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PNAS Papers on SARS-CoV-2 Adaptation in Animals, Transcription Factor Dynamics, Fin Formation

Editor's Note: Some of the articles described below are not yet available at the PNAS site but are scheduled to be posted this week.

A team from Colorado State University and the University of Pennsylvania tracks SARS-CoV-2 adaptation and variant selection in several non-human animals, including half a dozen cats, three dogs, three hamsters, and a ferret. After expanding the human SARS-CoV-2 strain USA-WA1/2020 in cell culture in the lab, the researchers used whole-genome sequencing to assess viral sequences found in animals exposed to the strain, uncovering wild type reversion mutations and more than a dozen variants in sequences coding for the SARS-CoV-2 spike protein and other genes. "We report the surprisingly rapid selection of numerous SARS-CoV-2 variants in cell culture and following infection of non-human mammalian hosts, including dogs and cats," the authors report. "These molecular changes in SARS-CoV-2provide insight into mechanisms of viral host adaptation, lay the groundwork for additional studies assessing dominant variant fitness and phenotype, and highlight the potential for human reinfection with new viral variants arising in species in close and frequent contact with humans."

Harvard Medical School researchers profile SP1 transcription factor binding in the human genome over time using chromatin immunoprecipitation sequencing in a tamoxifen-inducible ChIP-seq system and cells with a version of SP1 linked to the binding domain of the estrogen receptor. "SP1 is a transcriptional activator protein that binds GC-box DNA sequences at many promoter and enhancer regions," the authors say, noting that their time course experiments highlight the dynamic nature of its target site binding patterns. "SP1 rapidly reaches maximal binding levels at some sites, but binding kinetics at other sites is biphasic, with rapid half-maximal binding followed by a considerably slower increase to maximal binding," they report. "We describe the molecular parameters that distinguish between these different classes of SP1 binding sites."

Using CRISPR-Cas9-based gene editing and other experiments in the medaka fish, Oryzias latipes, a team from Spain, Chile, and the US dug into the regulatory features underlying fin formation in vertebrates, focusing in on a SHH-GLI pathway that contributes to unpaired dorsal fin, paired fin, and tetrapod limb formation­. "Our molecular and genetic analyses indicate that the size of fish fins in controlled by an ancient mechanism mediated by SHH-GLI signaling that appeared prior to the evolutionary appearance of paired fins," they write. "We also show that the key regulatory networks that mediate the expansion of digit progenitor cells in tetrapods were already in place in the fins of the last common ancestor between ray and lobe-finned fishes, suggesting an ancient similarity between distal fins and digits."