Transmission of SARS-CoV-2 in domestic cats imposes a narrow bottleneck

The evolutionary mechanisms by which SARS-CoV-2 viruses adapt to mammalian hosts and, potentially, escape human immunity depend on the ways genetic variation is generated and selected within and between individual hosts. Using domestic cats as a model, we show that SARS-CoV-2 consensus sequences remain largely unchanged over time within hosts, but dynamic sub-consensus diversity reveals processes of genetic drift and weak purifying selection. Transmission bottlenecks in this system appear narrow, with new infections being founded by fewer than ten viruses. We identify a notable variant at amino acid position 655 in Spike (H655Y) which arises rapidly in index cats and becomes fixed following transmission in two of three pairs, suggesting this site may be under positive selection in feline hosts. We speculate that narrow transmission bottlenecks and the lack of pervasive positive selection combine to constrain the pace of ongoing SARS-CoV-2 adaptive evolution in mammalian hosts.