Achieving diverse and monoallelic olfactory receptor selection through dual-objective optimization design
Achieving diverse and monoallelic olfactory receptor selection through dual-objective optimization design
复制标题
通过双目标优化设计实现多样化和单等位基因的嗅觉受体选择
DOI：
10.1073/pnas.1601722113
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Xing, Jianhua
中科院分区：
文献类型：
--
作者：
Tian, Xiao-Jun;Zhang, Hang;Sannerud, Jens;Xing, Jianhua
多目标优化在生物系统中很常见。在哺乳动物嗅觉系统中，每个感觉神经元随机地只表达多达数千个嗅觉受体（OR）基因等位基因中的一个；在机体水平上，表达的ORs的类型需要最大化。现有模型仅关注单等位基因激活，无法解释突变体中最近的观察结果，特别是G9a/GLP敲除中表达的ORs的全球多样性降低。在这项工作中，我们整合了关于OR表达的现有信息，并构建了一个基于物理相互作用的综合模型。分析该模型揭示了一个进化优化的三层调控机制，该机制包括区域隔离、表观遗传屏障交叉耦合的负反馈回路，其机制与先前的理论建议不同，以及先前未发现的增强子竞争步骤。该模型不仅概括了单等位基因的OR表达，而且阐明了嗅觉系统如何最大化和维持OR表达的多样性，并有多种预测得到了现有实验结果的验证。通过类比一个具有热激活屏障穿越的物理系统和对比逆向工程分析，揭示了嗅觉受体选择系统是优化设计的，特别强调了协同性和协同性是生物学多目标优化的一般设计原则。
Multiple-objective optimization is common in biological systems. In the mammalian olfactory system, each sensory neuron stochastically expresses only one out of up to thousands of olfactory receptor (OR) gene alleles; at the organism level, the types of expressed ORs need to be maximized. Existing models focus only on monoallele activation, and cannot explain recent observations in mutants, especially the reduced global diversity of expressed ORs in G9a/GLP knockouts. In this work we integrated existing information on OR expression, and constructed a comprehensive model that has all its components based on physical interactions. Analyzing the model reveals an evolutionarily optimized three-layer regulation mechanism, which includes zonal segregation, epigenetic barrier crossing coupled to a negative feedback loop that mechanistically differs from previous theoretical proposals, and a previously unidentified enhancer competition step. This model not only recapitulates monoallelic OR expression, but also elucidates how the olfactory system maximizes and maintains the diversity of OR expression, and has multiple predictions validated by existing experimental results. Through making an analogy to a physical system with thermally activated barrier crossing and comparative reverse engineering analyses, the study reveals that the olfactory receptor selection system is optimally designed, and particularly underscores cooperativity and synergy as a general design principle for multiobjective optimization in biology.
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影响因子：
5.3
作者：
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影响因子：
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作者：
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DOI：
--
发表时间：
1992
期刊：
Society of General Physiologists series
影响因子：
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通讯作者：
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影响因子：
10.5
作者：
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通讯作者：
Ray, Anandasankar
DOI：
10.1073/pnas.78.11.6840
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
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通讯作者：
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