Parallel evolution of the G protein-coupled receptor GrlG and the loss of fruiting body formation in the social amoeba Dictyostelium discoideum evolved under low relatedness.

Aggregative multicellularity relies on cooperation among formerly independent cells to form a multicellular body. Previous work with Dictyostelium discoideum showed that experimental evolution under low relatedness profoundly decreased cooperation, as indicated by the loss of fruiting body formation in many clones and an increase of cheaters that contribute proportionally more to spores than to the dead stalk. Using whole-genome sequencing and variant analysis of these lines, we identified 38 single nucleotide polymorphisms in 29 genes. Each gene had 1 variant except for grlG (encoding a G protein-coupled receptor), which had 10 unique SNPs and 5 structural variants. Variants in the 5' half of grlG-the region encoding the signal peptide and the extracellular binding domain-were significantly associated with the loss of fruiting body formation; the association was not significant in the 3' half of the gene. These results suggest that the loss of grlG was adaptive under low relatedness and that at least the 5' half of the gene is important for cooperation and multicellular development. This is surprising given some previous evidence that grlG encodes a folate receptor involved in predation, which occurs only during the single-celled stage. However, non-fruiting mutants showed little increase in a parallel evolution experiment where the multicellular stage was prevented from happening. This shows that non-fruiting mutants are not generally selected by any predation advantage but rather by something-likely cheating-during the multicellular stage.

External validation of GO-FAR 2 calculator for outcomes after in-hospital cardiac arrest with comparison to GO-FAR and trial of expanded applications.

Aim: Externally validate the GO-FAR 2 tool for predicting survival with good neurologic function after in-hospital cardiac arrest with comparison to the original GO-FAR tool. Additionally, we collected qualitative descriptors and performed exploratory analyses with various levels of neurologic function and discharge destination. Methods: Retrospective chart review of all patients who underwent in-hospital resuscitation after cardiac arrest during the calendar years 2016-2019 in our institution (n = 397). GO-FAR and GO-FAR 2 scores were calculated based on information available in the medical record at the time of hospital admission. Cerebral performance category (CPC) scores at the time of admission and discharge were assessed by chart review. Results: The GO-FAR 2 score accurately predicted outcomes in our study population with a c-statistic of 0.625. The original GO-FAR score also had accurate calibration with a stronger c-statistic of 0.726. The GO-FAR score had decreased predictive value for lesser levels of neurologic function (c-statistic 0.56 for alive at discharge) and discharge destination (0.69). Descriptors of functional status by CPC score were collected. Conclusion: Our findings support the validity of the GO-FAR and GO-FAR 2 tools as published, but the c-statistics suggest modest predictive discrimination. We include functional descriptors of CPC outcomes to aid clinicians in using these tools. We propose that information about expected outcomes could be valuable in shared decision-making conversations.