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PNAS Papers on Disease Gene Selection, Conserved Coronavirus Domain, Horizontal Gene Transfer

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

In a paper slated to appear in PNAS this week, researchers from the US, France, and Germany outline factors influencing negative selection at hundreds of sites linked to inborn errors of immunity (IEI). When the team considered "consensus negative selection" (CoNeS) scores for 366 IEI genes, along with autosomal or X-linked genes associated with Mendelian conditions or inborn errors of neurodevelopment, it saw signs that the extent of negative selection on monogenic IEI genes varied depending on their clinical consequences as well as the type of inheritance involved. Such findings prompted the authors to come up with a supervised classifier known as SCoNeS for predicting recessive or dominant inheritance for autosomal genes involved in disease. "These results," they write, "have evolutionary implications for studies of the drivers of negative selection, and practical implications in the search for genes underlying life-threatening, heritable conditions."

A team from the University of Alabama at Birmingham and Johns Hopkins University takes a look at the structure and potential function of a conserved, ADP ribose-hydrolyzing protein macrodomain in a bat coronavirus (CoV) called HKU4. Using X-ray crystal structure insights, radioactive assay data, and in silico analyses, the researchers characterized the HKU4 macrodomain during interactions with three different small molecule ligands, detecting ADP ribose hydrolase enzyme activity. "It is evident that the [beta-coronaviruses] share common features that can be exploited in the development of antiviral treatments," they write, noting that "[i]f structural and functional features are retained in the [beta-coronavirus] genus as they cross the species barrier, then it is reasonable to suggest that the features described in the paper may be consistent with CoVs that emerge from bats in the future."

From a phylogenomics-based analysis that encompassed many single-gene and multigene trees, investigators in France and Canada describe frequent transfer of bacterial genes — particularly those coding for secreted proteins — into a group of algae called ochrophytes that spans kelp, chrysophytes, and photosynthetic diatoms, including the model diatom species Phaeodactylum tricornutum. "Throughout their history, ochrophytes have exchanged genes with bacteria and eukaryotes through horizontal gene transfer (HGT), diversifying their cell biology," they write. "Here, we profile thousands of phylogenetic trees, showing that HGTs from bacteria contribute to the recent evolutionary success of diatoms following their divergence from other ochrophytes, occurring more frequently than HGTs from eukaryotes and, potentially, more frequently in diatoms than other ochrophytes."