Extensive Recombination In Human Hafr Al Batin MERS

Wednesday, September 18, 2013
By Paul Martin

September 18, 2013

The Kingdom of Saudi Arabia Ministry of Health (KSA-MoH) released 45 MERS-CoV sequences, including full sequences from 13 cases. The Bisha_1_2012 sequence was from the same patient (60M) as the EMC/12 sequence, but each sequence represented easily distinguished sub-clades indicating the patient was infected by two or more MERS coronaviruses.

The Bisha_1 sequence was an obvious recombinant, and the sequence was virtually identical to Riyadh_1_2012, which was collected 4 months after the Bisha case, signaling faithful replication and evolution via homologous recombination.

However, the most dramatic example of recombination was in the Hafr-Al-Batin_1_2013 sequence which was collected on June 4, 2013. The sequence had clear clustering of polymorphisms from four different parents. Positions 542-1833 had 5 polymorphisms shared with Jordan-N3. The sequence between positions 3276-19418 then switch to an Al Hasa sequence with 8 polymorphisms shared with Al Hasa 1-4. The sequence then changed again with 3 UAE polymorphisms between 20848 and 22895. The sequence then switched back to Al Hasa with 6 polymorphisms between 23648 and 24740. The 3’ end of the genome had 6 England1 polymorphisms between positions 25052 and 29853.

This switching from one human MERS parent to another across the entire genome raises concerns that the level of human MERS is markedly higher than reflected in the confirmed cases. The two distinct sequences from the first confirmed case in KSA in June, 2012 and the extensive recombination in a sequence from a June 2013 case signal rapid evolution and adaptation by human coronaviruses, which highlights the need for more active surveillance and sequences in KSA and adjacent countries.

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