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This Week in PNAS: May 7, 2019

Researchers from the University of Copenhagen and elsewhere describe relationships between individuals in an ancient mass grave associated with the so-called Globular Amphora culture, which once spanned a large swath of Central and Eastern Europe. Starting with a 5,000-year-old mass grave in present-day Poland, the team identified 15 skeletons from men, women, and children who appeared to have suffered fatal blows to the head. With genome sequencing done to average depths of one- to nearly fourfold, the investigators found that the individuals belonged to a large family that did not have steppe-related ancestry associated with a nearby Corded Ware culture. "Although the reason for the massacre is unknown, it is possible that it was connected with the expansion of Corded Ware groups," the authors say, "which may have resulted in violent conflict." 

An international team led by investigators in the UK and France suggest that climate change-related range loss projections may be over-estimated for some species if adaptive genetic variations are not taken into account. The researchers used double digest, restriction site-associated DNA sequencing to find tens of thousands of informative SNPs in hundreds of forest bats from two cryptic species — Myotis escalerai and M. crypticus — used in their genotype- and population structure-informed analyses of range loss predictions and possible evolutionary rescue of climate change vulnerability. Their results hint that adaptive variation may mitigate some range losses, though new overlap and competition between similar species in the future are expected to influence this rescue as well. "We show that although evolutionary rescue is possible, it depends on a population's adaptive capacity and connectivity," they report. "Hence, we stress the importance of incorporating genomic data and landscape connectivity in climate change vulnerability assessments and conservation management."

Japanese researchers attempt to characterize variants of unknown significance in the EGFR gene that might influence response to EGFR-tyrosine kinase inhibitor (TKI) drug response in individuals with non-small cell lung carcinoma. When the team assessed nearly 3,800 EGFR hotspot mutation-free NSCLC cases, it found that some 5.5 percent had rare somatic EGFR mutations, though most of those patients did not receive first-line TKI treatment. The authors went on to use a molecular dynamics simulation model for predicting EGFR-TKI sensitivity for such rare EGFR tumor mutations, demonstrating that that the approach could pick up alterations linked to TKI sensitivity in vitro and in vivo. "The findings suggest the usefulness of in silico simulation to overcome mutation diversity at a clinical relevant level," they write, adding that the "present in silico model will help in selecting effective drugs for these patients."