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Thermodynamic System Drift in Protein Evolution
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نویسنده
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hart k.m. ,harms m.j. ,schmidt b.h. ,elya c. ,thornton j.w. ,marqusee s.
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منبع
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plos biology - 2014 - دوره : 12 - شماره : 11
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چکیده
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Proteins from thermophiles are generally more thermostable than their mesophilic homologs,but little is known about the evolutionary process driving these differences. here we attempt to understand how the diverse thermostabilities of bacterial ribonuclease h1 (rnh) proteins evolved. rnh proteins from thermus thermophilus (ttrnh) and escherichia coli (ecrnh) share similar structures but differ in melting temperature (tm) by 20°c. ttrnh's greater stability is caused in part by the presence of residual structure in the unfolded state,which results in a low heat capacity of unfolding (δcp) relative to ecrnh. we first characterized rnh proteins from a variety of extant bacteria and found that tm correlates with the species' growth temperatures,consistent with environmental selection for stability. we then used ancestral sequence reconstruction to statistically infer evolutionary intermediates along lineages leading to ecrnh and ttrnh from their common ancestor,which existed approximately 3 billion years ago. finally,we synthesized and experimentally characterized these intermediates. the shared ancestor has a melting temperature between those of ttrnh and ecrnh; the tms of intermediate ancestors along the ttrnh lineage increased gradually over time,while the ecrnh lineage exhibited an abrupt drop in tm followed by relatively little change. to determine whether the underlying mechanisms for thermostability correlate with the changes in tm,we measured the thermodynamic basis for stabilization—δcp and other thermodynamic parameters—for each of the ancestors. we observed that,while the tm changes smoothly,the mechanistic basis for stability fluctuates over evolutionary time. thus,even while overall stability appears to be strongly driven by selection,the proteins explored a wide variety of mechanisms of stabilization,a phenomenon we call “thermodynamic system drift.” this suggests that even on lineages with strong selection to increase stability,proteins have wide latitude to explore sequence space,generating biophysical diversity and potentially opening new evolutionary pathways. © 2014 hart et al.
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آدرس
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department of chemistry,university of california,berkeley,berkeley,ca,united states,institute for quantitative biosciences (qb3),university of california,berkeley,berkeley,ca, United States, institute of molecular biology,university of oregon,eugene,or, United States, institute for quantitative biosciences (qb3),university of california,berkeley,berkeley,ca,united states,department of molecular & cell biology,university of california,berkeley,berkeley,ca,united states,department of biochemistry and biophysics,university of san francisco school of medicine,san francisco,ca, United States, institute for quantitative biosciences (qb3),university of california,berkeley,berkeley,ca,united states,department of molecular & cell biology,university of california,berkeley,berkeley,ca, United States, department of human genetics and department of ecology and evolution,university of chicago,chicago,il, United States, institute for quantitative biosciences (qb3),university of california,berkeley,berkeley,ca,united states,department of molecular & cell biology,university of california,berkeley,berkeley,ca, United States
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Authors
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