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At least 19 recordsLinked to original sources
PubMed2026

The Evolutionary Significance of Leaf Nodulation: Evidence from Ardisia and Its Relatives (Primulaceae: Myrsinoideae).

Interactions between plants and microorganisms have long been a central topic in biological research. Bacterial symbiosis on leaf surfaces represents a distinctive and mutually beneficial system within the phyllosphere microbiome. Leaf nodules are the visible manifestation of the symbiosis and confer ecological advantages to host plants by enhancing host resistance against pathogens and herbivores. It has been hypothesized that these advantages promote higher diversification rates in host lineages, but this remains uncertain. Ardisia subg. Crispardisia and its close relatives (Amblyanthopsis and Amblyanthus) within Primulaceae are typical plant groups with leaf nodule symbiosis, making them an ideal system for testing this hypothesis. In this study, we conducted extensive sampling of "Ardisioids" (Ardisia and its allies) and reconstructed their phylogenetic relationships and evolutionary history using plastid genomes and nuclear datasets (i.e., nuclear ribosomal DNA (nrDNA) and genome-wide single nucleotide polymorphisms (SNPs)). We clarified the phylogenetic positions of several "Ardisioids" genera (e.g., Sadiria, Tapeinosperma, Amblyanthus, and Amblyanthopsis) and multiple subgenera within Ardisia. We further detected a rapid radiation during the middle Miocene in Ardisia and its allies. Notably, we found that the leaf-nodulated clade appears to have originated during this period, approximately 11-8 Ma. BAMM (Bayesian Analysis of Macroevolutionary Mixtures) analyses revealed elevated diversification rates in leaf-nodulated lineages, while HiSSE (Hidden State Speciation and Extinction) analyses indicated that leaf nodule symbiosis might have increased speciation rates without significantly affecting extinction rates. These results provide strong evidence that leaf nodule symbiosis, together with other abiotic and biotic factors, represents a key evolutionary innovation that has promoted diversification in Ardisia and its close relatives.

diversification rate↗
PubMed1992

High rate of diversification and reversal among subclones of neoplastically transformed NIH 3T3 clones.

NIH 3T3 cells undergo neoplastic transformation when exposed to conditions of moderate physiological growth constraint. One of several characteristics of this transformation that indicates its adaptational nature is its gradual reversibility under conditions of unconstrained growth. We explored the origins of reversibility by isolating cells from each of three highly transformed foci and comparing their focus-forming capacity with that of derivative clones and subclones. A high proportion of the parental cells made dense foci. Six of the nine clones obtained from the three foci produced foci, though the percentage varied widely. The other three clones produced no foci at all. The transformed clones were subcloned and analyzed to evaluate the possibility that the negative clones were genuine revertants, rather than being derived from a small minority of nontransformed cells surrounding or underlying the original foci. In each case the subclones varied widely in the percentage of focus-forming cells and the average was much lower than the parental clone from which they were derived. Indeed, 15 of the 53 subclonal populations produced no foci. The high degree of heterogeneity, including complete reversal of focus-forming capacity, provides additional support for the hypothesis that "spontaneous" transformation is driven by an adaptive response to moderate growth constraint rather than by one or more effectively irreversible mutations.

3T3 Cells↗
PubMed1985

Comparative analysis of repeated sequences in rat apolipoproteins A-I, A-IV, and E.

To understand the structural, functional, and evolutionary relationships among the principal protein components of rat high density lipoprotein particles, we undertook a systematic comparative analysis of the primary structures of apolipoproteins (apo)-A-I, -A-IV, and -E. Human apo-A-I and rat apo-A-IV have been shown previously to contain repeated sequences that presumably arose by intragenic duplication of 11- or 22-amino acid amphipathic segments. For apo-A-I, these segments are thought to be the structures responsible for lipid binding and activation of lecithin:cholesterol acyltransferase. From an analysis of the sequence of a full-length cDNA clone, rat apo-A-I is shown to contain eight tandem repetitions of a 22-amino acid segment. However, compared with human apo-A-I, the rat protein has undergone three deletions, two of which involve multiple amino acids in the repeated sequence domain. This disruption of the periodic structure of the protein raises the possibility of species-specific variation in the ability of rat apo-A-I to interact with high density lipoproteins and activate lecithin:cholesterol acyltransferase. Statistical analysis of the structure and organization of repeated sequences in apo-A-I, -A-IV, and -E demonstrates that all three proteins are paralogous members of a dispersed gene family. Despite overall similarity in sequence organization, different portions of these sequences have evolved at different rates. Diversification of a duplicated ancestral sequence has resulted in three lipid-binding proteins with distinct and shared functions.

Amino Acid Sequence↗
PubMed1991

A mathematical model of vaccination against HIV to prevent the development of AIDS.

Vaccination and post-exposure immunization against the human immunodeficiency viruses (HIV-1 and HIV-2) faces the problem of the extensive genetic and antigenic variability of these viruses. This raises the question of what fraction of all possible antigen strains of the virus must be recognized by the immune response to a vaccine to prevent development of acquired immunodeficiency disease (AIDS). The success of a vaccine can depend on the variability of the target epitopes. The different HIV variants must be suppressed faster than new escape mutants can be produced. In this paper the antigenic variation of HIV during an individual infection is described by a stochastic process. The central assumption is that antigenic drift is important for the virus to survive immunological attack and to establish a persistent infection that leads to the development of AIDS after a long incubation period. The mathematical analysis reveals that the fraction of antigenic variants recognized by the immune response, that is induced by a successful immunogen, must exceed 1-1/R, where R is the diversification rate of the virus population. This means that if each HIV strain can produce, on average, five new escape mutants, then more than 80% of the possible variants must be covered by the immunogen. A generic result of the model is that, no matter how immunogenic a vaccine is, it will fail if it does not enhance immune attack against a sufficiently large fraction of strains. Furthermore, it is shown that the timing of the application of post-exposure immunization is important.

AIDS Vaccines↗
PubMed2025

The effects of cryptic diversity on diversification dynamics analyses in Crocodylia.

Incomplete taxon sampling due to underestimation of present-day biodiversity biases diversification analysis by favouring slowdowns in speciation rates towards the recent time. For instance, in diversification dynamics studies in Crocodylia, long-term low net-diversification rates and slowdowns in speciation rates have been suggested to characterize crocodylian evolution. However, crocodylian cryptic diversity has never been considered. Here, we explore the effects of incorporating cryptic diversity into a diversification dynamics analysis of extant crocodylians. We inferred a time-calibrated cryptic-species-level phylogeny using cytochrome b sequences of 45 lineages compared with the formally recognized 26 crocodylian species. Diversification rate estimates using the cryptic-species-level phylogeny show increasing speciation and net-diversification rates towards the present time, which contrasts with previous findings. Cryptic diversity should be considered in future macroevolutionary analyses; however, the representation of cryptic extinct taxa represents a major challenge. Additionally, further investigation of crocodylian diversification dynamics under different underlying genomic data is encouraged upon advances in population genetics. Our case study adds to the diversification dynamics knowledge of extant taxa and demonstrates that cryptic species and robust taxonomic assessment are essential to study recent biodiversity dynamics with broad implications for evolutionary biology and ecology.

Animals↗
PubMed1988

Maintenance of multiplication rate stability by cell populations in the face of heterogeneity among individual cells.

We addressed the question of how a population of cells can maintain a constant multiplication rate given the heterogeneity of its individual members. Using the NIH 3T3 line of mouse embryo cells, comparisons were made of multiplication rates between offspring subclones and the parental clones from which the subclones were derived. Parents at all levels of multiplication rate produced offspring with a wide range of multiplication rates. Offspring from parent cells with the highest growth rates rarely exceeded their parents in rate of multiplication. Offspring from slow-growing parents, however, often exceeded the parents. It is concluded that the multiplication of NIH 3T3 populations represents constant diversification in multiplication rate: heterogeneous parents producing heterogeneous offspring. Population growth rates can remain stable because the fastest-growing parents generally produce offspring that multiply slower than the parents while the slowest parents often produce offspring that multiply faster than the parents.

Animals↗
PubMed1992

Genetic variation and quasi-species.

During the past year the relative fitness, that is, overall replication ability, and the fitness gain of animal virus variants have been quantified, providing new insight into the dynamics for the generation of RNA virus quasi-species. Measurements of mutant frequencies and rates of genetic diversification have confirmed the extreme complexity of RNA virus and retrovirus populations.

Genetic Variation↗
PubMed1986

Temporal scaling of molecular evolution in primates and other mammals.

Molecular clocks are routinely tested for linearity using a relative rate test and routinely calibrated against the geological time scale using a single or average paleontologically determined time of divergence between living taxa. The relative rate test is a test of parallel rate equality, not a test of rate constancy. Temporal scaling provides a test of rates, where scaling coefficients of 1.0 (isochrony) represent stochastic rate constancy. The fossil record of primates and other mammals is now known in sufficient detail to provide several independent divergence times for major taxonomic groups. Molecular difference should scale negatively or isochronically (scaling coefficients less than 1.0) with divergence time: where two or more divergence times are available, molecular difference appears to scale positively (scaling coefficient greater than 1.0). A minimum of four divergence times are required for adequate statistical power in testing the linear model: scaling is significantly nonlinear and positive in six of 11 published investigations meeting this criterion. All groups studied show some slowdown in rates of molecular change over Cenozoic time. The break from constant or increasing rates during the Mesozoic to decreasing rates during the Cenozoic appears to coincide with extraordinary diversification of placental mammals at the beginning of this era. High rates of selectively neutral molecular change may be concentrated in such discrete events of evolutionary diversification.

Amino Acid Sequence↗
PubMed1987

Tumor cell instability, diversification, and progression to the metastatic phenotype: from oncogene to oncofetal expression.

It is proposed that tumor cell instability and the expression of cellular diversification mechanisms ensure that malignant neoplasms contain heterogeneous, phenotypically diverse tumor cell subpopulations. In such potentially unstable cellular mixtures of tumor cell phenotypes, some malignant cells may ultimately evolve with the most favorable properties for their progression to metastatic cells. Rates of cellular phenotypic instability and phenotypic diversification as well as their underlying causes appear to vary greatly among different tumor cells, and they are probably modulated by further genetic and chromosome changes and more frequently by intra- and extracellular epigenetic events that also differ, depending on the nature of the tumor cells and their cellular and microenvironmental interactions. Diversified malignant cells are characterized by quantitative and perhaps a few qualitative differences in gene expression, which may explain their abilities to undergo rapid changes in phenotypic properties. As tumor diversification and selection proceed uniquely in vivo, highly malignant cell subpopulations may eventually become dominant and gradually and independently lose their cellular and microenvironmental responsiveness. Tumor cell diversification mechanisms may be similar or identical to normal developmentally regulated diversification mechanisms that are used during embryonic and postembryonic cell diversification and development.

Animals↗
PubMed2026

The convergent evolution of the pelvic suction cup: A unique key innovation in spiny-finned fishes.

Key innovations open ecological opportunities and can redirect evolutionary trajectories. In spiny-finned fishes, the pelvic suction cup-a fused adhesive structure formed from the pelvic fins and supported by a modified girdle-appears to be one such trait. Using a novel 960-species phylogeny spanning 940 exons and 67 newly sequenced snailfish genomes, we show that the suction cup evolved independently three times across lineages separated by over 100 million years. By enabling adhesion in high-energy habitats such as tide pools and waterfalls, the suction cup set the stage for body depression and accompanying shifts in scales, teeth, and clade-specific ecofunctional profiles. Comparative analyses reveal convergence in a distinctive region of morphospace and body-shape evolution accelerated two- to fivefold. Diversification analyses uncover heterogeneous but elevated rates, with a clear burst in rock-climbing gobies associated with suction cup evolution. By opening novel habitats and fostering phenotypic novelty, the suction cup emerges as a key innovation that reshaped spiny-finned fish evolution.

Animals↗
PubMed1975

Stage-specific switches in histone synthesis during embryogenesis of the sea urchin.

Histones H2A and H2B of the sea urchin embryo have been resolved by new methods into components that are synthesized at different stages of development. One form of H2A and one form of H2B are synthesized only during the period from fertilization to the blastula stage. Subsequently, two other types of H2A and H2B molecules are synthesized. In addition, a histonelike protein was detected which is synthesized only from fertilization until the 16-cell stage when the synthesis of still another H2A-like protein begins. None of the late-appearing forms are derived from histone polypeptide chains synthesized earlier in development. Since the early components do not disappear after their synthesis stops, these modulations of histone synthesis lead to an increase in histone multiplicity, concomitant with the beginning of cell diversification and a decrease in cell division rate.

Age Factors↗
PubMed1992

Transfection of activated c-H-rasEJ/pSV2neo or pSV2neo genes into rat mammary cells: rapid stimulation of clonal diversification of spontaneous metastatic and cell-surface properties.

We examined whether the conversion of benign rat mammary cells to metastatic cells by transfection of c-H-rasEJ/pSV2neo or control pSV2neo genes results in rapid stimulation of diversification of cellular phenotypes. Transfection of c-H-rasEJ into twice-cloned, stable (greater than 1 year) rat mammary MTC.4 cells, followed quickly by cell cloning, revealed differences in transfected oncogene copy numbers and expression of p21rasEJ. No correlation between c-H-rasEJ copy numbers or the cellular amounts of p21rasEJ or total p21ras and spontaneous metastatic potentials was found. By subcloning transfected cells as soon as possible after gene transfer, we found some rearrangements and amplifications of c-H-rasEJ and heterogeneous spontaneous metastatic potentials. In addition, the expression of the mammary tumor metastasis-associated cell-surface glycoprotein gp580 on untransfected and transfected MTC.4 cells indicated that the cell populations of higher metastatic potential were also more diverse in their cell-to-cell antigen expression than untransfected or non-metastatic, transfected MTC.4 cells. In contrast, the expression of a putative metastasis-suppressor gene, nm23, was unchanged after transfection and subcloning. Control pSV2neo transfections or calcium phosphate treatment alone also resulted in the generation of cellular heterogeneity, although at an apparently lower frequency than c-H-rasEJ transfections, suggesting that transfection of activated, dominantly acting oncogenes, or in some cases control genes, can result in destabilization of transfected cells, rapid diversification and generation of heterogeneity in growth rate, spontaneous metastatic potential and antigen expression.

Animals↗
PubMed1988

Corporate diversification: expectations and outcomes.

A review of the research concerning the diversification experience of firms in other industries shows that expectations of higher profit rates and lower risk are not entirely realistic. However, there are many ways in which the probability of financially successful diversification may be increased.

Evaluation Studies as Topic↗
PubMed1992

Origin of the Romany gypsies--genetic evidence.

Genetic heterogeneity and affinity was examined between nine Romany speaking gypsy populations and two of their possible ancestral populations from India. For AB0, Rhesus (D), MN and HP systems there exists a conclusive heterogeneity among these populations. Three gypsy populations from Western Europe (English, Welsh and Swedish) are genetically distinct from the rest of the East European gypsies and the populations of India analysed in this investigation. Overall the genetic differentiation among these populations is moderately high (RST = 0.029). The results also indicate the relative close relationship among the East gypsies and the two selected nomadic populations of India. The factors responsible for the moderate diversification of the East European gypsies may be high rate of migration, isolation and random drift, while among the Western gypsy populations admixture seems to be an important differentiation factor.

Adult↗
PubMed2026

Deconvolution of evolutionary architecture unmasks a high-risk, subclonal-rich subtype in treatment-naive small cell lung cancer.

BACKGROUND: Intratumoral heterogeneity (ITH) drives therapeutic resistance in small cell lung cancer (SCLC). However, conventional single-sample analysis has limited horizontal, cross-patient comparisons, leaving the overarching evolutionary architecture in treatment-naive tumors poorly understood. This study aims to deconvolve these architectures to identify clinically relevant evolutionary subtypes. METHODS: We analyzed whole-exome sequencing data from 41 treatment-naive SCLC patients. To overcome the cross-patient comparability bottleneck, we developed a novel probabilistic framework using a refined Gaussian Mixture Model (GMM). This standardized subclonal structures into four hierarchical strata, enabling the identification of evolutionary subtypes via unsupervised clustering. To address the scarcity of SCLC public data, prognostic concordance was robustly explored in The Cancer Genome Atlas (TCGA) lung squamous cell carcinoma (LUSC) based on shared smoking etiology, with lung adenocarcinoma (LUAD) serving as a negative control. RESULTS: The cohort robustly segregated into "Clonal-dominant" (Group 1, n=28) and "Subclonal-rich" (Group 2, n=13) subtypes. Group 1 evolution was primarily driven by tobacco signatures (SBS4). Conversely, Group 2 exhibited late-stage acquisition of a DNA mismatch repair deficiency (MMRd) signature (SBS15), fueling trace subclonal diversification. Clinically, Group 2 demonstrated a significantly lower objective response rate (ORR) to platinum-based regimens (25.0% vs. 81.3%, P=0.02). Furthermore, the Subclonal-rich architecture independently predicted inferior overall survival (OS) [adjusted hazard ratio (adj. HR) =2.93, P=0.02], driven predominantly by limited-stage disease. Cross-cancer analysis validated this histology-dependent, high-heterogeneity adverse pattern in early-stage LUSC but not in LUAD. CONCLUSIONS: This hypothesis-generating study demonstrates that a "Subclonal-rich" architecture, driven by acquired MMRd, identifies high-risk, chemo-resistant SCLC. Our GMM approach suggests that pre-existing heterogeneity may serve as a potential, histology-dependent prognostic marker that warrants prospective validation for tailoring future therapeutic regimens.

Gaussian Mixture Model (GMM)↗
PubMed2025

Diversification, loss, and virulence gains of the major effector AvrStb6 during continental spread of the wheat pathogen Zymoseptoria tritici.

Interactions between plant pathogens and their hosts are highly dynamic and mainly driven by pathogen effectors and plant receptors. Host-pathogen co-evolution can cause rapid diversification or loss of pathogen genes encoding host-exposed proteins. The molecular mechanisms that underpin such sequence dynamics remains poorly investigated at the scale of entire pathogen species. Here, we focus on AvrStb6, a major effector of the global wheat pathogen Zymoseptoria tritici, evolving in response to the cognate receptor Stb6, a resistance widely deployed in wheat. We comprehensively captured effector gene evolution by analyzing a global thousand-genome panel using reference-free sequence analyses. We found that AvrStb6 has diversified into 59 protein isoforms with a strong association to the pathogen spreading to new continents. Across Europe, we found the strongest differentiation of the effector consistent with high rates of Stb6 deployment. The AvrStb6 locus showed also a remarkable diversification in transposable element content with specific expansion patterns across the globe. We detected AvrStb6 gene losses and evidence for transposable element-mediated disruptions. We used virulence datasets of genome-wide association mapping studies to predict virulence changes across the global panel. Genomic predictions suggested marked increases in virulence on Stb6 cultivars concomitant with the spread of the pathogen to Europe and the subsequent spread to further continents. Finally, we genotyped French bread wheat cultivars for Stb6 and monitored resistant cultivar deployment concomitant with AvrStb6 evolution. Taken together, our data provides a comprehensive view of how a rapidly diversifying effector locus can undergo large-scale sequence changes concomitant with gains in virulence on resistant cultivars. The analyses highlight also the need for large-scale pathogen sequencing panels to assess the durability of resistance genes and improve the sustainability of deployment strategies.

Ascomycota↗
PubMed1990

Independent gene evolution in the potato actin gene family demonstrated by phylogenetic procedures for resolving gene conversions and the phylogeny of angiosperm actin genes.

Nine different actin DNA sequences were isolated from the common potato, Solanum tuberosum, and the nucleotide sequence of five actin loci and of two allelic variants are presented. Unlike the wide variation in intron position among animal actin genes, the potato actin genes have three introns situated in the same positions as reported for all other angiosperm actin genes. Using a novel combination of analytical procedures (G-test and compatibility analysis), we could not find evidence of frequent large or small nonreciprocal exchanges of genetic material between the sequenced loci, although there were a few candidates. Resolution of such gene conversion events and the quantification of independence of gene evolution in multigene families is critical to the inference of phylogenetic relationships. Comparison with actin genes in other angiosperm species suggests that the actin multigene family can be divided into a number of subfamilies, evolved by descent rather than gene conversion, which are of possible functional origin, with one major subfamily diversification occurring before the divergence of monocots and dicots. The silent rate of nucleotide substitution was estimated to be similar to that suggested for a number of other plant nuclear genes, whereas the replacement rate was extremely slow, suggestive of selective constraints.

Actins↗
PubMedDate not supplied

Considering a diabetes management company.

In today's cost-conscious environment, outside management services are increasingly becoming integrated components of a hospital's overall structure and diversification strategy. Diabetes patients represent a significant percentage of hospital admission rates and market share; correspondingly, hospitals are initiating diabetes product lines to attain a leadership position in diabetes treatment. A management firm specializing in diabetes may offer significant advantages over in-house program development. A careful analysis of the company and its product will help identify a quality service that can meet both the needs of the hospital and the community it serves. Diabetes educators can play an important role in determining the need and feasibility of a managed service and in the evaluation of competing diabetes management firms.

Diabetes Mellitus↗