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Kussmann, J.

Publications and source records attributed to Kussmann, J..

2 recordsLinked to original sources

Soil heterogeneity and pleiotropy contribute to polygenic soil adaptation during postglacial range expansion in an alpine plant

1) Plants colonized new abiotic environments during postglacial range expansions. Little is known about whether populations adapt to different soil conditions during range expansion and, if so, which mechanisms underlie presumably polygenic adaptation. It remains unclear how pleiotropy and soil heterogeneity contribute to such adaptation. 2) We studied 43 populations of Dianthus sylvestris with characterized soil conditions along its postglacial range expansion in the Alps. We leveraged genome-wide data and variation in multiple soil variables to identify polygenic signatures of selection in soil-associated alleles using environmental association analysis, generalized dissimilarity models, and polygenic scores. 3) We found signatures of selection in 814 single nucleotide polymorphisms (SNPs) and the largest magnitude of allele frequency change in candidate SNPs associated with K, Mg, and Al. Candidate genes showed higher pleiotropy than randomly sampled genes. We found soil heterogeneity shaping the populations adaptive genetic variation in the landscape. 4) Our results suggest that populations of D. sylvestris adapted to contrasting soil chemical properties during postglacial range expansion through polygenic adaptation. Pleiotropy likely plays an important role in polygenic adaptation to novel selective pressures and soil heterogeneity is an important factor contributing to the maintenance of adaptive genetic variation.

evolutionary biology↗

QM/MM Free Energy Calculations of Long-Range Biological Protonation Dynamics by Adaptive and Focused Sampling

Water-mediated proton transfer reactions are central for catalytic processes in a wide range of biochemical systems, ranging from biological energy conversion to chemical transformations in the metabolism. Yet, the accurate computational treatment of such complex bio-chemical reactions is highly challenging and requires the application of multiscale methods, in particular hybrid quantum/classical (QM/MM) approaches combined with free energy simulations. Here we combine the unique exploration power of new advanced sampling methods with density functional theory (DFT)-based QM/MM free energy methods for multiscale simulations of long-range protonation dynamics in biological systems. In this regard, we show that combining multiple walkers/well-tempered metadynamics with an extended-system adaptive biasing force method (MWE), provides a powerful approach for exploration of water-mediated proton transfer reactions in complex biochemical systems. We compare and combine the MWE method also with QM/MM-umbrella sampling and explore the sampling of the free energy landscape with both geometric (linear combination of proton transfer distances) and physical (center of excess charge) reaction coordinates, and show how these affect the convergence of the potential of mean force (PMF) and the activation free energy. We find that the QM/MM-MWE method can efficiently explore both direct and water-mediated proton transfer pathways together with forward and reverse hole transfer mechanisms in the highly complex proton channel of respiratory Complex I, while the QM/MM-US approach shows a systematic convergence of selected long-range proton transfer pathways. In this regard, we show that the PMF along multiple proton transfer pathways is recovered by combining the strengths of both approaches in a QM/MM-MWE/focused US (FUS) scheme, and revealing new mechanistic insight into the proton transfer principles of Complex I. Our findings provide a promising basis for the quantitative multi-scale simulations of long-range proton transfer reactions in biological systems.

biophysics↗