Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Diversification”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,423 records · Page 79Linked to original sources

Parallel evolution in the V3 region of HIV type 1 after infection of hemophiliacs from a homogeneous source.

To determine the genetic diversification in the highly functional V3 loop, we followed up five hemophiliacs who were infected by a homogeneous HIV-1 population from a contaminated clotting factor lot. Initially, all patients displayed identical DNA sequences in this part of the proviral env gene. Therefore, this unique outbreak allows us to investigate the biological and genetic development of a common ancestor virus in different patients. A high degree of homology is maintained in the predominant sequences from 5 until 35 months after seroconversion. Only one patient showed a remarkable diversification 3 years postinfection. However, these genetic changes in the V3 region were not associated with disease progression. Discontinuous sequence changes were observed mainly in a region downstream of the V3 loop. Two positions in particular are involved in a sequence evolution within the V3 loop leading to the same amino acids in different patients. These directed changes occurred at sites that are reported to be critical for the specificity of antibodies (position 308) and viral cytopathicity (position 324). However, the parallel evolution was associated neither with differentiation of the viral phenotype nor with progression of the disease.

Amino Acid Sequence↗

Molecular characterization of Listeria monocytogenes of the serotype 4b complex (4b, 4d, 4e) from two turkey processing plants.

Most foodborne outbreaks of listeriosis have been found to involve a small number of closely related strains of Listeria monocytogenes serotype 4b. The ecology of these organisms and their reservoirs in nature or in the processing plant environment, however, remain poorly understood. Surveys of environmental samples from two turkey processing plants in the United States indicated presence of L. monocytogenes of the serotype 4b complex (serotype 4b and the closely related serotypes 4d and 4e). In addition, environmental and raw product samples from one plant repeatedly yielded isolates with genetic markers typical of two major serotype 4b epidemic clonal groups, ECI and ECII. The pulsed field gel electrophoresis (PFGE) profiles of these isolates, however, were clearly distinct from those of confirmed epidemic-associated strains. Furthermore, we observed minor but consistent differences in PFGE profiles of isolates that harbored ECI- or ECII-specific genetic markers, and that were obtained at different sampling times from the same plant. The findings suggest processing plant persistence (or repeated introductions) and genomic diversification of L. monocytogenes serotype 4b isolates that harbor ECI- or ECII-specific genetic markers. Such diversification would need to be taken into consideration in further efforts to elucidate the evolution and epidemiology of these organisms.

Animals↗

Involvement of closely related strains of a new clonal group of Listeria monocytogenes in the 1998-99 and 2002 multistate outbreaks of foodborne listeriosis in the United States.

In 1998-99, a multistate outbreak of listeriosis in the United States was associated with contaminated hot dogs and was caused by a strain of Listeria monocytogenes serotype 4b that had been only rarely encountered before in the national PulseNet database. Upon further characterization, the strains from this outbreak were designated as Epidemic Clone II (ECII). ECII isolates exhibited diversification in a genomic region ("region 18") that was otherwise conserved among L. monocytogenes of serotype 4b. Additional unique genetic markers were identified through genome sequencing of one of the isolates from the 1998-99 outbreak. In 2002, another multistate outbreak of listeriosis also involved bacteria of serotype 4b and was attributed to contaminated turkey deli meats. Molecular subtyping data revealed that the macrorestriction patterns of the isolates from the 1998-99 and 2002 outbreaks were closely related. In addition, the 2002 outbreak isolates harbored chromosomal genetic markers found to be unique to, and typical of, the 1998-99 outbreak isolates, including diversification in genomic region 18. Macroarray- based subtyping using chromosomal sequences confirmed the close genetic relatedness between the isolates from the two outbreaks. Genomic content was highly conserved among isolates from each outbreak, with differences detected only in prophage and internalin-like gene sequences. However, since these differences were observed among isolates from each of the outbreaks, they did not differentiate the 1998-99 isolates as a group from those of the 2002 outbreak. Two of 15 randomly chosen serotype 4b clinical isolates from a non-outbreak period (calendar year 2003) appeared to be closely related to the 1998-99 and 2002 outbreak isolates. These findings suggest that both multistate outbreaks of listeriosis in the United States involved closely related members of a single clonal group (ECII) that had not been identified in outbreaks prior to 1998. Since the outbreaks involved different food vehicles and processing plants, the findings suggest establishment of ECII in a still unidentified reservoir in the United States, from which the organisms were introduced to different processing plants.

Animals↗

SoDA: implementation of a 3D alignment algorithm for inference of antigen receptor recombinations.

MOTIVATION: The antigen receptors of adaptive immunity-T-cell receptors and immunoglobulins-are encoded by genes assembled stochastically from combinatorial libraries of gene segments. Immunoglobulin genes then experience further diversification through hypermutation. Analysis of the somatic genetics of the immune response depends explicitly on inference of the details of the recombinatorial process giving rise to each of the participating antigen receptor genes. We have developed a dynamic programming algorithm to perform this reconstruction and have implemented it as web-accessible software called SoDA (Somatic Diversification Analysis). RESULTS: We tested SoDA against a set of 120 artificial immunoglobulin sequences generated by simulation of recombination and compared the results with two other widely used programs. SoDA inferred the correct gene segments more frequently than the other two programs. We further tested these programs using 30 human immunoglobulin genes from Genbank and here highlight instances where the recombinations inferred by the three programs differ. SoDA appears generally to find more likely recombinations.

Algorithms↗

Population structure in Daphnia obtusa: quantitative genetic and allozymic variation.

Quantitative genetic analyses for body size and for life history characters within and among populations of Daphnia obtusa reveal substantial genetic variance at both hierarchical levels for all traits measured. Simultaneous allozymic analysis on the same population samples indicate a moderate degree of differentiation: GST = 0.28. No associations between electrophoretic genotype and phenotypic characters were found, providing support for the null hypothesis that the allozymic variants are effectively neutral. Therefore, GST can be used as the null hypothesis that neutral phenotypic evolution within populations led to the observed differentiation for the quantitative traits, which I call QST. The results of this study provide evidence that natural selection has promoted diversification for body size among populations, and has impeded diversification for relative fitness. Analyses of population differentiation for clutch size, age at reproduction, and growth rate indicate that neutral phenotypic evolution cannot be excluded as the cause.

Analysis of Variance↗

Heterochromatic Stellate gene cluster in Drosophila melanogaster: structure and molecular evolution.

The 30-kb cluster comprising close to 20 copies of tandemly repeated Stellate genes was localized in the distal heterochromatin of the X chromosome. Of 10 sequenced genes, nine contain undamaged open reading frames with extensive similarity to protein kinase CK2 beta-subunit; one gene is interrupted by an insertion. The heterochromatic array of Stellate repeats is divided into three regions by a 4.5-kb DNA segment of unknown origin and a retrotransposon insertion: the A region (approximately 14 Stellate genes), the adjacent B region (approximately three Stellate genes), and the C region (about four Stellate genes). The sequencing of Stellate copies located along the discontinuous cluster revealed a complex pattern of diversification. The lowest level of divergence was detected in nearby Stellate repeats. The marginal copies of the A region, truncated or interrupted by an insertion, escaped homogenization and demonstrated high levels of divergence. Comparison of copies in the B and C regions, which are separated by a retrotransposon insertion, revealed a high level of diversification. These observations suggest that homogenization takes place in the Stellate cluster, but that inserted sequences may impede this process.

Amino Acid Sequence↗

Genotypic stability, segregation and selection in heteroplasmic human cell lines containing np 3243 mutant mtDNA.

The mitochondrial genotype of heteroplasmic human cell lines containing the pathological np 3243 mtDNA mutation, plus or minus its suppressor at np 12300, has been followed over long periods in culture. Cell lines containing various different proportions of mutant mtDNA remained generally at a consistent, average heteroplasmy value over at least 30 wk of culture in nonselective media and exhibited minimal mitotic segregation, with a segregation number comparable with mtDNA copy number (>/=1000). Growth in selective medium of cells at 99% np 3243 mutant mtDNA did, however, allow the isolation of clones with lower levels of the mutation, against a background of massive cell death. As a rare event, cell lines exhibited a sudden and dramatic diversification of heteroplasmy levels, accompanied by a shift in the average heteroplasmy level over a short period (<8 wk), indicating selection. One such episode was associated with a gain of chromosome 9. Analysis of respiratory phenotype and mitochondrial genotype of cell clones from such cultures revealed that stable heteroplasmy values were generally reestablished within a few weeks, in a reproducible but clone-specific fashion. This occurred independently of any straightforward phenotypic selection at the individual cell-clone level. Our findings are consistent with several alternate views of mtDNA organization in mammalian cells. One model that is supported by our data is that mtDNA is found in nucleoids containing many copies of the genome, which can themselves be heteroplasmic, and which are faithfully replicated. We interpret diversification and shifts of heteroplasmy level as resulting from a reorganization of such nucleoids, under nuclear genetic control. Abrupt remodeling of nucleoids in vivo would have major implications for understanding the developmental consequences of heteroplasmy, including mitochondrial disease phenotype and progression.

Base Sequence↗

Sequence variation at two eosinophil-associated ribonuclease loci in humans.

Host defense against invading pathogens is of great importance to the survival of higher organisms. We have been studying the evolution of mammalian eosinophil-associated ribonucleases (EARs), which are members of the ribonuclease A superfamily with known antipathogen activities. Earlier studies showed that positive selection promoted rapid diversification of paralogous EAR genes in both primates and rodents. Intraspecifically, however, it is unknown whether these genes also have divergent alleles. The recent discovery that the gene repertoire of the EAR family is much larger in rodents than in primates has led us to consider the possibility that primates maintain a large number of polymorphic alleles to compensate for a smaller gene repertoire. Here we present sequences of 2417 nucleotides at the two EAR loci, the eosinophil-derived neurotoxin (EDN, RNase 2) and eosinophil cationic protein (ECP, RNase 3), from >50 human individuals. Our data demonstrate that the nucleotide diversities (0.06-0.11%) at these loci are typical for human nuclear genes, thus permitting us to reject this polymorphism hypothesis. No significant departure from neutrality is noted and no signs of overdominant selection are observed. Similar patterns were observed in a preliminary study of chimpanzees. In summary, our results suggest that the antipathogen functions of the primate EARs are conserved after they are established and that these proteins are not currently undergoing rapid diversification in response to challenge from invading microorganisms.

Alleles↗

The CDY-related gene family: coordinated evolution in copy number, expression profile and protein sequence.

Theories predict that the long-term survival of duplicated genes requires their functional diversification, which can be accomplished by either subfunctionalization (the partitioning of ancestral functions among duplicates) or neofunctionalization (the acquisition of novel function). Here, we characterize the CDY-related mammalian gene family, focusing on three aspects of its evolution: gene copy number, tissue expression profile and amino acid sequence. We show that the progenitor of this gene family arose de novo in the mammalian ancestor via domain accretion. This progenitor later duplicated to generate CDYL and CDYL2, two autosomal genes found in all extant mammals. Prior to human-mouse divergence (and perhaps preceding the eutherian radiation), a processed CDYL transcript retroposed onto the Y chromosome to create CDY, the Y-linked member of the family. In the simian lineage, CDY was retained and subsequently amplified on the Y. In non-simian mammals, however, CDY appears to have been lost. The retention of the Y-linked CDY genes in simians spurred the process of subfunctionalization and possibly neofunctionalization. Subfunctionalization is evidenced by the observation that simian CDYL and CDYL2 retained their somatic housekeeping transcripts but lost the spermatogenic transcripts to the newly arisen CDY. Neo-functionalization is suggested by the rapid evolution of the CDY protein sequence. Thus, the CDY-related family offers an instructive example of how duplicated genes undergo functional diversification in both expression profile and protein sequence. It also supports the previously postulated notion that there is a tendency for spermatogenic functions to transfer from autosomes to the Y chromosome.

Amino Acid Sequence↗

Evolutionary comparison of the avian IgL locus: combinatorial diversity plays a role in the generation of the antibody repertoire in some avian species.

Immunoglobulin light chain (IgL) diversity is generated in the chicken by recombination between the single functional variable (VL) and joining (JL) gene segments and subsequent somatic diversification of the rearranged VL region. In order to determine whether these events are a general feature of avian IgL genes, we analyzed the organization and recombinatorial characteristics of the IgL loci of several other avian species. Southern blot analysis of bursal and germline DNA using chicken VL and constant (CL) probes revealed that the IgL loci of quail, mallard duck, pigeon, turkey, cormorant, and hawk consist of a family of VL elements, but undergo a single major rearrangement event similar to that observed in chickens. In contrast, several rearrangements were observed in the Muscovy duck locus. A phage clone containing a 26 kb insert that hybridized to VL and CL probes was isolated from a Muscovy duck erythrocyte DNA genomic library. Nucleotide sequencing revealed that the clone contained a single JL-CL region flanked on the 5' side by five VL segments. Unlike the chicken, two of the VL segments (VL1, VL5) appear to be functional. The remaining three VL segments are pseudogenes that lack promoter and leader sequences, but one of these (psi VL3) has recombination signal sequences. Overall, these data indicate that rearrangement of one VL gene segment is a general feature of the IgL locus in many avian species. In these species, the presence of a family of VL elements that do not rearrange suggests that a pseudogene pool may be available for somatic diversification by gene conversion. The organization of the Muscovy duck IgL locus suggests that additional combinatiorial diversity has evolved independently in some avian species.

Amino Acid Sequence↗

Gene conversion-like sequence transfers in a mouse antibody transgene: antigen selection allows sensitive detection of V region interactions based on homology.

Gene conversion is important for antibody diversification in chickens, rabbits and cows. In mice, however, conversion events appear to be infrequent among endogenous antibody genes. DNA sequence transfer events that resemble gene conversions have been reported for a mouse H chain transgene (VVC(mu)) that contains two closely spaced homologous VDJ segments. Surprisingly, these reported VVC(mu) sequence transfers were found frequently among mouse B cells responding to immunization. Transgene sequence transfers could be occurring at high frequency in responding VVC(mu) B cells or could be occurring at lower frequency with subsequent amplification by preferential antigen selection. To distinguish these possibilities, we have analyzed a second transgene (InVVC(mu)) that is identical to VVC(mu) except that the two VDJ regions have been exchanged in position. We find that transgene sequence transfers are much less frequent among responding B cells in InVVC(mu) mice, demonstrating the importance of selection in the frequent transgene conversions observed in VVC(mu) mice. These results suggest that mice, like other species, can use gene conversion to diversify antibodies. Such diversification events are apparently infrequent, however, and might only be detected among endogenous Ig genes with a favorable arrangement of V genes and an antigenic stimulation that selects cells with conversions. For both VVC(mu) and InVVC(mu) mice, conversion-like sequence transfers are strongly correlated with somatic hypermutation. Based on these results, we hypothesize that, in mice, gene conversions represent infrequent alternative reactions of a homology-based DNA repair process that is central in the somatic hypermutational mechanism.

Animals↗

Somatic hypermutation of VHS107 genes is not associated with gene conversion among family members.

Murine B cells proliferating in the germinal centers of peripheral lymphoid tissue accumulate mutations in their rearranged variable regions, a diversification process which contributes to affinity maturation of the antibody response. The highly targeted nature of the hypermutation process could be explained by a somatic gene conversion mechanism. Well characterized examples of such an activity in B cells are seen during diversification of the chicken and rabbit Ig repertoires. The genomic organization, low complexity and high degree of homology exhibited by the four members of the murine VHS107 gene family suggested that these gene segments may be suitable candidates for the search of gene conversion events derived from upstream VHS107 counterparts. After an immune response to a complex T cell-dependent antigen (sheep red blood cells), rearranged V13, V11 and V1 genes were isolated from splenic extrafollicular and germinal center B cells. Extensive somatic mutation was evident in V11 and V1 sequences. When these sequences were examined, as well as V1 sequences isolated from phosphorylcholine-specific hybridomas, the observed nucleotide changes were not associated with any gene conversion between family members, suggesting instead that they arose by a mechanism which introduces point mutations.

Animals↗

Calibration and error in placental molecular clocks: a conservative approach using the cetartiodactyl fossil record.

The nature of the molecular and fossil record and their limitations must be ascertained in order to gain the most precise and accurate evolutionary timescale using genetic information. Yet the majority of such timescales are based on point estimates using fossils or the molecular clock. Here we document from the primary literature minimum and maximum fossil age estimates of the divergence of whales from artiodactyls, a commonly used anchor point for calibrating both mitogenomic and nucleogenomic placental timescales. We applied these reestimates to the most recently established placental timescale based on mitochondrial rRNA and several nuclear loci, and present an attempt to account for both genetic and fossil uncertainty. Our results indicate that disregard for fossil calibration error may inflate the power of the molecular clock when testing the time of ordinal diversification in context with the K-T boundary. However, the early history of placentals, including their superordinal diversification, remained in the Cretaceous despite a conservative approach. Our conclusions need corroboration across other frequently used fossil anchor points, but also with more genetic partitions on the linear relationship between molecular substitutions and geologic time.

Animals↗

Paleobiogeography of two Iberian endemic cyprinid fishes (Chondrostoma arcasii-Chondrostoma macrolepidotus) inferred from mitochondrial DNA sequence data.

We tested different hypotheses related to the origin and evolution of the endemic Iberian fishes Chondrostoma arcasii and Chondrostoma macrolepidotus from northern and central regions of the Iberian Peninsula. We evaluated the monophyly of the populations within each species and sought to determine if diversification of the populations coincided in time with the formation of the Iberian drainages dating back to the upper Pliocene (2.5-1.8 million years ago). A molecular phylogenetic analysis of the mitochondrial cytochrome b gene showed that the different populations of the northern Iberian Peninsula are clustered into five phylogroups and do not fit into the dichotomy C. arcasii-C. macrolepidotus. We propose that species differentiation occurred prior to the upper Pliocene formation of the present hydrographic basins and that endorheic basins, a system of inland lakes found in Spain during the Mio-Pliocene, played an important role in this diversification and differentiation process.

Animals↗

Beyond the CO-FT regulatory module: E1 and PHYA emerge as players in photoperiodic regulation of flowering in legumes.

The legume family (Fabaceae) is the third largest in plants and includes several crop species that are able to fix nitrogen, promote soil health, and contribute to food security worldwide. Recent progress in legume genetics and genomics allowed the identification of photoperiod-dependent flowering loci, which were incorporated into specific signalling networks. Functional characterization of these regulators revealed new roles for known photoreceptors such as phytochrome A, and it also identified legume-specific B3 domain transcriptional factors (E1 and E1-like proteins). This suggests some diversification from the traditional CONSTANS-FLOWERING LOCUS T module present in other angiosperms. Although most of the findings discussed herein pertain to species from the two main legume clades, the Galegoids (e.g. alfalfa, clover, and pea) and the Phaseoloids (e.g. common bean, soybean, cowpea, and pigeon pea), research on flowering regulation in the basal Genistoid clade (e.g. lupins) will also be addressed. We propose that functional diversification of photoperiod-dependent flowering strategies in the different legume species could have contributed to their environmental adaptation and allowed their geographical expansion and success worldwide.

Photoperiod↗

Birth-and-death evolution with strong purifying selection in the histone H1 multigene family and the origin of orphon H1 genes.

Histones are small basic nuclear proteins with critical structural and functional roles in eukaryotic genomes. The H1 multigene family constitutes a very interesting histone class gathering the greatest number of isoforms, with many different arrangements in the genome, including clustered and solitary genes, and showing replication-dependent (RD) or replication-independent (RI) expression patterns. The evolution of H1 histones has been classically explained by concerted evolution through a rapid process of interlocus recombination or gene conversion. Given such intriguing features, we have analyzed the long-term evolutionary pattern of the H1 multigene family through the evaluation of the relative importance of gene conversion, point mutation, and selection in generating and maintaining the different H1 subtypes. We have found the presence of an extensive silent nucleotide divergence, both within and between species, which is always significantly greater than the nonsilent variation, indicating that purifying selection is the major factor maintaining H1 protein homogeneity. The results obtained from phylogenetic analysis reveal that different H1 subtypes are no more closely related within than between species, as they cluster by type in the topologies, and that both RD and RI H1 variants follow the same evolutionary pattern. These findings suggest that H1 histones have not been subject to any significant effect of interlocus recombination or concerted evolution. However, the diversification of the H1 isoforms seems to be enhanced primarily by mutation and selection, where genes are subject to birth-and-death evolution with strong purifying selection at the protein level. This model is able to explain not only the generation and diversification of RD H1 isoforms but also the origin and long-term persistence of orphon RI H1 subtypes in the genome, something that is still unclear, assuming concerted evolution.

Amino Acid Sequence↗

"Species" radiations of symbiotic dinoflagellates in the Atlantic and Indo-Pacific since the Miocene-Pliocene transition.

Endosymbiotic dinoflagellates, or "zooxanthellae," are required for the survival of a diverse community of invertebrates that construct and dominate shallow, tropical coral reef ecosystems. Molecular systematics applied to this once understudied symbiont partner, Symbiodinium spp., divide the group into divergent lineages or subgeneric "clades." Within each clade, numerous closely related "types," or species, exhibit distinctive host taxon, geographic, and/or environmental distributions. This diversity is greatest in clade C, which dominates the Indo-Pacific host fauna and shares dominance in the Atlantic-Caribbean with clade B. Two "living" ancestors in this group, C1 and C3, are common to both the Indo-Pacific and Atlantic-Caribbean. With these exceptions, each ocean possesses a diverse clade C assemblage that appears to have independently evolved (adaptively radiated) through host specialization and allopatric differentiation. This phylogeographic evidence suggests that a worldwide selective sweep of C1/C3, or their progenitor, must have occurred before both oceans separated. The probable timing of this event corresponds with the major climactic changes and low CO(2) levels of the late Miocene and/or early Pliocene. Subsequent bursts of diversification have proceeded in each ocean since this transition. An ecoevolutionary expansion to numerous and taxonomically diverse hosts by a select host-generalist symbiont followed by the onset of rapid diversification suggests a radical process through which coral-algal symbioses respond and persist through the vicissitudes of planetary climate change.

Adaptation, Biological↗

Origin and molecular evolution of receptor tyrosine kinases with immunoglobulin-like domains.

Receptor tyrosine kinases (RTKs) are involved in the control of fundamental cellular processes in metazoans. In vertebrates, RTK could be grouped in distinct classes based on the nature of their cognate ligand and modular composition of their extracellular domain. RTK with immunoglobulin-like domains (IG-like RTK) encompass several RTK classes and have been found in early metazoans, including sponges. Evolution of IG-like RTK is characterized by extended molecular and functional diversification, which prompted us to study their evolutionary history. For that purpose, a nonredundant data set including annotated protein sequences of IG-like RTK (n = 85) was built, representing 19 species ranging from sponges to humans. Phylogenetic trees were generated from alignment of conserved regions using maximum likelihood approach. Molecular phylogeny strongly suggests that IG-like RTK diversification occurred according to a complex scenario. In particular, we propose that specific cis duplications of a common ancestor to both platelet-derived growth factor receptor (class III) and vascular endothelial growth factor receptor (class V) families preceded two trans duplications. In contrast, other IG-like RTK genes, like Musk and PTK7, apparently did not evolve by duplications, whereas fibroblast growth factor receptors (class IV) evolved through two rounds of trans duplications. The proposed model of IG-like RTK evolution is supported by high bootstrap values and by the clustering of genes encoding class III and class V RTKs at specific chromosomal locations in mouse and human genomes.

Animals↗