Thursday, September 19, 2013

Recombinomics: Riyadh_1 Recombinant Destroys MERS Molecular Clock

September 18, 2013
The Kingdom of Saudi Arabia Ministry of Health (KSA-MoH) released 45 MERS-CoV sequences, including full sequences from 13 cases.  One of the sequences, Bisha_1_2012 was from the same patient (60M) as the first public sequence, EMC/12.  However, the two sequences were from easily distinguished sub-clades indicating the first confirmed MERS case was infected by at least two distinct MERS coronvairuses.  Moreover, the Bisha_1 sequences had clear evidence for recombination, with the 5’ end donated by England1 –like parent and the 3’ end from an Al Hasa –like parent.  The recombination events, as well as the clustering of polymorphisms shared by EMC/12 and Jordan-N3 in ORF1ab, signaled additional recombination which would serious damage a near term molecular clock.
Another full sequence released by KSA-MoH was Riyadh_1_2012 which was collected on October 23, which would correspond to the hospitalization date for the first reported MERS-CoV case from Riyadh, a45M gym teacher who fully recovered (after a month in the hospital which included kidney failure and dialysis).  The collection date was more than 4 months after the collection date for Bisha_1_2010 (June 19), but the more than 30,000 BP sequences were virtually identical (Riyadh_1 had A75T).  This identity included a 17 BP deletion at position 26561.  Thus, the identities between the two sequences from samples collected 4 months apart at well separated locations, also seriously limits the use of a molecular clock for the determination of a near term jump of MERS to humans.
Similarly, the identical cross-over points for the recombination signals clonal expansion of recombinants, which are commonly found in human MERS-CoV sequences.

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