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Cryptic variation is caused by the robustness of phenotypes to mutations. Cryptic variation has no effect on phenotypes in a given genetic or environmental background, but it can have effects after mutations or environmental change. Because evolutionary adaptation by natural selection requires phenotypic variation, phenotypically revealed cryptic genetic variation may facilitate evolutionary adaptation. This is possible if the cryptic variation happens to be pre-adapted, or "exapted", to a new environment, and is thus advantageous once revealed. However, this facilitating role for cryptic variation has not been proven, partly because most pertinent work focuses on complex phenotypes of whole organisms whose genetic basis is incompletely understood. Here we show that populations of RNA enzymes with accumulated cryptic variation adapt more rapidly to a new substrate than a population without cryptic variation. A detailed analysis of our evolving RNA populations in genotype space shows that cryptic variation allows a population to explore new genotypes that become adaptive only in a new environment. Our observations show that cryptic variation contains new genotypes pre-adapted to a changed environment. Our results highlight the positive role that robustness and epistasis can have in adaptive evolution. 相似文献
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Rasmussen SG Choi HJ Fung JJ Pardon E Casarosa P Chae PS Devree BT Rosenbaum DM Thian FS Kobilka TS Schnapp A Konetzki I Sunahara RK Gellman SH Pautsch A Steyaert J Weis WI Kobilka BK 《Nature》2011,469(7329):175-180
G protein coupled receptors (GPCRs) exhibit a spectrum of functional behaviours in response to natural and synthetic ligands. Recent crystal structures provide insights into inactive states of several GPCRs. Efforts to obtain an agonist-bound active-state GPCR structure have proven difficult due to the inherent instability of this state in the absence of a G protein. We generated a camelid antibody fragment (nanobody) to the human β(2) adrenergic receptor (β(2)AR) that exhibits G protein-like behaviour, and obtained an agonist-bound, active-state crystal structure of the receptor-nanobody complex. Comparison with the inactive β(2)AR structure reveals subtle changes in the binding pocket; however, these small changes are associated with an 11?? outward movement of the cytoplasmic end of transmembrane segment 6, and rearrangements of transmembrane segments 5 and 7 that are remarkably similar to those observed in opsin, an active form of rhodopsin. This structure provides insights into the process of agonist binding and activation. 相似文献
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对于汽车等面向消费者的行业,数据驱动的产品开发是一项关键的系统工程。数据驱动方法的前提是数据本身,由于现代车辆的联网能力不断提高,使得汽车制造商能够以内部总线信号的形式记录并储存客户数据。由于这些数据并不用于外部,只用于内部通信以保证车辆的安全性和功能性,这给这些数据的应用带来了一定的困难,因此汽车行业的主要问题在于如何利用数据挖掘技术从这些数据中提取客户需求及相关信息。为此,对上述数据应用问题进行了文献调研,并在此基础上开展数据挖掘的模拟研究,以确定现有数据挖掘过程在需求获取领域的适用性;进而提出一种扩展程序,使得数据挖掘技术能够应用于相关客户数据之中,从而加快车辆开发的进程。 相似文献
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Benjamin Förthmann Hella Brinkmann Andreas Ratzka Michal K. Stachowiak Claudia Grothe Peter Claus 《Cellular and molecular life sciences : CMLS》2013,70(14):2555-2568
Reduced levels of survival of motoneuron (SMN) protein lead to spinal muscular atrophy, but it is still unknown how SMN protects motoneurons in the spinal cord against degeneration. In the nucleus, SMN is associated with two types of nuclear bodies denoted as gems and Cajal bodies (CBs). The 23 kDa isoform of fibroblast growth factor-2 (FGF-223) is a nuclear protein that binds to SMN and destabilizes the SMN-Gemin2 complex. In the present study, we show that FGF-223 depletes SMN from CBs without affecting their general structure. FRAP analysis of SMN-EGFP in CBs demonstrated that the majority of SMN in CBs remained mobile and allowed quantification of fast, slow and immobile nuclear SMN populations. The potential for SMN release was confirmed by in vivo photoconversion of SMN-Dendra2, indicating that CBs concentrate immobile SMN that could have a specialized function in CBs. FGF-223 accelerated SMN release from CBs, accompanied by a conversion of immobile SMN into a mobile population. Furthermore, FGF-223 caused snRNP accumulation in CBs. We propose a model in which Cajal bodies store immobile SMN that can be mobilized by its nuclear interaction partner FGF-223, leading to U4 snRNP accumulation in CBs, indicating a role for immobile SMN in tri-snRNP assembly. 相似文献
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Lucas Matt Stylianos Michalakis Franz Hofmann Verena Hammelmann Andreas Ludwig Martin Biel Thomas Kleppisch 《Cellular and molecular life sciences : CMLS》2011,68(1):125-137
Neuronal hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are known to modulate spontaneous activity, resting
membrane potential, input resistance, afterpotential, rebound activity, and dendritic integration. To evaluate the role of
HCN2 for hippocampal synaptic plasticity, we recorded long-term potentiation (LTP) in the direct perforant path (PP) to CA1
pyramidal cells. LTP was enhanced in mice carrying a global deletion of the channel (HCN2−/−) but not in a pyramidal neuron-restricted knockout. This precludes an influence of HCN2 located in postsynaptic pyramidal
neurons. Additionally, the selective HCN blocker zatebradine reduced the activity of oriens-lacunosum moleculare interneurons
in wild-type but not HCN2−/− mice and decreased the frequency of spontaneous inhibitory currents in postsynaptic CA1 pyramidal cells. Finally, we found
amplified LTP in the PP of mice carrying an interneuron-specific deletion of HCN2. We conclude that HCN2 channels in inhibitory
interneurons modulate synaptic plasticity in the PP by facilitating the GABAergic output onto pyramidal neurons. 相似文献