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Results for “evolutionary potentiation”

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PubMed2003

Effect of ribavirin and amantadine on early hepatitis C virus RNA rebound and clearance in serum during daily high-dose interferon.

The early rebound in serum HCV RNA during HCV dynamic studies with high-dose interferon may be due to de novo infection with interferon escape quasispecies. We simultaneously measured serum alanine aminotransferase (ALT) and HCV RNA at rapid intervals in chronic HCV liver disease patients during interferon therapy alone or in combination with ribavirin and amantadine. HCV RNA declined rapidly between 0 and 48 hr in all patients (phase 1). Ribavirin and amantadine significantly increased this phase 1 decline. In all four monotherapy patients with viral rebound, the increasing levels of HCV RNA were associated with a parallel increase in serum ALT, consistent with a hepatitis flare or de novo infection. By contrast, in the four monotherapy patients without viral rebound, and all eight patients receiving combination therapy, the slow progressive phase two decay was associated with declining serum ALT levels. Ribavirin or ribavirin and amantadine significantly and incrementally increased the phase two HCV RNA clearance. Dynamic sequencing in the HVR1 region in one rebound patient confirmed the potential for rapid evolutionary changes during interferon therapy. These preliminary data suggest that early viral rebound might be associated with de novo infection with interferon escape HCV variants, which in turn are attenuated by ribavirin and amantadine.

Adult↗
PubMed2003

Allele frequency and genotype distribution of polymorphisms within disease-related genes is influenced by ethnic population sub-structuring in Sudan.

Four single nucleotide polymorphisms (SNPs) and a variable number of tandem repeats (VNTR) polymorphism located within disease associated/causing genes were typed in four populations of different tribal and ethnic affiliation from the Sudan. The genotype and allele frequencies were compared with those of other groups from published and unpublished data of world populations. The combined Sudanese sample conformed with Hardy-Weinberg equilibrium (HWE) expectation. However, population sub-structuring according to ethnic/linguistic group indicated at least two SNPs in departure from HWE. Differences in allele frequencies and genotype distribution between groups was also noted in three of the four SNPs. The other loci were distributed homogeneously within the populations studied with genotype frequencies in agreement with HWE expectation. These results highlight the importance of inter-population stratification for polymorphic markers, as well as the potential influence of evolutionary history and ethnic variation of loci, in the general distribution of SNPs and other polymorphisms.

Evolution, Molecular↗
PubMed2002

Sex releases the speed limit on evolution.

Explaining the evolutionary maintenance of sex remains a key problem in evolutionary biology. One potential benefit of sex is that it may allow a more rapid adaptive response when environmental conditions change, by increasing the efficiency with which selection can fix beneficial mutations. Here I show that sex can increase the rate of adaptation in the facultatively sexual single-celled chlorophyte Chlamydomonas reinhardtii, but that the benefits of sex depend crucially on the size of the population that is adapting: sex has a marked effect in large populations but little effect in small populations. Several mechanisms have been proposed to explain the benefits of sex in a novel environment, including stochastic effects in small populations, clonal interference and epistasis between beneficial alleles. These results indicate that clonal interference is important in this system.

Adaptation, Physiological↗
PubMed2025

Design of highly functional genome editors by modelling CRISPR-Cas sequences.

Gene editing has the potential to solve fundamental challenges in agriculture, biotechnology and human health. CRISPR-based gene editors derived from microorganisms, although powerful, often show notable functional tradeoffs when ported into non-native environments, such as human cells1. Artificial-intelligence-enabled design provides a powerful alternative with the potential to bypass evolutionary constraints and generate editors with optimal properties. Here, using large language models2 trained on biological diversity at scale, we demonstrate successful precision editing of the human genome with a programmable gene editor designed with artificial intelligence. To achieve this goal, we curated a dataset of more than 1 million CRISPR operons through systematic mining of 26 terabases of assembled genomes and metagenomes. We demonstrate the capacity of our models by generating 4.8× the number of protein clusters across CRISPR-Cas families found in nature and tailoring single-guide RNA sequences for Cas9-like effector proteins. Several of the generated gene editors show comparable or improved activity and specificity relative to SpCas9, the prototypical gene editing effector, while being 400 mutations away in sequence. Finally, we demonstrate that an artificial-intelligence-generated gene editor, denoted as OpenCRISPR-1, exhibits compatibility with base editing. We release OpenCRISPR-1 to facilitate broad, ethical use across research and commercial applications.

CRISPR-Cas Systems↗
PubMed2005

Modular evolution of egg case silk genes across orb-weaving spider superfamilies.

Spider silk proteins (fibroins) are renowned for their extraordinary mechanical properties and biomimetic potential. Despite extensive evolutionary, ecological, and industrial interest in these fibroins, only a fraction of the known silk types have been characterized at the molecular level. Here we report cDNA and genomic sequences of the fibroin TuSp1, which appears to be the major component of tubuliform gland silk, a fiber exclusively synthesized by female spiders for egg case construction. We obtained TuSp1 sequences from 12 spider species that represent the extremes of phylogenetic diversity within the Orbicularia (orb-weaver superfamilies, Araneoidea and Deinopoidea) and finer scale sampling within genera. TuSp1 encodes tandem arrays of an approximately 200-aa-long repeat unit and individual repeats are readily aligned, even among species that diverged >125 million years ago. Analyses of these repeats across species reveal the strong influence of concerted evolution, resulting in intragenic homogenization. However, deinopoid TuSp1 repeats also contain insertions of coding, minisatellite-like sequences, an apparent result of replication slippage and nonreciprocal recombination. Phylogenetic analyses of 37 spider fibroin sequences support the monophyly of TuSp1 within the spider fibroin gene family, consistent with a single origin of this ortholog group. The diversity of taxa and silks examined here confirms that repetitive architecture is a general feature of this gene family. Moreover, we show that TuSp1 provides a clear example of modular evolution across a range of phylogenetic levels.

Amino Acid Sequence↗
PubMed2002

Targeting the malarial plastid via the parasitophorous vacuole.

The malarial "apicoplast" derived from an algal plastid, has stimulated interest for its novel evolutionary biology and potential as a drug target. An endoplasmic reticulum-type signal sequence followed by a plastid targeting sequence are required to target proteins to the apicoplast but the pathway by which proteins are transported to the organelle is unknown. By stage regulating the expression of transgenes we show that early (0-12 h) in the parasite's development in red cells, newly synthesized green fluorescent protein that contains the plastid targeting sequence (plastid targeting sequence-green fluorescent protein (PTS-GFP)) is recruited into the parasite's secretory pathway. PTS-GFP in 0-12-h parasites is found released into the parasitophorous vacuole (PV) and in apposition with the Golgi. However, import into the apicoplast and processing to GFP does not occur until 18-36 h in development. In intermediate, 18-h parasites PTS-GFP resides in the PV. Quantitative exit of PTS-GFP from the PV and its conversion to GFP is seen at 36 h. The data suggest that: (i) import into the apicoplast is stage regulated and (ii) the PTS can signal endomembrane targeting from the PV to the apicoplast.

Animals↗
PubMed2002

Analyzing developmental sequences within a phylogenetic framework.

Heterochrony is important as a potential mechanism of evolutionary change. However, the analysis of developmental timing data within a phylogenetic framework to identify important shifts has proven difficult. In particular, analytical problems with sequence (event) heterochrony revolve around the lack of an absolute time frame in development to allow standardization of timing data across species. An important breakthrough in this regard is the method of "event-pairing," which compares the relative timing of developmental events in a pairwise fashion. The resulting event-pair-encoded data can be mapped onto a phylogeny, which can provide important biological information. However, event-paired data are cumbersome to work with and lack a rigorous quantitative framework under which to analyze them. Critically, the otherwise advantageous relativity of event-pairing prevents an assessment of whether one or both events in a single event-pair have changed position during evolutionary history. Building on the method of event-pairing, we describe a protocol whereby event-pair transformations along a given branch are analyzed en bloc. Our method of "event-pair cracking" thereby allows developmental timing data to be analyzed quantitatively within a phylogenetic framework to infer key heterochronic shifts. We demonstrate the utility of event-pair cracking through a worked example and show how it provides a set of desired features identified by previous authors.

Animals↗
PubMed2000

A sensitive denaturing gradient-Gel electrophoresis assay reveals a high frequency of heteroplasmy in hypervariable region 1 of the human mtDNA control region.

A population study of heteroplasmy in the hypervariable region 1 (HV1) portion of the human mtDNA control region was performed. Blood samples from 253 randomly chosen individuals were examined using a sensitive denaturing gradient-gel electrophoresis (DGGE) system. This method is capable of detecting heteroplasmic proportions as low as 1% and virtually all heteroplasmy where the minor component is > or = 5%. Heteroplasmy was observed in 35 individuals (13.8%; 95% confidence interval [CI] 9.6-18.0). Of these individuals, 33 were heteroplasmic at one nucleotide position, whereas 2 were heteroplasmic at two different positions (a condition known as "triplasmy"). Although heteroplasmy occurred at a total of 16 different positions throughout HV1, it was most frequently observed at positions 16093 (n=13) and 16129 (n=6). In addition, the majority of heteroplasmic variants occurred at low proportions and could not be detected by direct sequencing of PCR products. This study indicates that low-level heteroplasmy in HV1 is relatively common and that it occurs at a broad spectrum of sites. Our results corroborate those of other recent reports indicating that heteroplasmy in the control region is more common than was previously believed-a finding that is of potential importance to evolutionary studies and forensic applications that are based on mtDNA variation.

Base Sequence↗
PubMed2002

The ecology of individuals: incidence and implications of individual specialization.

Most empirical and theoretical studies of resource use and population dynamics treat conspecific individuals as ecologically equivalent. This simplification is only justified if interindividual niche variation is rare, weak, or has a trivial effect on ecological processes. This article reviews the incidence, degree, causes, and implications of individual-level niche variation to challenge these simplifications. Evidence for individual specialization is available for 93 species distributed across a broad range of taxonomic groups. Although few studies have quantified the degree to which individuals are specialized relative to their population, between-individual variation can sometimes comprise the majority of the population's niche width. The degree of individual specialization varies widely among species and among populations, reflecting a diverse array of physiological, behavioral, and ecological mechanisms that can generate intrapopulation variation. Finally, individual specialization has potentially important ecological, evolutionary, and conservation implications. Theory suggests that niche variation facilitates frequency-dependent interactions that can profoundly affect the population's stability, the amount of intraspecific competition, fitness-function shapes, and the population's capacity to diversify and speciate rapidly. Our collection of case studies suggests that individual specialization is a widespread but underappreciated phenomenon that poses many important but unanswered questions.

Animals↗
PubMed2005

Predation risk influences adaptive morphological variation in fish populations.

Predators can cause a shift in both density and frequency of a prey phenotype that may lead to phenotypic divergence through natural selection. What is less investigated is that predators have a variety of indirect effects on prey that could potentially have large evolutionary responses. We conducted a pond experiment to test whether differences in predation risk in different habitats caused shifts in behavior of prey that, in turn, would affect their morphology. We also tested whether the experimental data could explain the morphological variation of perch in the natural environment. In the experiment, predators caused the prey fish to shift to the habitat with the lower predation risk. The prey specialized on habitat-specific resources, and there was a strong correlation between diet of the prey fish and morphological variation, suggesting that resource specialization ultimately affected the morphology. The lack of differences in competition and mortality suggest that the morphological variation among prey was induced by differences in predation risk among habitats. The field study demonstrated that there are differences in growth related to morphology of perch in two different habitats. Thus, a trade-off between foraging and predator avoidance could be responsible for adaptive morphological variation of young perch.

Adaptation, Physiological↗
PubMed2003

In vitro evolution of proteins for drug development.

Thanks to biotechnology, proteins are becoming increasingly important tools to fight disease, both as therapeutics in their own right and as catalysts for the synthesis of small molecule drugs. However, the properties of these proteins are not necessarily optimal for their intended tasks. In vitro evolution is a set of technologies useful to address their shortcomings. Moreover, in vitro evolution can help illuminate natural evolutionary pathways, thus potentially enabling prediction of drug resistance evolution. We consider here recent developments in the area of in vitro evolution, as well as its application to proteins of interest to medical science.

Biological Assay↗
PubMed2006

Functional coordination between leaf gas exchange and vulnerability to xylem cavitation in temperate forest trees.

We examined functional coordination among stem and root vulnerability to xylem cavitation, plant water transport characteristics and leaf traits in 14 co-occurring temperate tree species. Relationships were evaluated using both traditional cross-species correlations and phylogenetically independent contrast (PIC) correlations. For stems, the xylem tension at which 50% of hydraulic conductivity was lost (psi50) was positively associated (P < 0.001) with specific conductivity (K(S)) and with mean hydraulically weighted xylem conduit diameter (D(h-w)), but was only marginally (P = 0.06) associated with leaf specific conductivity (K(L)). The PIC correlation for each of these relationships, however, was not statistically significant. There was also no relationship between root psi50 and root K(S) in either cross-species or PIC analysis. Photosynthetic rate (A) and stomatal conductance (g(s)) were strongly and positively correlated with root psi50 in the cross-species analysis (P < 0.001), a relationship that was robust to phylogenetic correction (P < 0.01). A and g(s) were also positively correlated with stem psi50 in the cross-species analysis (P = 0.02 and 0.10, respectively). However, only A was associated with stem psi50 in the PIC analysis (P = 0.04). Although the relationship between vulnerability to cavitation and xylem conductivity traits within specific organs (i.e. stems and roots) was weak, the strong correlation between g(s) and root psi50 across species suggests that there is a trade-off between vulnerability to cavitation and water transport capacity at the whole-plant level. Our results were therefore consistent with the expectation of coordination between vulnerability to xylem cavitation and the regulation of stomatal conductance, and highlight the potential physiological and evolutionary significance of root hydraulic properties in controlling interspecific variation in leaf function.

Biological Transport↗
PubMed2004

Variation in natural selection for growth and phlorotannins in the brown alga Fucus vesiculosus.

Directional selection for plant traits associated with resistance to herbivory tends to eliminate genetic variation in such traits. On the other hand, balancing selection arising from trade-offs between resistance and growth or spatially variable selection acts against the elimination of genetic variation. We explore both the amount of genetic variation and variability of natural selection for growth and concentration of phenolic secondary compounds, phlorotannins, in the brown alga Fucus vesiculosus. We measured variation in selection at two growing depths and two levels of nutrient availability in algae that had faced two kinds of past growing environments. Genetic variation was low for growth but high for phlorotannins. The form and strength of selection for both focal traits depended on the past growing environment of the algae. We found strong directional selection for growth rate in algae previously subjected to higher ultraviolet radiation, but not in algae previously subjected to higher nutrient availability. Stabilizing selection for growth occurred especially in the deep growing environment. Selection for phlorotannins was generally weak, but in some past-environment-current-environment combinations we detected either directional selection against phlorotannins or stabilizing selection. Thus, phlorotannins are not selectively neutral but affect the fitness of F. vesiculosus. In particular, there may be a fitness cost of producing phlorotannins, but the realization of such a cost varies from one environment to another. Genetic correlations between selective environments were high for growth but nonexistent for phlorotannins, emphasizing the high phenotypic plasticity of phlorotannin production. The highly heterogeneous selection, including directional, stabilizing, and spatially variable selection as well as temporal change in selection due to responses to past environmental conditions, probably maintains a high amount of genetic variation in phlorotannins. Such variation provides the potential for rapid evolutionary response of phlorotannins under directional selection.

Analysis of Variance↗
PubMed2026

From isolation to insights: mitochondrial complex I in the diatom Phaeodactylum tricornutum.

Diatoms are among the most ecologically successful microalgae, contributing significantly to marine primary production and global carbon cycling. Their distinctive metabolic architecture, shaped by a complex evolutionary history involving secondary endosymbiosis, includes a highly compartmentalized cell organization and unique metabolic pathways. In Phaeodactylum tricornutum, a model pennate diatom, chloroplasts with four membranes and mitochondria of likely exosymbiotic origin exhibit intricate physical and metabolic interactions that support integrated carbon and nitrogen metabolism. The mitochondrial electron transport chain, essential for ATP synthesis, shows clade-specific structural and compositional adaptations. Despite its importance, detailed proteomic characterization has remained limited. Here, we report a method for the isolation of mitochondrial complex I from P. tricornutum and present a comprehensive proteomic analysis. Our results confirm the presence of carbonic anhydrase and bridge modules, both previously proposed as ancestral features of mitochondrial complex I, and identify at least one novel, clade-specific subunit that resembles NAD(P)H-dependent trans-2-enoyl-CoA/ACP reductases (TER) from other species. The subunit is similar to proteins involved in mitochondrial fatty acid biosynthesis. Our findings provide new insights into the composition, evolutionary conservation, and potential biotechnological relevance of this essential respiratory protein complex in diatoms.

Diatoms↗
PubMed1990

Viable endospores of Thermoactinomyces vulgaris in lake sediments as indicators of agricultural history.

Bacteria of the genus Thermoactinomyces form endospores with an extreme longevity in natural habitats. We isolated Thermoactinomyces sacchari from 9,000-year-old varved (annually laminated) sediment; thus, T. sacchari is probably one of the oldest known living organisms. More importantly, we tested and verified the hypothesis that there is a relationship between concentrations of dormant, viable endospores of T. vulgaris in lake sediments and the extent of agriculture in the catchments of the lakes. In surface sediments, low concentrations were recorded in forest lakes and the concentrations increased with increasing areas of cultivated land around the lakes. In varved sediment cores from three lakes, we found a temporal relationship between records of T. vulgaris endospores and the pollen of plants indicating agriculture. Endospores were very rare in sediments deposited before agriculture, ca. 1100 A.D. From then to between 1300 and 1700 A.D., a period with restricted cultivation, low but more regular rates of accumulation of endospores were recorded. High endospore accumulation rates were found with the subsequent agricultural expansion. This investigation confirms suggestions that this bacterium could be used as a paleoindicator for agricultural activity and be complementary to pollen analyses. Viable bacteria in continuous records of lake sediments are also potential material for evolutionary studies.

Agriculture↗
PubMed1983

Sequence repeats in a polyoma virus DNA region important for gene expression.

The sequenced prototype strains (A2 and A3) of polyoma virus lack sequence duplications characteristic of other papovaviruses. However, we found that five polyoma virus strains (P16, Toronto large plaque, MV, Ts 48, and NG59R) contain tandemly duplicated sequences in a region near the late RNA leader. Although the duplications vary in size (31 to 84 base pairs) and location (between nucleotide [nt] 5068 and nt 5185), the sequence between nt 5114 and nt 5137 is contained within all five duplicated segments. This region is known to be important in polyoma virus early gene expression, and it contains sequences capable of enhancing the expression of nonviral genes. Inspection of the sequences at and around the ends of the repeats indicated that the duplications do not arise by homologous recombination, and there was no indication that a sequence-specific mechanism results in their formation. However, the variation in the structure of the repeats among different polyoma virus strains suggests that these sequence duplications are a recent evolutionary occurrence. The potential biological significance of this variation is discussed.

Base Sequence↗
PubMed2025

A colorful legacy of hybridization in wood-warblers includes frequent sharing of carotenoid genes among species and genera.

Introgression between species has the potential to shape evolutionary trajectories in important ways, but uncovering complex introgression dynamics has only recently been made possible by advances in genomics. Warblers of the avian family Parulidae exemplify rapid diversification and sexual trait divergence, and we endeavored to study historical introgression in the family. We sequenced multiple genomes of nearly every species, constructed a phylogeny for the family, and investigated gene flow across the genome and at genes known for controlling feather color. We found that DNA haplotypes including the gene BCO2, which encodes an enzyme that degrades yellow carotenoids, have spread among genera multiple times-from Vermivora to Geothlypis and from Leiothlypis to multiple Cardellina and Setophaga species. Patterns of inheritance in the latter case point to introgression that occurred 0.5 to 2 million years ago, and the shared haplotype among recipient species is less than 100 nucleotides long. Separately, we found evidence of introgression from red Cardellina species to both of the two red Myioborus species at BDH1L and from one red Myioborus species to the other at CYP2J19; both are key genes in the pathway that converts yellow carotenoids to red ketocarotenoids. Our results show that introgression is a common mechanism for the evolution of colorful plumage in parulid warblers and hint at complex histories of gene flow behind some of the Western Hemisphere's most colorful birds.

Animals↗
PubMed2006

Nearly identical paralogs: implications for maize (Zea mays L.) genome evolution.

As an ancient segmental tetraploid, the maize (Zea mays L.) genome contains large numbers of paralogs that are expected to have diverged by a minimum of 10% over time. Nearly identical paralogs (NIPs) are defined as paralogous genes that exhibit > or = 98% identity. Sequence analyses of the "gene space" of the maize inbred line B73 genome, coupled with wet lab validation, have revealed that, conservatively, at least approximately 1% of maize genes have a NIP, a rate substantially higher than that in Arabidopsis. In most instances, both members of maize NIP pairs are expressed and are therefore at least potentially functional. Of evolutionary significance, members of many NIP families also exhibit differential expression. The finding that some families of maize NIPs are closely linked genetically while others are genetically unlinked is consistent with multiple modes of origin. NIPs provide a mechanism for the maize genome to circumvent the inherent limitation that diploid genomes can carry at most two "alleles" per "locus." As such, NIPs may have played important roles during the evolution and domestication of maize and may contribute to the success of long-term selection experiments in this important crop species.

Arabidopsis↗