Species richness is greatest in the tropics, and much of this diversity is concentrated in mountains. Janzen proposed that reduced seasonal temperature variation selects for narrower thermal ...tolerances and limited dispersal along tropical elevation gradients Janzen DH (1967) Am Nat 101:233–249. These locally adapted traits should, in turn, promote reproductive isolation and higher speciation rates in tropical mountains compared with temperate ones. Here, we show that tropical and temperate montane stream insects have diverged in thermal tolerance and dispersal capacity, two key traits that are drivers of isolation in montane populations. Tropical species in each of three insect clades have markedly narrower thermal tolerances and lower dispersal than temperate species, resulting in significantly greater population divergence, higher cryptic diversity, higher tropical speciation rates, and greater accumulation of species over time. Our study also indicates that tropical montane species, with narrower thermal tolerance and reduced dispersal ability, will be especially vulnerable to rapid climate change.
Chemotherapy is used to treat most cancer patients, yet our understanding of factors that dictate response and resistance to such drugs remains limited. We report the generation of a quantitative ...chemical-genetic interaction map in human mammary epithelial cells charting the impact of the knockdown of 625 genes related to cancer and DNA repair on sensitivity to 29 drugs, covering all classes of chemotherapy. This quantitative map is predictive of interactions maintained in other cell lines, identifies DNA-repair factors, predicts cancer cell line responses to therapy, and prioritizes synergistic drug combinations. We identify that ARID1A loss confers resistance to PARP inhibitors in cells and ovarian cancer patients and that loss of GPBP1 causes resistance to cisplatin and PARP inhibitors through the regulation of genes involved in homologous recombination. This map helps navigate patient genomic data and optimize chemotherapeutic regimens by delineating factors involved in the response to specific types of DNA damage.
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•Chemotherapy genetic interaction map covering 625 genes and 29 DNA-damaging agents•Map predicts cancer cell line drug responses and synergistic drug combinations•ARID1A loss confers PARP inhibitor resistance in cells and ovarian cancer patients•GPBP1 loss confers PARP inhibitor resistance via regulation of HR gene expression
Hu et al. map the impact of knockdown of 625 cancer and DNA repair genes on the cellular response to every class of chemotherapy. This map can be used to predict drug responses and identify synergistic drug combinations, and it reveals two factors, ARID1A and GPBP1, whose loss contributes to PARP inhibitor resistance.
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