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PubMed1986

Gene differentiation among ten endogamous groups of West Bengal, India.

Ten endogamous populations of West Bengal, India have been surveyed for genetic variation in 12 systems. These populations encompass all social ranks in the caste hierarchy and cover almost the entire geographic area of the state. Gene diversity analysis suggests that these groups exhibit significant allele frequency variation at all but three loci. The overall genetic difference is not, however, in accord with the classification based on caste. Two low-ranking scheduled caste groups are, in fact, in close proximity with the high-caste ones, suggesting evidence of past generations of gene flow among them. Three different clusters of groups emerge from the present data, providing support for the anthropologic assertion that in Bengal Proto-Australoid, Caucasoid, and Mongoloid racial elements generally coexist. However, these three components are not uniformly present in all groups. Geographic separation of the groups is a strong determinant of the gene differentiation that exists among these populations.

Alleles↗

PubMed2007

Interactions between peptides containing nucleobase amino acids and T7 phages displaying S. cerevisiae proteins.

The importance of high-throughput analyses of protein abundances and functions is interestingly increasing in genomic/proteomic studies. In such postgenome sequencing era, a protein-detecting chip, in which a large number of molecules specifically capturing target proteins (capturing agents) such as antibodies, recombinant proteins, and small molecules are arrayed onto solid, wet, or semi-wet substrates, enables comprehensive analysis of proteomes by a single experiment. However, whole proteomes are generally complicated for comprehensive analyses so that alternative approaches to subproteome analysis categorized by protein functions and binding properties (focused proteome) would be effective. Approaching the goal of development of designed peptide chip for protein analysis, diversity increases in peptide structures and validation of target proteins are needed. We herein describe design and synthesis of nucleobase amino acid (NBA)-containing peptides, selection of nucleic acid-related proteins derived from S. cerevisiae, and detection of interactions between NBA-containing peptides and T7 phages displaying proteins by both enzyme-linked immunosorbent assays (ELISA) and label-free anomalous reflection of gold (AR) measurements. Twenty-eight phage clones were obtained by the phage-display method and sequenced. Ten of 28 clones were expected to be nucleic acid-related proteins including initiation factor, TYB protein, ribosomal proteins, elongation factor, ATP synthase subunit, GTP-binding protein, and ribonuclease. Other phage clones encoded several classes of enzymes such as reductase, oxidase, aldolase, metalloprotease, and hexokinase. Both ELISA and AR measurements suggested that the methodology of in vitro selection for recognition of the NBA-containing peptide presented in this study was successfully established. Such a combination of NBA and phage display technologies would be potential to efficiently confirm valuable target proteins binding specifically to capturing agents, to be arrayed onto solid surfaces to develop the designed peptide chip.

Bacteriophage T7↗

PubMed1997

Application of inter simple sequence repeat (ISSR) markers to plant genetics.

Microsatellites or simple sequence repeats (SSRs) are ubiquitous in eukaryotic genomes. Single-locus SSR markers have been developed for a number of species, although there is a major bottleneck in developing SSR markers whereby flanking sequences must be known to design 5'-anchors for polymerase chain reaction (PCR) primers. Inter SSR (ISSR) fingerprinting was developed such that no sequence knowledge was required. Primers based on a repeat sequence, such as (CA)n, can be made with a degenerate 3'-anchor, such as (CA)8RG or (AGC)6TY. The resultant PCR reaction amplifies the sequence between two SSRs, yielding a multilocus marker system useful for fingerprinting, diversity analysis and genome mapping. PCR products are radiolabelled with 32P or 33P via end-labelling or PCR incorporation, and separated on a polyacrylamide sequencing gel prior to autoradiographic visualisation. A typical reaction yields 20-100 bands per lane depending on the species and primer. We have used ISSR fingerprinting in a number of plant species, and report here some results on two important tropical species, sorghum and banana. Previous investigators have demonstrated that ISSR analysis usually detects a higher level of polymorphism than that detected with restriction fragment length polymorphism (RFLP) or random amplified polymorphic DNA (RAPD) analyses. Our data indicate that this is not a result of greater polymorphism genetically, but rather technical reasons related to the detection methodology used for ISSR analysis.

Autoradiography↗

PubMed1996

Gene conversion and homologous recombination in murine B cells.

Gene conversion has been found to be important in the diversification of antibody genes in chickens and in rabbits. In other species, however, it is not clear whether gene conversion plays any role in antibody diversity. Analysis of an H-chain antibody gene construct that was designed to optimize the detection of gene conversion events in transgenic mice has shown that sequence transfers that resemble gene conversion events can occur in murine B cells and are associated with somatic hypermutation. This raises the possibility that an error-prone gene conversion mechanism might play a role in murine somatic hypermutation.

Animals↗

PubMed1978

Is there a pattern of gene differentiation in the Indian populations.

Indian populations divided into a number of endogamous groups consisting of different castes, languages, religions, and tribes provide unique opportunities for examining the extent and nature of genetic differentiation at a microevolutionary stage. The genetic relationships between some of these Indian population groups have been examined using electrophoretic data from several biochemical loci in a gene diversity analysis. Does this type of analysis provide any insight into what causes such gene differentiation? What patterns of genetic variation emerge from these empirical findings? Answers are sought by relating the observed heterozygosity, genetic distance, and allied statistics to a mutation-drift hypothesis. The statistics used are: (1) interlocus mean and variance of heterozygosity, (2) mean and variance of genetic distance, and (3) correlation of heterozygosity and gene identity. The observed relationships between these sets of statistics agree well with the ones predicted by the hypothesis that different alleles at protein loci are selectively equivalent and gene frequency change occurs predominantly due to genetic drift.

Gene Frequency↗

PubMed2002

Structure and level of genetic diversity in various bean types evidenced with microsatellite markers isolated from a genomic enriched library.

We have constructed a common bean genomic library enriched for microsatellite motifs (ATA), (CA), (CAC) and (GA). After screening, 60% of the clones selected from the library enriched for the (ATA) repeat contained microsatellites versus 21% of the clones from the library enriched for (GA) (CA) and (CAC) repeats. Fifteen primer pairs have been developed allowing for the amplification of SSR loci. We have evaluated the genetic diversity of these loci between 45 different bean lines belonging to nine various quality types. A total of 81 alleles were detected at the 15 microsatellite loci with an average of 5.3 alleles per locus. We have investigated the origin of allelic size polymorphism at the locus PvATA20 in which the number of repeats ranges from 24 to 85. We have related these large differences in repeat number to unequal crossing-over between repeated DNA regions. The diversity analysis revealed contrasted levels of variability according to the bean type. The lower level was evidenced for the very fine French bean, showing the effect of breeders intensive selection.

Journal Article↗

PubMed2004

Demonstration of linkage and development of the first low-density genetic map of garlic, based on AFLP markers.

Garlic (Allium sativum L.) is a long-cultivated, clonally propagated diploid plant (2n=2x=16). With routine seed production now underway, we used populations (MP1 and MP2) generated by self-pollination of unrelated plants to generate two low-density genetic maps of garlic, consisting of amplified fragment length polymorphism (AFLP) and gene-specific markers. We did not observe any two plants with identical marker patterns in either population, indicating that they were the result of amphimixis rather than apomixis. This is an important finding, since several Alliums are facultative apomicts. A total of 360 markers segregated in MP1 (12.8 AFLP markers per primer combination) and 321 markers segregated in MP2 (13.9 per primer combination) to indicate a fairly high level of genetic heterozygosity in the garlic nuclear genome. Of these markers, 15.3% in MP1 and 24.3% in MP2 had segregation ratios distorted from the expected 3:1. Interestingly, 94.7% of those distorted segregations fit a 15:1 segregation ratio for duplicated loci, suggesting extensive levels of duplication in the garlic genome and supporting similar observations for onion. The genetic map for the MP1 family with 216 markers spanned 1,166 cM of the garlic genome (5.4 cM average), while 143 markers of MP2 spanned 862 cM (6.0 cM average). Gene-specific markers for alliinase, chitinase, sucrose 1-fructosyltransferase (SST-1), and chalcone synthase (CHS) were mapped, demonstrating the immediate utility of the garlic genetic map. These two garlic families had relatively few segregating AFLP markers in common, which supports their relatively distant relationship based on diversity analysis. Of those markers that were conserved, linkages were also conserved.

Chromosome Mapping↗

PubMed2005

SSR allelic variation in almond (Prunus dulcis Mill.).

Sixteen SSR markers including eight EST-SSR and eight genomic SSRs were used for genetic diversity analysis of 23 Chinese and 15 international almond cultivars. EST- and genomic SSR markers previously reported in species of Prunus, mainly peach, proved to be useful for almond genetic analysis. DNA sequences of 117 alleles of six of the 16 SSR loci were analysed to reveal sequence variation among the 38 almond accessions. For the four SSR loci with AG/CT repeats, no insertions or deletions were observed in the flanking regions of the 98 alleles sequenced. Allelic size variation of these loci resulted exclusively from differences in the structures of repeat motifs, which involved interruptions or occurrences of new motif repeats in addition to varying number of AG/CT repeats. Some alleles had a high number of uninterrupted repeat motifs, indicating that SSR mutational patterns differ among alleles at a given SSR locus within the almond species. Allelic homoplasy was observed in the SSR loci because of base substitutions, interruptions or compound repeat motifs. Substitutions in the repeat regions were found at two SSR loci, suggesting that point mutations operate on SSRs and hinder the further SSR expansion by introducing repeat interruptions to stabilize SSR loci. Furthermore, it was shown that some potential point mutations in the flanking regions are linked with new SSR repeat motif variation in almond and peach.

Alleles↗

PubMed2006

Haplotype diversity in "source-sink" dynamics of Escherichia coli urovirulence.

FimH, the mannose-specific, type 1 fimbrial adhesin of Escherichia coli, acquires amino acid replacements adaptive in extraintestinal niches (the genitourinary tract) but detrimental in the main habitat (the large intestine). This microevolutionary dynamics is reminiscent of an ecological "source-sink" model of continuous species spread from a stable primary habitat (source) into transient secondary niches (sink), with eventual extinction of the sink-evolved populations. Here, we have adapted two ecological analytical tools-diversity indexes DS and alpha--to compare size and frequency distributions of fimH haplotypes between evolutionarily conserved FimH variants ("source" haplotypes) and FimH variants with adaptive mutations (putative "sink" haplotypes). Both indexes show two- to threefold increased diversity of the sink fimH haplotypes relative to the source haplotypes, a pattern that ran opposite to those seen with nonstructural fimbrial genes (fimC and fimI) and housekeeping loci (adk and fumC) but similar to that seen with another fimbrial adhesin of E. coli, papG-II, also implicated in extraintestinal infections. The increased diversity of the sink pool of adhesin genes is due to the increased richness of the haplotypes (the number of unique haplotypes), rather than their evenness (the extent of similarity in relative abundances). Taken together, this pattern supports a continuous emergence and extinction of the gene alleles adaptive to virulence sink habitats of E. coli, rather than a one-time change in the habitat conditions. Thus, ecological methods of species diversity analysis can be successfully adapted to characterize the emergence of microbial virulence in bacterial pathogens subject to source-sink dynamics.

Adhesins, Escherichia coli↗

PubMed2005

Genetic diversity and genetic structure of an endangered species, Trillium tschonoskii.

The genetic diversity and genetic structure of Trillium tschonoskii (Maxim) were investigated using amplified fragment length polymorphism markers. Eight primer combinations were carried out on 105 different individuals sampled from seven populations. Of the 619 discernible DNA fragments generated, 169 (27.3%) were polymorphic. The percentage of polymorphic bands within populations ranged from 4.52 to 10.50. Genetic diversity (H(E)) within populations ranged from 0.0130 to 0.0379, averaging 0.0536 at the species level. Genetic differentiation among populations was detected based on Nei's genetic diversity analysis (53.03%) and analysis of molecular variance (AMOVA) (52.43%). AMOVA indicated significant genetic differentiation among populations (52.43% of the variance) and within populations (47.57% of the variance) (p < 0.0002). Gene flow was low (0.4429) among populations. Species breeding system and limited gene flow among populations are plausible reasons for the high genetic differentiation observed for this species. We propose an appropriate strategy for conserving the genetic resources of T. tschonoskii in China.

China↗

PubMed2006

Leadlikeness and structural diversity of synthetic screening libraries.

High program failure rates in the pharmaceutical industry have prompted the development of predictive software that can profile compound libraries as being 'druglike' (resembling existing drugs) and/or 'leadlike' (possessing the structural and physicochemical profile of a quality lead). In recent years, these two notions prompted pharmaceutical companies to clean up their corporate libraries of screening compounds. In order to maintain and expand the size and diversity of these corporate libraries, pharmaceutical companies still continue to add compounds to these, mainly by the acquisition of screening libraries. In this paper, we have analyzed 45 commercially available libraries, offered by suppliers of screening chemistry, for leadlikeness and diversity of the offered structures. To this end we have used a set of structural and physicochemical filters for leadlikeness that was developed in-house. These 45 supplier libraries contained a total of 5.3 million structures, of which 49% (2,592,778 structures) turned out to be unique, and only 12% (677,328 structures) were found to be both unique and leadlike. A diversity analysis revealed that big differences exist between the various offered libraries.

Chemistry, Pharmaceutical↗

PubMed2005

Patterns of genetic polymorphism at the 10 X-chromosome STR loci in Mongol population.

Genetic diversity at 10 X-chromosome STR loci has been approved and widely used for forensic science field. In this paper, we have studied this genetic diversity in various Mongol ethnic group with geographic backgrounds. Allele frequencies of 10 X-chromosome STR loci, including DXS7133, DXS6799, DXS8378, DXS7423, DXS6804, HPRTB, DXS7424, DXS7132, DXS6789 and DXS101, were obtained from healthy unrelated individuals (53 females and 47 males) of Mongol ethnic group lived in north China. Gene diversity analysis showed that the average heterozygosity was uniformly high (0.687) in the studied population. The coefficient of PIC was 0.99998.

China↗

PubMed2004

Conserved patterns in the evolution of Tribolium satellite DNAs.

Two satellite DNAs, TANAPH and TDEST, isolated from the beetle species Tribolium anaphe and Tribolium destructor, respectively, are characterized and compared with previously described Tribolium satellites, in order to deduce possible constraints on satellite sequence evolution between closely related species. Sequence diversity analysis of cloned monomers reveals the presence of variable and conserved segments in both satellites. In addition, non-random organization of As or Ts and their periodical distribution in the form of A or T >/=3 tracts, as well as CENP-B box-like motifs and dyad structures have been found in both satellites. Similar structural features are also present in satellites from other Tribolium species. We therefore propose that they, together with the observed non-constant rate of evolution along the satellite sequence, could be related to putative protein binding sites and suggest a possible selective pressure affecting these sequences. Tribolium satellites, including TANAPH and TDEST, are located in the pericentromeric heterochromatin of all chromosomes of the corresponding species. Since satellites from different species exhibit no significant sequence homology, we propose that they did not originate from a common ancestral sequence. More probably, they derive from simple sequence modules some of which could represent protein binding sites. Shuffling of simple sequence modules could generate different satellites, able to perform a similar role in different species.

Animals↗

PubMed2005

Sequence divergence and conservation in organizationally distinct subfamilies of Donax trunculus satellite DNA.

Characterization of a low-copy number DTF1 satellite DNA detected in the bivalve mollusk Donax trunculus revealed extensive grouping of monomer sequence variants into subfamilies identified by distinctive combinations of diagnostic nucleotides. It can be anticipated that a large number of subfamilies exists in the genome. In addition to the tandem organization of 169 bp long monomers, at least one subfamily was created through amplification of adjacent repeats in a higher order register. This complex satellite unit consists of two distinctive monomer variants that differ both in specific nucleotide changes and in a deleted segment partially substituted with a short unrelated sequence element. Most of the nucleotide substitutions differing between subfamilies are highly homogenized within a corresponding group of monomer variants, and intra-subfamily variability in general is low. Nucleotide diversity analysis of all sequenced variants of DTF1 satellite revealed the presence of two conserved segments, while the rest of the monomer sequence shows uniform and considerably higher level of variability. The persistence of conserved segments stands in contrast to the sequence and organizational divergence of monomer variant groups, and may indicate constraints in the evolution of DTF1 satellite repeats.

Amino Acid Sequence↗

PubMed2004

The distribution of serine proteinase inhibitors in seeds of the Asteridae.

The Asteridae is one of the most successful clades of flowering plants comprising some 80,000 species. Despite this diversity, analysis of seeds from 398 species (representing 8 orders, 32 families and 181 genera) showed just two major types of serine proteinase inhibitors (PI). PIs of the potato inhibitor I family were widely distributed. These had M(r) of 7000-7500 and were inhibitory to subtilisin and one or more other proteinases (but only rarely elastase). The second major group was TI related to the well-characterised Bowman-Birk inhibitors of legume seeds but these varied widely in their sequences and structure. In addition to these two groups of inhibitors, seeds of the Solanaceae also often contained PI of the potato inhibitor II family while some other asterids contained inhibitors whose relationships were not established.

Amino Acid Sequence↗

PubMed2006

A BAC-based contig map of the cynomolgus macaque (Macaca fascicularis) major histocompatibility complex genomic region.

The construction of a cynomolgus macaque (Macaca fascicularis, Mafa) BAC library for genomic comparison between rhesus and cynomolgus macaques is necessary to promote the cynomolgus macaque as one of the important experimental animals for future medical and biological research. In this paper, we constructed a cynomolgus macaque BAC library and a map of the MHC (Mafa) genomic region for comparison of the genomic organization and nucleotide similarities between the human, the chimpanzee, and the rhesus macaque. The BAC library consists of 221,184 clones with an average insert size of 83 kb, providing a sixfold coverage of the haploid genome. A total of 114 BAC clones and 54 PCR primer sets were used to construct a 4.3-Mb contig of the MHC region. Diversity analysis of genomic sequence from selected subregions of the MHC revealed that the cynomolgus sequence varied compared to rhesus macaque, human, and chimpanzee sequences by 0.48, 4.15, and 4.10%, respectively. From these findings, we conclude that the BAC library and Mafa genomic map are useful tools for genome analysis and will have important applications for comparative genomics and identifying regions of consequence in medical research.

Animals↗

PubMed2000

Chemoinformatics - similarity and diversity in chemical libraries.

Molecular similarity and molecular diversity techniques lie at the heart of attempts to design structurally diverse combinatorial libraries for the identification of novel bioactive compounds. Recent advances include the development of new types of selection algorithm, the validation of such algorithms, the use of filtering systems to screen out undesirable molecules prior to the design of a library, and the integration of similarity and diversity analysis with other methods for computer-aided molecular design.

Algorithms↗

PubMedDate not supplied

Visualizing substructural fingerprints.

Substructural fingerprints have proven very useful for chemical library and diversity analysis, but their high dimensionality makes them poorly suited to principal components analysis and to standard nonlinear mapping methods. By using a combination of optimizable K-dissimilarity selection (OptiSim) and a modified stress function that suppresses effects of distances that fall beyond a characteristic horizon, it is possible to relax principal components analysis coordinates into more consistently meaningful projections from fingerprint space into two dimensions. The nonlinear maps so obtained are useful for characterizing combinatorial libraries, for comparing sublibraries, and for exploring the distribution of biological properties across structural space.

Combinatorial Chemistry Techniques↗