS-CoV may have circulated in bats for a substantial time period.

MERS-CoV; Bats; Arms-race; Adaptive evolution; Emergence