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PubMed2004

Towards a continuous evolution and adaptation of information systems in healthcare.

OBJECTIVES: To address the problem of alignment of health information systems to healthcare processes, which is a major challenge in healthcare organizations; to present a layered approach for system evolution and adaptation based on an application framework and rapid application development; to accomplish a demand-driven system evolution by embedding the software engineering process in business process optimization projects and by closely involving end users to improve their own work practices. METHODS: We have used a holistic health information system as a core application framework. System functionality is incrementally improved using an integrated "generator tool" for rapid application development. We have developed an iterative and participatory software engineering process, adapted to the conditions of the generator tool. The documentation techniques provided by the Unified Modeling Language (UML) were modified to achieve a straight forward documentation covering the whole development cycle from the business process model to generator-based computer applications. RESULTS AND CONCLUSION: The layered approach for system evolution did provide an environment in which a flexible and participatory software development process could be established. Today, generator-based applications are used in all clinical departments of our 1200-bed University Hospital. We expect that tools for rapid application development will be further improved and will play an increasingly important role to establish responsive IT-infrastructures where the application developer can concentrate on business process alignment instead of coding and debugging.

Academic Medical Centers↗
PubMed2025

Genomic insights into karyotype evolution and adaptive mechanisms in Polygonaceae species.

Polygonaceae, with ecological versatility and global distribution, is an ideal system for investigating plant adaptation. However, the genomic mechanisms underlying its karyotype evolution and environmental resilience remain unclear. We herein present chromosome-level genomes of 11 species from 10 Polygonaceae genera. Our analyses reveal that Gypsy retrotransposons are key drivers of genome size variations in Polygonaceae. We reconstructed a Polygonaceae ancestral karyotype comprising 28 proto-chromosomes and elucidated evolutionary trajectories via extensive chromosomal rearrangements. Furthermore, we constructed a cross-genus super pan-genome for Polygonaceae, identifying 80,055 gene families, of which 9,845 (12.30%) are core gene families. Private genes are found to contribute significantly to interspecific differences in adaptability. Notably, gene copy number variations are identified as a critical factor influencing adaptations to diverse niches involving species-specific increases in metabolic pathways. This study provides a genomic framework for Polygonaceae karyotype plasticity and adaptive innovation, offering insights into plant evolution under environmental challenges.

Karyotype↗
PubMedDate not supplied

New directions in comparative physiology and biochemistry: mechanisms, adaptations, and evolution.

Historically, the discipline of comparative physiology and biochemistry has had two major goals: (1) elucidation of mechanisms and their adaptative significance, and (2) understanding of the evolution of mechanisms and adaptations. In general, the first goal has dominated the field. In a mechanistic/adaptational approach, the diversity of organisms is an experimental parameter in the investigation. Lineage-specific characteristics reveal both how physiological systems work and how different kinds of animals are adapted to different kinds of environments. We believe that this approach is far from outdated, in part because many animal groups have been investigated superficially if at all, and in part because the incorporation of fundamentally new technologies into our discipline permits us to address previously intractable questions about even intensively studied animal groups. In evolutionary physiology and biochemistry, the diversity of lineage-specific physiological systems and how they came to be is the subject of investigation. Early attempts to employ the evolutionary approach were not only few in number, they were unsatisfying in outcome because neither phylogenetic nor mechanistic/adaptational knowledge was adequate to serve as a firm foundation. We agree with earlier authors that new and more sophisticated applications of this approach, together with progress in understanding both animal phylogeny and mechanisms/adaptations, all promise to allow us at last to fulfill our second historic goal. In our view, an integration of the two approaches seems to present the most productive trajectory into the next century.

Adaptation, Physiological↗
PubMed2005

Adaptive molecular evolution for 13,000 phage generations: a possible arms race.

Bacteriophage phiX174 was evolved on a continuous supply of sensitive hosts for 180 days ( approximately 13,000 phage generations). The average rate of nucleotide substitution was nearly 0.2% (11 substitutions)/20 days, and, surprisingly, substitutions accumulated in a clock-like manner throughout the study, except for a low rate during the first 20 days. Rates of silent and missense substitutions varied over time and among genes. Approximately 40% of the 71 missense changes and 25% of the 58 silent changes have been observed in previous adaptations; the rate of parallel substitution was highest in the early phase of the evolution, but 7% of the later changes had evolved in previous studies of much shorter duration. Several lines of evidence suggest that most of the changes were adaptive, even many of the silent substitutions. The sustained, high rate of adaptive evolution for 180 days defies a model of adaptation to a constant environment. We instead suggest that continuing molecular evolution reflects a potentially indefinite arms race, stemming from high levels of co-infection and the resulting conflict among genomes competing within the same cell.

Adaptation, Biological↗
PubMed1999

Evolution by small steps and rugged landscapes in the RNA virus phi6.

Fisher's geometric model of adaptive evolution argues that adaptive evolution should generally result from the substitution of many mutations of small effect because advantageous mutations of small effect should be more common than those of large effect. However, evidence for both evolution by small steps and for Fisher's model has been mixed. Here we report supporting results from a new experimental test of the model. We subjected the bacteriophage phi6 to intensified genetic drift in small populations and caused viral fitness to decline through the accumulation of a deleterious mutation. We then propagated the mutated virus at a range of larger population sizes and allowed fitness to recover by natural selection. Although fitness declined in one large step, it was usually recovered in smaller steps. More importantly, step size during recovery was smaller with decreasing size of the recovery population. These results confirm Fisher's main prediction that advantageous mutations of small effect should be more common. We also show that the advantageous mutations of small effect are compensatory mutations whose advantage is conditional (epistatic) on the presence of the deleterious mutation, in which case the adaptive landscape of phi6 is likely to be very rugged.

Bacteriophage phi 6↗
PubMed2001

Completely derandomized self-adaptation in evolution strategies.

This paper puts forward two useful methods for self-adaptation of the mutation distribution - the concepts of derandomization and cumulation. Principle shortcomings of the concept of mutative strategy parameter control and two levels of derandomization are reviewed. Basic demands on the self-adaptation of arbitrary (normal) mutation distributions are developed. Applying arbitrary, normal mutation distributions is equivalent to applying a general, linear problem encoding. The underlying objective of mutative strategy parameter control is roughly to favor previously selected mutation steps in the future. If this objective is pursued rigorously, a completely derandomized self-adaptation scheme results, which adapts arbitrary normal mutation distributions. This scheme, called covariance matrix adaptation (CMA), meets the previously stated demands. It can still be considerably improved by cumulation - utilizing an evolution path rather than single search steps. Simulations on various test functions reveal local and global search properties of the evolution strategy with and without covariance matrix adaptation. Their performances are comparable only on perfectly scaled functions. On badly scaled, non-separable functions usually a speed up factor of several orders of magnitude is observed. On moderately mis-scaled functions a speed up factor of three to ten can be expected.

Algorithms↗
PubMed2005

Adaptive molecular evolution in the opsin genes of rapidly speciating cichlid species.

Cichlid fish inhabit a diverse range of environments that vary in the spectral content of light available for vision. These differences should result in adaptive selective pressure on the genes involved in visual sensitivity, the opsin genes. This study examines the evidence for differential adaptive molecular evolution in East African cichlid opsin genes due to gross differences in environmental light conditions. First, we characterize the selective regime experienced by cichlid opsin genes using a likelihood ratio test format, comparing likelihood models with different constraints on the relative rates of amino acid substitution, across sites. Second, we compare turbid and clear lineages to determine if there is evidence of differences in relative rates of substitution. Third, we present evidence of functional diversification and its relationship to the photic environment among cichlid opsin genes. We report statistical evidence of positive selection in all cichlid opsin genes, except short wavelength-sensitive 1 and short wavelength-sensitive 2b. In all genes predicted to be under positive selection, except short wavelength-sensitive 2a, we find differences in selective pressure between turbid and clear lineages. Potential spectral tuning sites are variable among all cichlid opsin genes; however, patterns of substitution consistent with photic environment-driven evolution of opsin genes are observed only for short wavelength-sensitive 1 opsin genes. This study identifies a number of promising candidate-tuning sites for future study by site-directed mutagenesis. This work also begins to demonstrate the molecular evolutionary dynamics of cichlid visual sensitivity and its relationship to the photic environment.

Animals↗
PubMed1984

Phytoalexins and disease resistance mechanisms from a perspective of evolution and adaptation.

Plants respond to cellular injury and infection by accumulating low molecular weight antimicrobial stress metabolites called phytoalexins. The accumulation of phytoalexins, together with lignification, suberization, callose formation and the production of agglutinins and inhibitors of extracellular microbial hydrolases, appears to be part of a multi-component response mechanism associated with disease resistance and wound repair. Compared to the antibody-antigen response in animals, the phytoalexin response in plants has low specificity for induction and activity of the phytoalexins. Plants also contain preformed antimicrobial chemical and physical barriers to infection in their external tissues. The successful pathogen has evolved to cope with preformed inhibitors and barriers and either avoids eliciting the response mechanism, or suppresses the mechanism, or detoxifies its antimicrobial components. Annual plants can be systemically immunized against diseases caused by viruses, bacteria and fungi by limited infection with any one of the respective organisms. As with animals, disease resistance in plants depends on the rate and magnitude of response rather than on the ability to respond. The genetic information for disease resistance is found in all organisms, and disease resistance is the rule in nature. The interactions of plants with microorganisms in their environment are nature's example of diplomacy--compromise, adjustment to change and avoidance of deadly conflict.

Adaptation, Biological↗
PubMed2000

Extensive amino acid polymorphism at the pgm locus is consistent with adaptive protein evolution in Drosophila melanogaster.

PGM plays a central role in the glycolytic pathway at the branch point leading to glycogen metabolism and is highly polymorphic in allozyme studies of many species. We have characterized the nucleotide diversity across the Pgm gene in Drosophila melanogaster and D. simulans to investigate the role that protein polymorphism plays at this crucial metabolic branch point shared with several other enzymes. Although D. melanogaster and D. simulans share common allozyme mobility alleles, we find these allozymes are the result of many different amino acid changes at the nucleotide level. In addition, specific allozyme classes within species contain several amino acid changes, which may explain the absence of latitudinal clines for PGM allozyme alleles, the lack of association of PGM allozymes with the cosmopolitan In(3L)P inversion, and the failure to detect differences between PGM allozymes in functional studies. We find a significant excess of amino acid polymorphisms within D. melanogaster when compared to the complete absence of fixed replacements with D. simulans. There is also strong linkage disequilibrium across the 2354 bp of the Pgm locus, which may be explained by a specific amino acid haplotype that is high in frequency yet contains an excess of singleton polymorphisms. Like G6pd, Pgm shows strong evidence for a branch point enzyme that exhibits adaptive protein evolution.

Adaptation, Physiological↗
PubMed1998

Molecular evidence for parallel evolution of adaptive syndromes in fig-breeding Lissocephala (Drosophilidae).

Afrotropical Lissocephala (Drosophilidae) breed strictly in syconia (figs) of Ficus (Moraceae) and have accordingly evolved specific features including modified female and eggshell morphologies, ovipositing, larval foraging, and mating behaviors. These various traits may exist as two or three alternative states. Each species displays a specific suite of traits so closely coordinated with one another that alternative states of the overall suites of traits can be seen as "adaptive syndromes." Three clear-cut adaptive syndromes can be recognized while two taxonomic lineages (juncta and sanu species groups) are traditionally accepted on the basis of male terminalia. A crucial evolutionary question results from the consideration that ecological clusters and taxonomic groups have conflicting compositions: the three syndromes are found in the juncta group while two of them occur in the sanu group. To resolve this conflict, we present molecular data which provide a robust phylogeny: mitochondrial DNA (12S + 16S ribosomal DNA and cytochrome b) sequence data are in agreement with one another regardless of the algorithm used. All molecular data consistently support male terminalia dichotomy. Such a level of consistency unambiguously indicates that parallel evolution of adaptive syndromes occurred. Thus, homoplasy may affect morphological and behavioral traits concomitantly when these are involved in a network of functional relationships.

Adaptation, Physiological↗
PubMed2026

A pangenome framework uncovers the role of deletions in repeated evolution of cave-derived traits.

Structural variants (SVs) are increasingly recognized as key contributors to adaptive evolution, yet they remain underexplored compared with single-nucleotide variation. To understand how large-scale genomic changes shape repeated evolution, we leveraged multiple levels of sequence data across the powerful evolutionary model system of the Mexican tetra fish (Astyanax mexicanus). We constructed one of the first pangenome graphs from a naturally evolving vertebrate, enabling comprehensive discovery of SVs among 120 fish from 11 populations. We discover substantial amounts of structural variation and explore the roles of genomic biases and selection in shaping the distribution of these variants. More than 2400 high-confidence cave-specific deletions are enriched in biological pathways involved in vision, metabolism, and behavior and cluster nonrandomly in quantitative trait loci linked to cavefish traits. Additionally, 67 genes harbor unique deletions between independent cavefish lineages. These reused genes show evidence of population-specific selection (99% contain selective sweeps compared with 8%-15% in genes lacking SVs), indicating that deletions likely rose in frequency through repeated positive selection rather than drift. Together, these results reveal that recurrent deletion events have repeatedly contributed to the evolution of cave-adapted phenotypes and highlight deletions as underexplored contributors of adaptive evolution in extreme environments.

Animals↗
PubMed2026

Adaptive laboratory evolution enables carbon-negative mixotrophic fermentation and enhanced chain elongation in Clostridium sp. JS66.

Improving carbon recovery during sugar fermentation remains a major challenge because a substantial fraction of substrate carbon is lost as CO2 during central metabolism. To overcome this limitation, Clostridium sp. JS66 (JS66), an acetogen producing hexanoic acid from glucose, was subjected to adaptive laboratory evolution under autotrophic CO2/H2 conditions to enhance H2-assisted CO2 reassimilation during glucose fermentation. The evolved strain, ALECO2, exhibited CO2 consumption without a lag phase under autotrophic conditions and reached a 9.5-fold higher CO2 uptake rate than JS66. Under fed-batch mixotrophic conditions, glucose-only fermentation yielded a carbon molar yield (Cmetabolite/Csugar, CM/CS) of 0.60, whereas H2 supplementation increased CM/CS to 0.91 and redirected carbon flux toward C6 products (hexanoic acid and hexanol), which accounted for 49% of total C_output. With additional CO2 supplementation, ALECO2 further assimilated externally supplied CO2, increasing the CM/CS to 1.10 and demonstrating carbon-negative fermentation. Assimilation of externally supplied CO2 further redirected carbon flux toward chain elongation, producing 7.14 g/L hexanoic acid and increasing the C6 carbon fraction to 57% of total C_output. Constraint-based flux analysis supported increased acetyl-CoA formation through the Wood-Ljungdahl pathway and enhanced flux toward reverse β-oxidation under H2- and CO2/H2-supplemented conditions. Genome analysis identified mutations including genes encoding a putative HytB homolog and a LysR-type transcriptional regulator. These results establish ALECO2 as a promising evolved anaerobic non-photosynthetic (ANP) mixotrophy platform that links CO2 reassimilation and external CO2 assimilation with chain elongation, enabling carbon-neutral and carbon-negative production of value-added C6 products from glucose.

Anaerobic non-photosyntheticmixotrophy (ANP)↗
PubMed2006

Adaptive protein evolution and regulatory divergence in Drosophila.

Two recent studies demonstrated a positive correlation between divergence in gene expression and protein sequence in Drosophila. This correlation could be driven by positive selection or variation in functional constraint. To distinguish between these alternatives, we compared patterns of molecular evolution for 1,862 genes with two previously reported estimates of expression divergence in Drosophila. We found a slight negative trend (nonsignificant) between positive selection on protein sequence and divergence in expression levels between Drosophila melanogaster and Drosophila simulans. Conversely, shifts in expression patterns during Drosophila development showed a positive association with adaptive protein evolution, though as before the relationship was weak and not significant. Overall, we found no strong evidence for an increase in the incidence of positive selection on protein-coding regions in genes with divergent expression in Drosophila, suggesting that the previously reported positive association between protein and regulatory divergence primarily reflects variation in functional constraint.

Amino Acid Sequence↗
PubMed2006

Positive selection on the nonhomologous end-joining factor Cernunnos-XLF in the human lineage.

BACKGROUND: Cernunnos-XLF is a nonhomologous end-joining factor that is mutated in patients with a rare immunodeficiency with microcephaly. Several other microcephaly-associated genes such as ASPM and microcephalin experienced recent adaptive evolution apparently linked to brain size expansion in humans. In this study we investigated whether Cernunnos-XLF experienced similar positive selection during human evolution. RESULTS: We obtained or reconstructed full-length coding sequences of chimpanzee, rhesus macaque, canine, and bovine Cernunnos-XLF orthologs from sequence databases and sequence trace archives. Comparison of coding sequences revealed an excess of nonsynonymous substitutions consistent with positive selection on Cernunnos-XLF in the human lineage. The hotspots of adaptive evolution are concentrated around a specific structural domain, whose analogue in the structurally similar XRCC4 protein is involved in binding of another nonhomologous end-joining factor, DNA ligase IV. CONCLUSION: Cernunnos-XLF is a microcephaly-associated locus newly identified to be under adaptive evolution in humans, and possibly played a role in human brain expansion. We speculate that Cernunnos-XLF may have contributed to the increased number of brain cells in humans by efficient double strand break repair, which helps to prevent frequent apoptosis of neuronal progenitors and aids mitotic cell cycle progression. REVIEWERS: This article was reviewed by Chris Ponting and Richard Emes (nominated by Chris Ponting), Kateryna Makova, Gáspár Jékely and Eugene V. Koonin.

Journal Article↗
PubMed2006

Genetics, development and evolution of adaptive pigmentation in vertebrates.

The study of pigmentation has played an important role in the intersection of evolution, genetics, and developmental biology. Pigmentation's utility as a visible phenotypic marker has resulted in over 100 years of intense study of coat color mutations in laboratory mice, thereby creating an impressive list of candidate genes and an understanding of the developmental mechanisms responsible for the phenotypic effects. Variation in color and pigment patterning has also served as the focus of many classic studies of naturally occurring phenotypic variation in a wide variety of vertebrates, providing some of the most compelling cases for parallel and convergent evolution. Thus, the pigmentation model system holds much promise for understanding the nature of adaptation by linking genetic changes to variation in fitness-related traits. Here, I first discuss the historical role of pigmentation in genetics, development and evolutionary biology. I then discuss recent empirically based studies in vertebrates, which rely on these historical foundations to make connections between genotype and phenotype for ecologically important pigmentation traits. These studies provide insight into the evolutionary process by uncovering the genetic basis of adaptive traits and addressing such long-standing questions in evolutionary biology as (1) are adaptive changes predominantly caused by mutations in regulatory regions or coding regions? (2) is adaptation driven by the fixation of dominant mutations? and (3) to what extent are parallel phenotypic changes caused by similar genetic changes? It is clear that coloration has much to teach us about the molecular basis of organismal diversity, adaptation and the evolutionary process.

Adaptation, Biological↗