Mutation is a primary source of genetic variation that is used to power evolution.Many studies,however,have shown that most mutations are deleterious and,as a result,extremely low mutation rates might be benefcial for...Mutation is a primary source of genetic variation that is used to power evolution.Many studies,however,have shown that most mutations are deleterious and,as a result,extremely low mutation rates might be benefcial for survival.Using a mutation accumulation experiment,an unbiased method for mutation study,we found an extremely low base-substitution mutation rate of 5.94×10^(-11) per nucleotide site per cell division(95%Poisson confdence intervals:4.65×10^(-11),7.48×10^(-11))and indel mutation rate of 8.25×10^(-12) per site per cell division(95%confdence intervals:3.96×10^(-12),1.52×10^(-11))in the bacterium Photorhabdus luminescens ATCC29999.The mutations are strongly A/T-biased with a mutation bias of 10.28 in the A/T direction.It has been hypothesized that the ability for selection to lower mutation rates is inversely proportional to the efective population size(drift-barrier hypothesis)and we found that the efective population size of this bacterium is signifcantly greater than most other bacteria.This fnding further decreases the lower-bounds of bacterial mutation rates and provides evidence that extreme levels of replication fdelity can evolve within organisms that maintain large efective population sizes.展开更多
The mutation rate used in the previous analyses of pig evolution and demographics was cursory and hence invited potential bias in inferring evolutionary history.Herein,we estimated the de novo mutation rate of pigs as...The mutation rate used in the previous analyses of pig evolution and demographics was cursory and hence invited potential bias in inferring evolutionary history.Herein,we estimated the de novo mutation rate of pigs as 3.6×10-9 per base per generation using high-quality whole-genome sequencing data from nine individuals in a three-generation pedigree through stringent filtering and validation.Using this mutation rate,we re-investigated the evolutionary history of pigs.The estimated divergence time of~10 kiloyears ago(KYA)between European wild and domesticated pigs was consistent with the domestication time of European pigs based on archaeological evidence.However,other divergence events inferred here were not as ancient as previously described.Our estimates suggest that Sus speciation occurred~1.36 million years ago(MYA);European wild pigs split from Asian wild pigs only~219 KYA;and south and north Chinese wild pigs split~25 KYA.Meanwhile,our results showed that the most recent divergence event between Chinese wild and domesticated pigs occurred in the Hetao Plain,northern China,approximately 20 KYA,supporting the possibly independent domestication in northern China along the middle Yellow River.We also found that the maximum effective population size of pigs was~6 times larger than estimated before.An archaic migration from other Sus species originating~2 MYA to European pigs was detected during western colonization of pigs,which may affect the accuracy of previous demographic inference.Our de novo mutation rate estimation and its consequences for demographic history inference reasonably provide a new vision regarding the evolutionary history of pigs.展开更多
The World Health Organization has declared the present Zika virus epidemic to be a 'Public Health Emergency of International Concern'. The virus appears to have spread from Thailand to French Polynesia in 2013, and ...The World Health Organization has declared the present Zika virus epidemic to be a 'Public Health Emergency of International Concern'. The virus appears to have spread from Thailand to French Polynesia in 2013, and has since infected over a million people in the countries of South and Central America. In most cases the infection is mild and transient, but the virus does appear to be strongly neurotropic and the presumptive cause of both birth defects in fetuses and Guillain-Barr6 syndrome in some adults. In this paper, the techniques and utilities developed in the study of mitochondrial DNA were applied to the Zika virus. As a result, it is possible to show in a simple manner how a phylogenetic tree may be constructed and how the mutation rate of the virus can be measured. The study showed the mutation rate to vary between 12 and 25 bases a year, in a viral genome of 10 272 bases. This rapid mutation rate will enable the geographic spread of the epidemic to be monitored easily and may also prove useful in assisting the identification of preventative measures that are working, and those that are not.展开更多
Development of controllable hypermutable cells can greatly benefit understanding and harnessing microbial evolution.However,there have not been any similar sys-tems developed for Clostridium,an important bacterial gen...Development of controllable hypermutable cells can greatly benefit understanding and harnessing microbial evolution.However,there have not been any similar sys-tems developed for Clostridium,an important bacterial genus.Here we report a novel two-step strategy for de-veloping controllable hypermutable cells of Clostridium acetobutylicum,an important and representative indus-trial strain.Firstly,the mutS/L operon essential for methyl-directed mismatch repair(MMR)activity was inactivated from the genome of C.acetobutylicum to generate hy-permutable cells with over 250-fold increased mutation rates.Secondly,a proofreading control system carrying an inducibly expressed mutS/L operon was constructed.The hypermutable cells and the proofreading control system were integrated to form a controllable hypermut-able system SMBMutC,of which the mutation rates can be regulated by the concentration of anhydrotetracycline(aTc).Duplication of the miniPthl-tetR module of the proof-reading control system further signifi cantly expanded the regulatory space of the mutation rates,demonstrating hypermutable Clostridium cells with controllable mutation rates are generated.The developed C.acetobutylicum strain SMBMutC2 showed higher survival capacities than the control strain facing butanol-stress,indicating greatly increased evolvability and adaptability of the controllable hypermutable cells under environmental challenges.展开更多
基金This work is supported by the Young Taishan Scholars Program of Shandong Province(tsqn201812024)the Fundamental Research Funds for the Central Universities of China(201822020)to H.L.+1 种基金the Multidisciplinary University Research Initiative Award from the US Army Research Ofce(W911NF-09-1-0444 and W911NF-09-1-0411)National Institutes of Health award(R35-GM122566)to M.L.
文摘Mutation is a primary source of genetic variation that is used to power evolution.Many studies,however,have shown that most mutations are deleterious and,as a result,extremely low mutation rates might be benefcial for survival.Using a mutation accumulation experiment,an unbiased method for mutation study,we found an extremely low base-substitution mutation rate of 5.94×10^(-11) per nucleotide site per cell division(95%Poisson confdence intervals:4.65×10^(-11),7.48×10^(-11))and indel mutation rate of 8.25×10^(-12) per site per cell division(95%confdence intervals:3.96×10^(-12),1.52×10^(-11))in the bacterium Photorhabdus luminescens ATCC29999.The mutations are strongly A/T-biased with a mutation bias of 10.28 in the A/T direction.It has been hypothesized that the ability for selection to lower mutation rates is inversely proportional to the efective population size(drift-barrier hypothesis)and we found that the efective population size of this bacterium is signifcantly greater than most other bacteria.This fnding further decreases the lower-bounds of bacterial mutation rates and provides evidence that extreme levels of replication fdelity can evolve within organisms that maintain large efective population sizes.
基金This work was financially supported by the Innovative Research Team of the Ministry of Education of China(Grant No.IRT1136)the National Natural Science Foundation of China(Grant No.31672383)the National Swine Industry and Technology System of China(Grant No.nycytx-009).
文摘The mutation rate used in the previous analyses of pig evolution and demographics was cursory and hence invited potential bias in inferring evolutionary history.Herein,we estimated the de novo mutation rate of pigs as 3.6×10-9 per base per generation using high-quality whole-genome sequencing data from nine individuals in a three-generation pedigree through stringent filtering and validation.Using this mutation rate,we re-investigated the evolutionary history of pigs.The estimated divergence time of~10 kiloyears ago(KYA)between European wild and domesticated pigs was consistent with the domestication time of European pigs based on archaeological evidence.However,other divergence events inferred here were not as ancient as previously described.Our estimates suggest that Sus speciation occurred~1.36 million years ago(MYA);European wild pigs split from Asian wild pigs only~219 KYA;and south and north Chinese wild pigs split~25 KYA.Meanwhile,our results showed that the most recent divergence event between Chinese wild and domesticated pigs occurred in the Hetao Plain,northern China,approximately 20 KYA,supporting the possibly independent domestication in northern China along the middle Yellow River.We also found that the maximum effective population size of pigs was~6 times larger than estimated before.An archaic migration from other Sus species originating~2 MYA to European pigs was detected during western colonization of pigs,which may affect the accuracy of previous demographic inference.Our de novo mutation rate estimation and its consequences for demographic history inference reasonably provide a new vision regarding the evolutionary history of pigs.
文摘The World Health Organization has declared the present Zika virus epidemic to be a 'Public Health Emergency of International Concern'. The virus appears to have spread from Thailand to French Polynesia in 2013, and has since infected over a million people in the countries of South and Central America. In most cases the infection is mild and transient, but the virus does appear to be strongly neurotropic and the presumptive cause of both birth defects in fetuses and Guillain-Barr6 syndrome in some adults. In this paper, the techniques and utilities developed in the study of mitochondrial DNA were applied to the Zika virus. As a result, it is possible to show in a simple manner how a phylogenetic tree may be constructed and how the mutation rate of the virus can be measured. The study showed the mutation rate to vary between 12 and 25 bases a year, in a viral genome of 10 272 bases. This rapid mutation rate will enable the geographic spread of the epidemic to be monitored easily and may also prove useful in assisting the identification of preventative measures that are working, and those that are not.
基金the National Natural Science Foundation of China(Grant No.31270107)the National Basic Research Program of China(973 Program)(No.2011CBA00800)+1 种基金the National High Technology Research and Development Program(863 Program)(No.2011AA02A208)the Knowledge Innovation Program of the Chinese Acad-emy of Sciences(No.KSCX2-EW-Q-14).
文摘Development of controllable hypermutable cells can greatly benefit understanding and harnessing microbial evolution.However,there have not been any similar sys-tems developed for Clostridium,an important bacterial genus.Here we report a novel two-step strategy for de-veloping controllable hypermutable cells of Clostridium acetobutylicum,an important and representative indus-trial strain.Firstly,the mutS/L operon essential for methyl-directed mismatch repair(MMR)activity was inactivated from the genome of C.acetobutylicum to generate hy-permutable cells with over 250-fold increased mutation rates.Secondly,a proofreading control system carrying an inducibly expressed mutS/L operon was constructed.The hypermutable cells and the proofreading control system were integrated to form a controllable hypermut-able system SMBMutC,of which the mutation rates can be regulated by the concentration of anhydrotetracycline(aTc).Duplication of the miniPthl-tetR module of the proof-reading control system further signifi cantly expanded the regulatory space of the mutation rates,demonstrating hypermutable Clostridium cells with controllable mutation rates are generated.The developed C.acetobutylicum strain SMBMutC2 showed higher survival capacities than the control strain facing butanol-stress,indicating greatly increased evolvability and adaptability of the controllable hypermutable cells under environmental challenges.