Mutualistic symbiosis and eusociality have developed through gradual evolutionary processes at different times in specific lineages. Like some species of termites and ants, ambrosia beetles have independently evolved a mutualistic nutritional symbiosis with fungi, which has been associated with the evolution of complex social behaviors in some members of this group. We sequenced the transcriptomes of two ambrosia complexes (Euwallacea sp. near fornicatus⁻Fusarium euwallaceae and Xyleborus glabratus⁻Raffaelea lauricola) to find evolutionary signatures associated with mutualism and behavior evolution. We identified signatures of positive selection in genes related to nutrient homeostasis; regulation of gene expression; development and function of the nervous system, which may be involved in diet specialization; behavioral changes; and social evolution in this lineage. Finally, we found convergent changes in evolutionary rates of proteins across lineages with phylogenetically independent origins of sociality and mutualism, suggesting a constrained evolution of conserved genes in social species, and an evolutionary rate acceleration related to changes in selective pressures in mutualistic lineages.

The assessment of measurable residual disease (MRD) in bone marrow has proven of prognostic relevance in patients with multiple myeloma (MM). Nevertheless, and unlike other hematologic malignancies, the use of MRD results to make clinical decisions in MM has been underexplored to date. In this retrospective study, we present the results from a multinational and multicenter series of 400 patients with MRD monitoring during front-line therapy with the aim of exploring how clinical decisions made based on those MRD results affected outcomes. As expected, achievement of MRD negativity at any point was associated with improved PFS versus persistent MRD positivity (median PFS 104 vs. 45 months, p < 0.0001). In addition, however, 67 out of 400 patients underwent a clinical decision (treatment discontinuation, intensification or initiation of a new therapy) based on MRD results. Those patients in whom a treatment change was made showed a prolonged PFS in comparison with those 333 patients in which MRD results were not acted upon (respectively, mPFS 104 vs. 62 months, p = 0.005). In patients who achieved MRD negativity during maintenance (n = 186) on at least one occasion, stopping therapy in 24 patients vs. continuing in 162 did not alter PFS (mPFS 120 months vs. 82 months, p = 0.1). Most importantly, however, in patients with a positive MRD during maintenance (n = 214), a clinical decision (either intensification or change of therapy) (n = 43) resulted in better PFS compared to patients in whom no adjustment was made (n = 171) (mPFS NA vs. 39 months, p = 0.02). Interestingly, there were no significant differences when MRD was assessed by flow cytometry or by next-generation sequencing. Herein, we find that MRD is useful in guiding clinical decisions during initial therapy and has a positive impact on PFS in MM patients. This potentially opens a new dimension for the use of MRD in MM, but this role still remains to be confirmed in prospective, randomized clinical trials.