Analysis of intrapatient heterogeneity uncovers the microevolution of Middle East respiratory syndrome coronavirus

Park, Donghyun; Huh, Hee Jae; Kim, Yeon Jeong; Son, Dae-Soon; Jeon, Hyo-Jeong; Im, Eu-Hyun; Kim, Jong-Won; Lee, Nam Yong; Kang, Eun-Suk; Kang, Cheol In; Chung, Doo Ryeon; Ahn, Jin-Hyun; Peck, Kyong Ran; Choi, Sun Shim; Kim, Yae-Jean; Ki, Chang-Seok; Park, Woong-Yang

Because most of the mixed bases observed in Patient 14 were not completely fixed in the subsequent generation of cases, the single-nucleotide variants might not have had significantly higher fitness than wild type. For example, the sequence from Patient 14 had a mixed base C/T at position 11257. Among sequences from patients exposed to Patient 14, a subset displayed either C or T alone with little intrapatient heterogeneity, whereas others showed similar intrapatient heterogeneity to Patient 14. In addition, we could not find any significant differences in genetic variants based on disease severity group (Supplemental Tables S3 and S4 ). Taken together, genetic variant composition in each patient varied, regardless of the transmissibility or disease severity, suggesting that transmission of individual genetic sequences was stochastic rather than selective. Even if the genetic variants had a selective advantage, the advantage of individual genetic sequences might have been weak and/or varied depending on the patient.