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Lihua Xiao - One of the best experts on this subject based on the ideXlab platform.
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comparative genomic analysis reveals occurrence of Genetic Recombination in virulent cryptosporidium hominis subtypes and telomeric gene duplications in cryptosporidium parvum
BMC Genomics, 2015Co-Authors: Yaoyu Feng, Yaqiong Guo, Kevin Tang, Lori A Rowe, Dawn M Roellig, Kristine Knipe, Michael Frace, Chunfu Yang, Lihua XiaoAbstract:Cryptosporidium hominis is a dominant species for human cryptosporidiosis. Within the species, IbA10G2 is the most virulent subtype responsible for all C. hominis–associated outbreaks in Europe and Australia, and is a dominant outbreak subtype in the United States. In recent yearsIaA28R4 is becoming a major new subtype in the United States. In this study, we sequenced the genomes of two field specimens from each of the two subtypes and conducted a comparative genomic analysis of the obtained sequences with those from the only fully sequenced Cryptosporidium parvum genome. Altogether, 8.59-9.05 Mb of Cryptosporidium sequences in 45–767 assembled contigs were obtained from the four specimens, representing 94.36-99.47% coverage of the expected genome. These genomes had complete synteny in gene organization and 96.86-97.0% and 99.72-99.83% nucleotide sequence similarities to the published genomes of C. parvum and C. hominis, respectively. Several major insertions and deletions were seen between C. hominis and C. parvum genomes, involving mostly members of multicopy gene families near telomeres. The four C. hominis genomes were highly similar to each other and divergent from the reference IaA25R3 genome in some highly polymorphic regions. Major sequence differences among the four specimens sequenced in this study were in the 5′ and 3′ ends of chromosome 6 and the gp60 region, largely the result of Genetic Recombination. The sequence similarity among specimens of the two dominant outbreak subtypes and Genetic Recombination in chromosome 6, especially around the putative virulence determinant gp60 region, suggest that Genetic Recombination plays a potential role in the emergence of hyper-transmissible C. hominis subtypes. The high sequence conservation between C. parvum and C. hominis genomes and significant differences in copy numbers of MEDLE family secreted proteins and insulinase-like proteases indicate that telomeric gene duplications could potentially contribute to host expansion in C. parvum.
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population Genetic characterisation of dominant cryptosporidium parvum subtype iiaa15g2r1
International Journal for Parasitology, 2013Co-Authors: Yaoyu Feng, Eucaris Torres, Lin Wang, Dwight D Bowman, Lihua XiaoAbstract:The subtype IIaA15G2R1 at the 60 kDa glycoprotein (gp60) gene locus is the most dominant Cryptosporidium parvum infecting dairy cattle and humans in industrialised nations. The reasons for its high transmissibility are not clear, and it remains to be determined whether this subtype represents a homogeneous parasite population. In this study, we sequence-characterised 26 IIaA15G2R subtype specimens and 26 non-IIaA15G2R subtype specimens from the United States, Canada, United Kingdom and Spain at seven other known polymorphic loci, including CP47, CP56, DZ-HRGP, MSC6-5, MSC6-7, RPGR and ZPT. Extensive heterogeneity within IIaA15G2R1 and discordance in typing results between gp60 and other Genetic markers were observed. Results of inter-locus and intra-ZPT linkage disequilibrium and Recombination analyses indicated that the heterogeneity within IIaA15G2R1 and discordance in typing results among Genetic loci were largely due to the occurrence of Genetic Recombination, mostly within the gp60 subtype IIaA15G2R1. Although there was no clear population diversion between IIaA15G2R and non-IIaA15G2R subtypes, results of STRUCTURE and FST analyses suggested the presence of at least two subpopulations; subpopulation 1 had an epidemic population structure and was widely distributed, whereas subpopulation 2 had a clonal population structure and consisted of geographically segregated multilocus subtypes. Genetic Recombination between epidemic and geographically segregated C. parvum populations appeared to be a driving force in the emergence of a hyper-transmissible IIaA15G2R1 subtype. Genetic Recombination was observed even between the zoonotic IIa subtype family and anthroponotic subtype family IIc at CP56, MSC6-7 and ZPT. Thus, the IIaA15G2R1 subtype at gp60 is likely a fitness marker for C. parvum and the wide spread of IIaA15G2R1 subtype around the world is probably independent of the sequence characteristics at other Genetic loci.
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Genetic Recombination and cryptosporidium hominis virulent subtype iba10g2
Emerging Infectious Diseases, 2013Co-Authors: Lihua Xiao, Vitaliano Cama, Ynes R Ortega, Robert H Gilman, Meijin Guo, Yaoyu FengAbstract:Little is known about the emergence and spread of virulent subtypes of Cryptosporidium hominis, the predominant species responsible for human cryptosporidiosis. We conducted sequence analyses of 32 Genetic loci of 53 C. hominis specimens isolated from a longitudinally followed cohort of children living in a small community. We identified by linkage disequilibrium and Recombination analyses only limited Genetic Recombination, which occurred exclusively within the 60-kDa glycoprotein gene subtype IbA10G2, a predominant subtype for outbreaks in industrialized nations and a virulent subtype in the study community. Intensive transmission of virulent subtype IbA10G2 in the study area might have resulted in Genetic Recombination with other subtypes. Moreover, we identified selection for IbA10G2 at a 129-kb region around the 60-kDa glycoprotein gene in chromosome 6. These findings improve our understanding of the origin and evolution of C. hominis subtypes and the spread of virulent subtypes.
Stephen C Kowalczykowski - One of the best experts on this subject based on the ideXlab platform.
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initiation of Genetic Recombination and Recombination dependent replication
Trends in Biochemical Sciences, 2000Co-Authors: Stephen C KowalczykowskiAbstract:Recombination initiates at double-stranded DNA breaks and at single-stranded DNA gaps. These DNA strand discontinuities can arise from DNA-damaging agents and from normal DNA replication when the DNA polymerase encounters an imperfection in the DNA template or another protein. The machinery of homologous Recombination acts at these breaks and gaps to promote the events that result in gene Recombination, as well as the reattachment of detached replication arms and the resumption of DNA replication. In Escherichia coli, these events require collaboration (RecA, RecBCD, RecFOR, RecQ, RuvABC and SSB proteins) and DNA replication (PriABC proteins and the DNA polymerases). The initial steps common to these Recombination and Recombination-dependent replication processes are reviewed.
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interaction of escherichia coli reca protein with lexa repressor i lexa repressor cleavage is competitive with binding of a secondary dna molecule
Journal of Biological Chemistry, 1996Co-Authors: William M Rehrauer, Polly E Lavery, Elise L Palmer, Ravee N Singh, Stephen C KowalczykowskiAbstract:Abstract Essential to the two distinct cellular events of Genetic Recombination and SOS induction in Escherichia coli, RecA protein promotes the homologous pairing and exchange of DNA strands and the proteolytic cleavage of the LexA repressor, respectively. Since both of these activities require single-stranded DNA (ssDNA) and ATP, the inter-relationship between these reactions was investigated and found to display many parallels. The extent of active complex formed between RecA protein and M13 ssDNA, as measured by both ATP hydrolysis and LexA proteolysis, is stimulated in a similar manner by either a reduction in magnesium ion concentration or the presence of single-stranded DNA binding (SSB) protein. However, unexpectedly, SSB protein inhibits both LexA proteolysis and ATP hydrolysis (in assays containing repressor) at concentrations of RecA protein that are substoichiometric to the ssDNA, arguing that LexA repressor affects the competition between RecA and SSB proteins for limited ssDNA binding sites. Additionally, attenuation of LexA repressor cleavage in the presence of double-stranded DNA or by an excess of ssDNA suggests that interaction of the RecA nucleoprotein filament with either LexA repressor or a secondary DNA molecule is mutually exclusive. The significance of these results is discussed in the context of both the regulation of inducible responses to DNA damage, and the competitive relationship between the processes of SOS induction and Genetic Recombination.
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interaction of escherichia coli reca protein with lexa repressor
1996Co-Authors: I Lexa, William M Rehrauer, Polly E Lavery, Elise L Palmer, Ravee N Singhi, Stephen C KowalczykowskiAbstract:Essential to the two distinct cellular events of Genetic Recombination and SOS induction in Escherichia coli, RecA protein promotes the homologous pairing and exchange of DNA strands and the proteolytic cleavage of the LexA repressor, respectively. Since both of these activities require single-stranded DNA (ssDNA) and ATP, the inter-relationship between these reactions was investigated and found to display many parallels. The extent of active complex formed between RecA protein and M13 ssDNA, as measured by both ATP hydrolysis and LexA proteolysis, is stimulated in a similar manner by either a reduction in magnesium ion concentration or the presence of single-stranded DNA binding (SSB) protein. However, unexpectedly, SSB protein inhibits both LexA proteolysis and ATP hydrolysis (in assays containing repressor) at concentrations of RecA protein that are substoichiometric to the ssDNA, arguing that LexA repressor affects the competition between RecA and SSB proteins for limited ssDNA binding sites. Additionally, attenuation of LexA repressor cleavage in the presence of double-stranded DNA or by an excess of ssDNA suggests that interaction of the RecA nucleoprotein filament with either LexA repressor or a secondary DNA molecule is mutually exclusive. The significance of these results is discussed in the context of both the regulation of inducible responses to DNA damage, and the competitive relationship between the processes of SOS induction and Genetic Recombination.
Yaoyu Feng - One of the best experts on this subject based on the ideXlab platform.
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comparative genomic analysis reveals occurrence of Genetic Recombination in virulent cryptosporidium hominis subtypes and telomeric gene duplications in cryptosporidium parvum
BMC Genomics, 2015Co-Authors: Yaoyu Feng, Yaqiong Guo, Kevin Tang, Lori A Rowe, Dawn M Roellig, Kristine Knipe, Michael Frace, Chunfu Yang, Lihua XiaoAbstract:Cryptosporidium hominis is a dominant species for human cryptosporidiosis. Within the species, IbA10G2 is the most virulent subtype responsible for all C. hominis–associated outbreaks in Europe and Australia, and is a dominant outbreak subtype in the United States. In recent yearsIaA28R4 is becoming a major new subtype in the United States. In this study, we sequenced the genomes of two field specimens from each of the two subtypes and conducted a comparative genomic analysis of the obtained sequences with those from the only fully sequenced Cryptosporidium parvum genome. Altogether, 8.59-9.05 Mb of Cryptosporidium sequences in 45–767 assembled contigs were obtained from the four specimens, representing 94.36-99.47% coverage of the expected genome. These genomes had complete synteny in gene organization and 96.86-97.0% and 99.72-99.83% nucleotide sequence similarities to the published genomes of C. parvum and C. hominis, respectively. Several major insertions and deletions were seen between C. hominis and C. parvum genomes, involving mostly members of multicopy gene families near telomeres. The four C. hominis genomes were highly similar to each other and divergent from the reference IaA25R3 genome in some highly polymorphic regions. Major sequence differences among the four specimens sequenced in this study were in the 5′ and 3′ ends of chromosome 6 and the gp60 region, largely the result of Genetic Recombination. The sequence similarity among specimens of the two dominant outbreak subtypes and Genetic Recombination in chromosome 6, especially around the putative virulence determinant gp60 region, suggest that Genetic Recombination plays a potential role in the emergence of hyper-transmissible C. hominis subtypes. The high sequence conservation between C. parvum and C. hominis genomes and significant differences in copy numbers of MEDLE family secreted proteins and insulinase-like proteases indicate that telomeric gene duplications could potentially contribute to host expansion in C. parvum.
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population Genetic characterisation of dominant cryptosporidium parvum subtype iiaa15g2r1
International Journal for Parasitology, 2013Co-Authors: Yaoyu Feng, Eucaris Torres, Lin Wang, Dwight D Bowman, Lihua XiaoAbstract:The subtype IIaA15G2R1 at the 60 kDa glycoprotein (gp60) gene locus is the most dominant Cryptosporidium parvum infecting dairy cattle and humans in industrialised nations. The reasons for its high transmissibility are not clear, and it remains to be determined whether this subtype represents a homogeneous parasite population. In this study, we sequence-characterised 26 IIaA15G2R subtype specimens and 26 non-IIaA15G2R subtype specimens from the United States, Canada, United Kingdom and Spain at seven other known polymorphic loci, including CP47, CP56, DZ-HRGP, MSC6-5, MSC6-7, RPGR and ZPT. Extensive heterogeneity within IIaA15G2R1 and discordance in typing results between gp60 and other Genetic markers were observed. Results of inter-locus and intra-ZPT linkage disequilibrium and Recombination analyses indicated that the heterogeneity within IIaA15G2R1 and discordance in typing results among Genetic loci were largely due to the occurrence of Genetic Recombination, mostly within the gp60 subtype IIaA15G2R1. Although there was no clear population diversion between IIaA15G2R and non-IIaA15G2R subtypes, results of STRUCTURE and FST analyses suggested the presence of at least two subpopulations; subpopulation 1 had an epidemic population structure and was widely distributed, whereas subpopulation 2 had a clonal population structure and consisted of geographically segregated multilocus subtypes. Genetic Recombination between epidemic and geographically segregated C. parvum populations appeared to be a driving force in the emergence of a hyper-transmissible IIaA15G2R1 subtype. Genetic Recombination was observed even between the zoonotic IIa subtype family and anthroponotic subtype family IIc at CP56, MSC6-7 and ZPT. Thus, the IIaA15G2R1 subtype at gp60 is likely a fitness marker for C. parvum and the wide spread of IIaA15G2R1 subtype around the world is probably independent of the sequence characteristics at other Genetic loci.
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Genetic Recombination and cryptosporidium hominis virulent subtype iba10g2
Emerging Infectious Diseases, 2013Co-Authors: Lihua Xiao, Vitaliano Cama, Ynes R Ortega, Robert H Gilman, Meijin Guo, Yaoyu FengAbstract:Little is known about the emergence and spread of virulent subtypes of Cryptosporidium hominis, the predominant species responsible for human cryptosporidiosis. We conducted sequence analyses of 32 Genetic loci of 53 C. hominis specimens isolated from a longitudinally followed cohort of children living in a small community. We identified by linkage disequilibrium and Recombination analyses only limited Genetic Recombination, which occurred exclusively within the 60-kDa glycoprotein gene subtype IbA10G2, a predominant subtype for outbreaks in industrialized nations and a virulent subtype in the study community. Intensive transmission of virulent subtype IbA10G2 in the study area might have resulted in Genetic Recombination with other subtypes. Moreover, we identified selection for IbA10G2 at a 129-kb region around the 60-kDa glycoprotein gene in chromosome 6. These findings improve our understanding of the origin and evolution of C. hominis subtypes and the spread of virulent subtypes.
Richard J. Bennett - One of the best experts on this subject based on the ideXlab platform.
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The Parasexual Cycle in Candida albicans Provides an Alternative Pathway to Meiosis for the Formation of Recombinant Strains
2013Co-Authors: Anja Forche, Dana Schaefer, Judith Berman, Kevin Alby, Er D. Johnson, Richard J. BennettAbstract:Candida albicans has an elaborate, yet efficient, mating system that promotes conjugation between diploid a and a strains. The product of mating is a tetraploid a/a cell that must undergo a reductional division to return to the diploid state. Despite the presence of several ‘‘meiosis-specific’ ’ genes in the C. albicans genome, a meiotic program has not been observed. Instead, tetraploid products of mating can be induced to undergo efficient, random chromosome loss, often producing strains that are diploid, or close to diploid, in ploidy. Using SNP and comparative genome hybridization arrays we have now analyzed the genotypes of products from the C. albicans parasexual cycle. We show that the parasexual cycle generates progeny strains with shuffled combinations of the eight C. albicans chromosomes. In addition, several isolates had undergone extensive Genetic Recombination between homologous chromosomes, including multiple gene conversion events. Progeny strains exhibited altered colony morphologies on laboratory media, demonstrating that the parasexual cycle generates phenotypic variants of C. albicans. In several fungi, including Saccharomyces cerevisiae and Schizosaccharomyces pombe, the conserved Spo11 protein is integral to meiotic Recombination, where it is required for the formation of DNA double-strand breaks. We show that deletion of SPO11 prevented Genetic Recombination between homologous chromosomes during the C. albicans parasexual cycle. These findings suggest that at least one meiosis-specific gene has been re-programmed to mediate Genetic Recombination during the alternative parasexual life cycle of C. albicans. We discuss, in light of the long association of C. albicans wit
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The parasexual cycle in Candida albicans provides an alternative pathway to meiosis for the formation of recombinant strains
PLoS Biology, 2008Co-Authors: Anja Forche, Dana Schaefer, Judith Berman, Kevin Alby, Alexander D Johnson, Richard J. BennettAbstract:Candida albicans has an elaborate, yet efficient, mating system that promotes conjugation between diploid a and alpha strains. The product of mating is a tetraploid a/alpha cell that must undergo a reductional division to return to the diploid state. Despite the presence of several "meiosis-specific" genes in the C. albicans genome, a meiotic program has not been observed. Instead, tetraploid products of mating can be induced to undergo efficient, random chromosome loss, often producing strains that are diploid, or close to diploid, in ploidy. Using SNP and comparative genome hybridization arrays we have now analyzed the genotypes of products from the C. albicans parasexual cycle. We show that the parasexual cycle generates progeny strains with shuffled combinations of the eight C. albicans chromosomes. In addition, several isolates had undergone extensive Genetic Recombination between homologous chromosomes, including multiple gene conversion events. Progeny strains exhibited altered colony morphologies on laboratory media, demonstrating that the parasexual cycle generates phenotypic variants of C. albicans. In several fungi, including Saccharomyces cerevisiae and Schizosaccharomyces pombe, the conserved Spo11 protein is integral to meiotic Recombination, where it is required for the formation of DNA double-strand breaks. We show that deletion of SPO11 prevented Genetic Recombination between homologous chromosomes during the C. albicans parasexual cycle. These findings suggest that at least one meiosis-specific gene has been re-programmed to mediate Genetic Recombination during the alternative parasexual life cycle of C. albicans. We discuss, in light of the long association of C. albicans with warm-blooded animals, the potential advantages of a parasexual cycle over a conventional sexual cycle.
Galina V Petukhova - One of the best experts on this subject based on the ideXlab platform.
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Extensive sex differences at the initiation of Genetic Recombination
Nature, 2018Co-Authors: Kevin Brick, Fatima Smagulova, R Daniel Camerini-otero, Sarah Thibault-sennett, Kwan-wood G. Lam, Florencia Pratto, Galina V PetukhovaAbstract:Meiotic Recombination differs between males and females; however, when and how these differences are established is unknown. Here we identify extensive sex differences at the initiation of Recombination by mapping hotspots of meiotic DNA double-strand breaks in male and female mice. Contrary to past findings in humans, few hotspots are used uniquely in either sex. Instead, grossly different Recombination landscapes result from up to fifteen-fold differences in hotspot usage between males and females. Indeed, most Recombination occurs at sex-biased hotspots. Sex-biased hotspots seem to be partly determined by chromosome structure, and DNA methylation, which is absent in females at the onset of meiosis, has a substantial role. Sex differences are also evident later in meiosis as the rate at which meiotic breaks are repaired as crossovers differs between males and females in distal regions. The suppression of distal crossovers may help to minimize age-related aneuploidy that arises owing to cohesion loss during dictyate arrest in females.
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extensive sex differences at the initiation of Genetic Recombination
bioRxiv, 2017Co-Authors: Kevin Brick, Fatima Smagulova, Florencia Pratto, Sarah Thibaultsennett, Kwanwood Gabriel Lam, Daniel R Cameriniotero, Galina V PetukhovaAbstract:Homologous Recombination in meiosis is initiated by programmed DNA double strand breaks (DSBs) and DSB repair as a crossover is essential to prevent chromosomal abnormalities in gametes. Sex differences in Recombination have been previously observed by analyses of Recombination end-products. To understand when and how sex differences are established, we built genome-wide maps of meiotic DSBs in both male and female mice. We found that most Recombination initiates at sex-biased DSB hotspots. Local context, the choice of DSB targeting pathway and sex-specific patterns of DNA methylation give rise to these differences. Sex differences are not limited to the initiation stage, as the rate at which DSBs are repaired as crossovers appears to differ between the sexes in distal regions. This uneven repair patterning may be linked to the higher aneuploidy rate in females. Together, these data demonstrate that sex differences occur early in meiotic Recombination.
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Genetic Recombination is directed away from functional genomic elements in mice.
Nature, 2012Co-Authors: Kevin Brick, Fatima Smagulova, Pavel Khil, R Daniel Camerini-otero, Galina V PetukhovaAbstract:Genetic Recombination occurs during meiosis, the key developmental programme of gametogenesis. Recombination in mammals has been recently linked to the activity of a histone H3 methyltransferase, PR domain containing 9 (PRDM9), the product of the only known speciation-associated gene in mammals. PRDM9 is thought to determine the preferred Recombination sites--Recombination hotspots--through sequence-specific binding of its highly polymorphic multi-Zn-finger domain. Nevertheless, Prdm9 knockout mice are proficient at initiating Recombination. Here we map and analyse the genome-wide distribution of Recombination initiation sites in Prdm9 knockout mice and in two mouse strains with different Prdm9 alleles and their F(1) hybrid. We show that PRDM9 determines the positions of practically all hotspots in the mouse genome, with the exception of the pseudo-autosomal region (PAR)--the only area of the genome that undergoes Recombination in 100% of cells. Surprisingly, hotspots are still observed in Prdm9 knockout mice, and as in wild type, these hotspots are found at H3 lysine 4 (H3K4) trimethylation marks. However, in the absence of PRDM9, most Recombination is initiated at promoters and at other sites of PRDM9-independent H3K4 trimethylation. Such sites are rarely targeted in wild-type mice, indicating an unexpected role of the PRDM9 protein in sequestering the Recombination machinery away from gene-promoter regions and other functional genomic elements.