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R M Zhang

Publications and source records attributed to R M Zhang.

8 recordsLinked to original sources
PubMed2006

Genetic dissection of ethanol tolerance in the budding yeast Saccharomyces cerevisiae.

Uncovering genetic control of variation in ethanol tolerance in natural populations of yeast Saccharomyces cerevisiae is essential for understanding the evolution of fermentation, the dominant lifestyle of the species, and for improving efficiency of selection for strains with high ethanol tolerance, a character of great economic value for the brewing and biofuel industries. To date, as many as 251 genes have been predicted to be involved in influencing this character. Candidacy of these genes was determined from a tested phenotypic effect following gene knockout, from an induced change in gene function under an ethanol stress condition, or by mutagenesis. This article represents the first genomics approach for dissecting genetic variation in ethanol tolerance between two yeast strains with a highly divergent trait phenotype. We developed a simple but reliable experimental protocol for scoring the phenotype and a set of STR/SNP markers evenly covering the whole genome. We created a mapping population comprising 319 segregants from crossing the parental strains. On the basis of the data sets, we find that the tolerance trait has a high heritability and that additive genetic variance dominates genetic variation of the trait. Segregation at five QTL detected has explained approximately 50% of phenotypic variation; in particular, the major QTL mapped on yeast chromosome 9 has accounted for a quarter of the phenotypic variation. We integrated the QTL analysis with the predicted candidacy of ethanol resistance genes and found that only a few of these candidates fall in the QTL regions.

Chromosome Mapping↗
PubMed2006

Constructing genetic linkage maps under a tetrasomic model.

An international consortium has launched the whole-genome sequencing of potato, the fourth most important food crop in the world. Construction of genetic linkage maps is an inevitable step for taking advantage of the genome projects for the development of novel cultivars in the autotetraploid crop species. However, linkage analysis in autopolyploids, the kernel of linkage map construction, is theoretically challenging and methodologically unavailable in the current literature. We present here a theoretical analysis and a statistical method for tetrasomic linkage analysis with dominant and/or codominant molecular markers. The analysis reveals some essential properties of the tetrasomic model. The method accounts properly for double reduction and incomplete information of marker phenotype in regard to the corresponding phenotype in estimating the coefficients of double reduction and recombination frequency and in testing their significance by using the marker phenotype data. Computer simulation was developed to validate the analysis and the method and a case study with 201 AFLP and SSR markers scored on 228 full-sib individuals of autotetraploid potato is used to illustrate the utility of the method in map construction in autotetraploid species.

Chromosome Mapping↗
PubMed2005

Modeling population genetic data in autotetraploid species.

Allozyme and PCR-based molecular markers have been widely used to investigate genetic diversity and population genetic structure in autotetraploid species. However, an empirical but inaccurate approach was often used to infer marker genotype from the pattern and intensity of gel bands. Obviously, this introduces serious errors in prediction of the marker genotypes and severely biases the data analysis. This article developed a theoretical model to characterize genetic segregation of alleles at genetic marker loci in autotetraploid populations and a novel likelihood-based method to estimate the model parameters. The model properly accounts for segregation complexities due to multiple alleles and double reduction at autotetrasomic loci in natural populations, and the method takes appropriate account of incomplete marker phenotype information with respect to genotype due to multiple-dosage allele segregation at marker loci in tetraploids. The theoretical analyses were validated by making use of a computer simulation study and their utility is demonstrated by analyzing microsatellite marker data collected from two populations of sycamore maple (Acer pseudoplatanus L.), an economically important autotetraploid tree species. Numerical analyses based on simulation data indicate that the model parameters can be adequately estimated and double reduction is detected with good power using reasonable sample size.

Alleles↗
PubMed2004

Theoretical basis for genetic linkage analysis in autotetraploid species.

Linkage analysis in autotetraploid species has been an historical challenge in quantitative genetics theory and is a stumbling block that urgently needs to be removed in the rapidly emerging genome research on this species, such as cultivated potato. This article presents theory of a full model of tetrasomic linkage and develops a statistical framework for the linkage analysis. The model considers both double reduction and recombination, the most essential features of tetrasomic inheritance with linked loci, whereas the statistical method takes appropriate account of the major complexities in analyzing both dominant and codominant molecular marker data during map reconstruction in tetraploid species. These complexities include the problems arising from multiple dosage of allelic inheritance, the null allele, allelic segregation distortion, mixed bivalent and quadrivalent pairing in meiosis, and incomplete information of marker phenotype data. The theoretical analysis established the relationship between the coefficients of double reduction at linked loci, which is essential in the present tetrasomic linkage analysis and in assessing the impact of double reduction on the evolution of tetraploid populations. The statistical method, based on the combination of theoretical analysis and a computer-based algorithm, provided analytical tools for predicting the maximum-likelihood estimates of the model parameters. A simulation study showed the feasibility of a practical implementation of the method, detailed the procedure of the analysis, validated the power and reliability in the parameter estimation, and compared the present method with those proposed in the current literature.

Computer Simulation↗
PubMed1991

Factors governing selective formation of specific disulfides in synthetic variants of alpha-conotoxin.

alpha-Conotoxin GI is a snail toxin protein consisting of 13 amino acids cross-linked by 2 intramolecular disulfide bridges. This toxin is an antagonist of acetylcholine receptors. The native sequence has been synthesized, along with nine additional variants in which non-cysteine residues are replaced by alanine or the cysteine positions are altered. Each reduced peptide has been oxidized by reaction with oxygen or glutathione both in a folding buffer and in 6 M guanidine hydrochloride. Purified products of oxidation have been characterized with respect to molecular weights and the positions of disulfides. The four cysteines in conotoxin can form two intramolecular disulfides in three different combinations. Relative yields of each of the three isomers have been determined, thereby permitting evaluation of the roles of non-cysteine residues and cysteine placements in the folding of conotoxin. Cysteine positions dominate factors directing formation of the nativelike isomer in a manner that may be predicted from equilibrium constants for loop formation in model peptides containing two cysteines. Alanine substitutions at several positions which are conserved in naturally occurring conotoxins affect the discrimination between the two most favored disulfide arrangements. Substitutions at three nonconserved positions have no structural effect on isomer yields. It therefore is possible to vary these latter three positions in a manner which might help to generate a functional binding surface which is complementary to receptors in the specific prey of a particular species of snail, without affecting the toxin's folding.

Amino Acid Sequence↗
PubMed1989

Dependence of formation of small disulfide loops in two-cysteine peptides on the number and types of intervening amino acids.

Microscopic disulfide-exchange rate constants have been measured for the formation and opening of small disulfide loops in reactions between glutathione and peptides containing 2 cysteines. Twelve cysteine-Xm-cysteine peptides have been studied, where X is an amino acid and m is the number of amino acids between the cysteines. Homopolymers of alanine for m equaling 0-5 are evaluated, as well as X1 and X2 series employing glycine, valine, or proline. Equilibrium constants Kc for loop closing are only slightly dependent on the nature of X. Loops with even values of m generally are favored relative to loops with odd values. Kc increases in the rank order X1, X3, X0, X5, X4, and X2. Formation of a disulfide between sequentially adjacent cysteines therefore is not especially difficult. The dependence of Kc on the odd-even nature of m is compared with similar patterns observed both in statistics of disulfide formation in naturally occurring proteins and in theoretical studies of peptide cyclization. The relative equilibrium populations of intramolecular disulfides in peptides containing cysteine-cysteine-cysteine and cysteine-serine-cysteine-serine-cysteine clusters are consistent with predictions based on the values of Kc in the two-cysteine peptides.

Amino Acid Sequence↗