Multiple comparisons among genomes can clarify their evolution, speciation, and functional innova- tions. To date, the genome sequences of eight grasses representing the most economically important Poaceae (grass) c...Multiple comparisons among genomes can clarify their evolution, speciation, and functional innova- tions. To date, the genome sequences of eight grasses representing the most economically important Poaceae (grass) clades have been published, and their genomic-level comparison is an essential foundation for evolutionary, functional, and translational research. Using a formal and conservative approach, we aligned these genomes. Direct comparison of paralogous gene pairs all duplicated simultaneously reveal striking variation in evolutionary rates among whole genomes, with nucleotide substitution slowest in rice and up to 48% faster in other grasses, adding a new dimension to the value of rice as a grass model. We reconstructed ancestral genome contents for major evolutionary nodes, potentially contributing to understanding the divergence and speciation of grasses. Recent fossil evidence suggests revisions of the estimated dates of key evolutionary events, implying that the pan-grass polyploidization occurred ~96 million years ago and could not be related to the Creta- ceous-Tertiary mass extinction as previously inferred. Adjusted dating to reflect both updated fossil evidence and lineage-specific evolutionary rates suggested that maize subgenome divergence and maize-sorghum divergence were virtually simultaneous, a coincidence that would be explained if poly- ploidization directly contributed to speciation. This work lays a solid foundation for Poaceae transla- tional genomics.展开更多
DNA markers play important roles in plant breed- ing and genetics. The Insertion/Deletion (InDel) marker is one kind of co-dominant DNA markers widely used due to its low cost and high precision. However, the canoni...DNA markers play important roles in plant breed- ing and genetics. The Insertion/Deletion (InDel) marker is one kind of co-dominant DNA markers widely used due to its low cost and high precision. However, the canonical way of searching for InDel markers is time-consuming and labor- intensive. We developed an end-to-end computational solution (InDel Markers Development Platform, IMDP) to identify genome-wide InDel markers under a graphic pipeline environment. IMDP constitutes assembled genome sequen- ces alignment pipeline (AGA-pipe) and next-generation re- sequencing data mapping pipeline (NGS-pipe). With AGA-pipe we are able to identify 12,944 markers between the genome of rice cultivars Nipponbare and 93-11. Using NGS-pipe, we reported 34,794 InDels from re-sequencing data of rice cultivars Wu-Yun-Geng7 and Guang-Lu-Ai4. Combining AGA- pipe and NGS-pipe, we developed 2o5,659 InDels in eight japonica and nine indica cultivars and 2,681 InDels showed a subgroup-specific pattern. Polymerase chain reaction (PCR) analysis of subgroup-specific markers indicated that the precision reached 90% (86 of 95). Finally, to make them available to the public, we have integrated the InDels/markers information into a website (Rice InDel Marker Database, RIMD, http:I/2o2.12o.45.71/). The application of IMDP in rice will facilitate efficiency for development of genome-wide InDel markers, in addition it can be used in other species with reference genome sequences and NGS data.展开更多
Published genomes frequently contain erroneous gene models that represent issues associated with identification of open reading frames,start sites,splice sites,and related structural features.The source of these incon...Published genomes frequently contain erroneous gene models that represent issues associated with identification of open reading frames,start sites,splice sites,and related structural features.The source of these inconsistencies is often traced back to integration across text file formats designed to describe long read alignments and predicted gene structures.In addition,the majority of gene prediction frameworks do not provide robust downstream filtering to remove problematic gene annotations,nor do they represent these annotations in a format consistent with current file standards.These frameworks also lack consideration for functional attributes,such as the presence or absence of protein domains that can be used for gene model validation.To provide oversight to the increasing number of published genome annotations,we present a software package,the Gene Filtering,Analysis,and Conversion(gFACs),to filter,analyze,and convert predicted gene models and alignments.The software operates across a wide range of alignment,analysis,and gene prediction files with a flexible framework for defining gene models with reliable structural and functional attributes.gFACs supports common downstream applications,including genome browsers,and generates extensive details on the filtering process,including distributions that can be visualized to further assess the proposed gene space.gFACs is freely available and implemented in Perl with support from BioPerl libraries at https://gitlab.com/PlantGenomicsLab/gFACs.展开更多
Background:Metronidazole is one of the first-line drugs of choice in the standard triple therapy used to eradicate Helicobacter pylori infection.Hence,the global emergence of metronidazole resistance in Hp poses a maj...Background:Metronidazole is one of the first-line drugs of choice in the standard triple therapy used to eradicate Helicobacter pylori infection.Hence,the global emergence of metronidazole resistance in Hp poses a major challenge to health professionals.Inactivation of RdxA is known to be a major mechanism of conferring metronidazole resistance in H.pylori.However,metronidazole resistance can also arise in H.pylori strains expressing functional RdxA protein,suggesting that there are other mechanisms that may confer resistance to this drug.Methods:We performed whole-genome sequencing on 121 H.pylori clinical strains,among which 73 were metronidazoleresistant.Sequence-alignment analysis of core protein clusters derived from clinical strains containing full-length RdxA was performed.Variable sites in each alignment were statistically compared between the resistant and susceptible groups to determine candidate genes along with their respective amino-acid changes that may account for the development of metronidazole resistance in H.pylori.Results:Resistance due to RdxA truncation was identified in 34%of metronidazole-resistant strains.Analysis of core protein clusters derived from the remaining 48 metronidazole-resistant strains and 48 metronidazole-susceptible identified four variable sites significantly associated with metronidazole resistance.These sites included R16H/C in RdxA,D85N in the inner-membrane protein RclC(HP0565),V265I in a biotin carboxylase protein(HP0370)and A51V/T in a putative threonylcarbamoyl–AMP synthase(HP0918).Conclusions:Our approach identified new potential mechanisms for metronidazole resistance in H.pylori that merit further investigation.展开更多
文摘Multiple comparisons among genomes can clarify their evolution, speciation, and functional innova- tions. To date, the genome sequences of eight grasses representing the most economically important Poaceae (grass) clades have been published, and their genomic-level comparison is an essential foundation for evolutionary, functional, and translational research. Using a formal and conservative approach, we aligned these genomes. Direct comparison of paralogous gene pairs all duplicated simultaneously reveal striking variation in evolutionary rates among whole genomes, with nucleotide substitution slowest in rice and up to 48% faster in other grasses, adding a new dimension to the value of rice as a grass model. We reconstructed ancestral genome contents for major evolutionary nodes, potentially contributing to understanding the divergence and speciation of grasses. Recent fossil evidence suggests revisions of the estimated dates of key evolutionary events, implying that the pan-grass polyploidization occurred ~96 million years ago and could not be related to the Creta- ceous-Tertiary mass extinction as previously inferred. Adjusted dating to reflect both updated fossil evidence and lineage-specific evolutionary rates suggested that maize subgenome divergence and maize-sorghum divergence were virtually simultaneous, a coincidence that would be explained if poly- ploidization directly contributed to speciation. This work lays a solid foundation for Poaceae transla- tional genomics.
基金supported by the Funds from National Natural Science Foundation of China(31270222,31470397 and 31230051)Key Project on Basic Research from Science and Technology Commission of Shanghai(14JC1403900)+5 种基金Project on Breeding from Agriculture Commission of Shanghai(2013-13)the China Innovative Research Team,Ministry of Education,Chinathe 111 Project (B14016)the Innovation Program of Shanghai Municipal Education Commission(13ZZ018)the Innovation Program of Shanghai Pudong Science and Technology Commission (PKJ2013-N03)National Transgenic Major Program Grants 2014ZX08009-003-003
文摘DNA markers play important roles in plant breed- ing and genetics. The Insertion/Deletion (InDel) marker is one kind of co-dominant DNA markers widely used due to its low cost and high precision. However, the canonical way of searching for InDel markers is time-consuming and labor- intensive. We developed an end-to-end computational solution (InDel Markers Development Platform, IMDP) to identify genome-wide InDel markers under a graphic pipeline environment. IMDP constitutes assembled genome sequen- ces alignment pipeline (AGA-pipe) and next-generation re- sequencing data mapping pipeline (NGS-pipe). With AGA-pipe we are able to identify 12,944 markers between the genome of rice cultivars Nipponbare and 93-11. Using NGS-pipe, we reported 34,794 InDels from re-sequencing data of rice cultivars Wu-Yun-Geng7 and Guang-Lu-Ai4. Combining AGA- pipe and NGS-pipe, we developed 2o5,659 InDels in eight japonica and nine indica cultivars and 2,681 InDels showed a subgroup-specific pattern. Polymerase chain reaction (PCR) analysis of subgroup-specific markers indicated that the precision reached 90% (86 of 95). Finally, to make them available to the public, we have integrated the InDels/markers information into a website (Rice InDel Marker Database, RIMD, http:I/2o2.12o.45.71/). The application of IMDP in rice will facilitate efficiency for development of genome-wide InDel markers, in addition it can be used in other species with reference genome sequences and NGS data.
基金supported by the National Science Foundation Plant Genome Research Program of the United States(Grant No.1444573)
文摘Published genomes frequently contain erroneous gene models that represent issues associated with identification of open reading frames,start sites,splice sites,and related structural features.The source of these inconsistencies is often traced back to integration across text file formats designed to describe long read alignments and predicted gene structures.In addition,the majority of gene prediction frameworks do not provide robust downstream filtering to remove problematic gene annotations,nor do they represent these annotations in a format consistent with current file standards.These frameworks also lack consideration for functional attributes,such as the presence or absence of protein domains that can be used for gene model validation.To provide oversight to the increasing number of published genome annotations,we present a software package,the Gene Filtering,Analysis,and Conversion(gFACs),to filter,analyze,and convert predicted gene models and alignments.The software operates across a wide range of alignment,analysis,and gene prediction files with a flexible framework for defining gene models with reliable structural and functional attributes.gFACs supports common downstream applications,including genome browsers,and generates extensive details on the filtering process,including distributions that can be visualized to further assess the proposed gene space.gFACs is freely available and implemented in Perl with support from BioPerl libraries at https://gitlab.com/PlantGenomicsLab/gFACs.
基金This project was supported by ShenZhen’s Sanming Project(Grant No:SZSM201510050)University of Malaya-Ministry of Education(UM-MoE)High Impact Research(HIR)grant(reference UM.C/625/1/HIR/MoE/CHAN13/3,Account No.H-50001-A000030)a National Health and Medical Research Council(NHMRC)Sir McFarlane Burnett Fellowship grant(572723)to B.J.M.,the Vice Chancellor of the University of Western Australia,and the Western Australian Department of Commerce and Department of Health.A.W.D.was supported by an Early Career Research Fellowship from the NHMRC(APP1073250).
文摘Background:Metronidazole is one of the first-line drugs of choice in the standard triple therapy used to eradicate Helicobacter pylori infection.Hence,the global emergence of metronidazole resistance in Hp poses a major challenge to health professionals.Inactivation of RdxA is known to be a major mechanism of conferring metronidazole resistance in H.pylori.However,metronidazole resistance can also arise in H.pylori strains expressing functional RdxA protein,suggesting that there are other mechanisms that may confer resistance to this drug.Methods:We performed whole-genome sequencing on 121 H.pylori clinical strains,among which 73 were metronidazoleresistant.Sequence-alignment analysis of core protein clusters derived from clinical strains containing full-length RdxA was performed.Variable sites in each alignment were statistically compared between the resistant and susceptible groups to determine candidate genes along with their respective amino-acid changes that may account for the development of metronidazole resistance in H.pylori.Results:Resistance due to RdxA truncation was identified in 34%of metronidazole-resistant strains.Analysis of core protein clusters derived from the remaining 48 metronidazole-resistant strains and 48 metronidazole-susceptible identified four variable sites significantly associated with metronidazole resistance.These sites included R16H/C in RdxA,D85N in the inner-membrane protein RclC(HP0565),V265I in a biotin carboxylase protein(HP0370)and A51V/T in a putative threonylcarbamoyl–AMP synthase(HP0918).Conclusions:Our approach identified new potential mechanisms for metronidazole resistance in H.pylori that merit further investigation.