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PubMed2005

Hybridization dynamics between sympatric species of trout: loss of reproductive isolation.

Although reinforcement should enhance reproductive barriers in sympatric species, sympatric trout species do hybridize. Using mitochondrial and nuclear species markers, we investigated hybridization directionality, hybrid mating biases, and selection against hybrids in 13 sympatric cut-throat and rainbow trout populations on Vancouver Island, Canada. Approximately 50% of the genotyped fish were hybrid (F1 or higher-order) and populations ranged from very recent (all F1 hybrids) to extremely advanced higher-order hybridization. Overall, interbreeding was reciprocal, although some populations showed directional hybridization. Pronounced cytonuclear disequilibrium in post-F1 hybrids indicated a remarkable mating bias not previously reported, which is most likely because of behavioural reproductive preferences. Selection against hybrids was observed in only two populations, indicative of extrinsic selection. Two populations were 'hybrid swarms', with a complete loss of reproductive isolation. The complex hybridization dynamics in this system represent a valuable natural experiment of the genetic and evolutionary implications of recent and on-going interspecific hybridization.

Animals↗
PubMed2026

Molecular dynamics simulations of positively selected codons in FcγRI reveal novel biochemical binding properties.

FcγRI is a high-affinity receptor for IgG, associated with autoimmune disease pathology and determines clinical responses to antibody-based immunotherapies. FcγRI has a complex evolutionary history that is not fully understood, and to address this we explored signatures of positive selection in the receptor's functional gene, FCGR1A, using codon-based selection tests on aligned 1-1 orthologous sequences from placental mammals (n = 32). Signatures of positive selection have occurred at several locations within the gene, with two sites (H148 (M2a ω 0.997 & M8 ω = 0.993)) and (W149 (M2a ω = 0.999 & M8 ω = 1.000)) exhibiting highest posterior probabilities, suggesting strong evidence of positive selection; these positions are known to form one of the FcγRI-IgG binding interfaces. We employed ancestral reconstruction to statistically infer prior codon sequences at these sites and identified ancestral H148P and W149R codons at different nodes in the phylogeny. Employing molecular dynamics simulations, we determined how evolutionary changes at these sites may have influenced the binding of FcγRI-IgG of modern-day Homo sapiens. Measuring RMSD, free energy, radius of gyration, hydrogen bond formation, and analyzing free energy landscapes, we demonstrate that structural instability between mutant structures vs the WT counterpart; however, overall binding potential increases at position 148, yet decreases at 149 in potential. H148P protonation at physiological pH remains similar, yet during acidotic calculations, protonation is likely reduced, with predicted reduction in affinity for IgG. While ancestral W149R substitutions demonstrate an implication for electron conjugation. Examining key sites at this binding FcγRI-IgG interface, our data demonstrate that these two codons have evolved in humans to be relatively insensitive to shifts in pH promoting a more stable interaction with the Fc portion of IgG during diseases that promote acidosis.

Receptors, IgG↗
PubMed2024

The physical and evolutionary energy landscapes of devolved protein sequences corresponding to pseudogenes.

Protein evolution is guided by structural, functional, and dynamical constraints ensuring organismal viability. Pseudogenes are genomic sequences identified in many eukaryotes that lack translational activity due to sequence degradation and thus over time have undergone "devolution." Previously pseudogenized genes sometimes regain their protein-coding function, suggesting they may still encode robust folding energy landscapes despite multiple mutations. We study both the physical folding landscapes of protein sequences corresponding to human pseudogenes using the Associative Memory, Water Mediated, Structure and Energy Model, and the evolutionary energy landscapes obtained using direct coupling analysis (DCA) on their parent protein families. We found that generally mutations that have occurred in pseudogene sequences have disrupted their native global network of stabilizing residue interactions, making it harder for them to fold if they were translated. In some cases, however, energetic frustration has apparently decreased when the functional constraints were removed. We analyzed this unexpected situation for Cyclophilin A, Profilin-1, and Small Ubiquitin-like Modifier 2 Protein. Our analysis reveals that when such mutations in the pseudogene ultimately stabilize folding, at the same time, they likely alter the pseudogenes' former biological activity, as estimated by DCA. We localize most of these stabilizing mutations generally to normally frustrated regions required for binding to other partners.

Cyclophilin A↗
PubMed2003

Structural dynamics of eukaryotic chromosome evolution.

Large-scale genome sequencing is providing a comprehensive view of the complex evolutionary forces that have shaped the structure of eukaryotic chromosomes. Comparative sequence analyses reveal patterns of apparently random rearrangement interspersed with regions of extraordinarily rapid, localized genome evolution. Numerous subtle rearrangements near centromeres, telomeres, duplications, and interspersed repeats suggest hotspots for eukaryotic chromosome evolution. This localized chromosomal instability may play a role in rapidly evolving lineage-specific gene families and in fostering large-scale changes in gene order. Computational algorithms that take into account these dynamic forces along with traditional models of chromosomal rearrangement show promise for reconstructing the natural history of eukaryotic chromosomes.

Animals↗
PubMed2004

Chaos and language.

Human language is a complex communication system with unlimited expressibility. Children spontaneously develop a native language by exposure to linguistic data from their speech community. Over historical time, languages change dramatically and unpredictably by accumulation of small changes and by interaction with other languages. We have previously developed a mathematical model for the acquisition and evolution of language in heterogeneous populations of speakers. This model is based on game dynamical equations with learning. Here, we show that simple examples of such equations can display complex limit cycles and chaos. Hence, language dynamical equations mimic complicated and unpredictable changes of languages over time. In terms of evolutionary game theory, we note that imperfect learning can induce chaotic switching among strict Nash equilibria.

Biological Evolution↗
PubMed2026

Deconstructing empirical fitness seascapes across scales of granularity.

The fitness landscape metaphor remains resonant in evolutionary theory and has facilitated the birth of newer concepts, like the fitness seascape, that consider the role of environmental context in shaping the dynamics of evolution. Since its emergence, the seascape has appeared in numerous studies examining how different and fluctuating environments shape evolutionary outcomes. Despite growing interest, we lack comprehensive examinations of how environmental context shapes features of fitness seascapes. In this study, we address this gap by deconstructing empirical fitness seascapes across scales of granularity: loci, locus interactions (epistasis), alleles, trajectories, and entire seascapes. For each, we examine how environmental context influences qualitative and quantitative aspects of seascapes, and find that they change appreciably, with patterns specific to individual systems of study. We also quantify how much each scale varies across environments, and find that certain scales tend to be more sensitive to context than others. In summary, we reflect on the implications of the seascape metaphor for the incorporation of environmental effects into theoretical population genetics, for understanding how the environment shapes evolution in disease systems, and for contemporary bioengineering efforts.

Genetic Fitness↗
PubMed2026

Stem Cell Differentiation Disperses Transcriptional Clusters via a Conserved Surface-Condensate Trajectory.

Stem cells exhibit exceptionally prominent transcriptional clusters, which dissolve with progressing differentiation. Although these clusters are assigned central roles in embryonic gene regulation, their formation and loss during differentiation remain poorly understood. This study reveals that these prominent clusters disperse along a conserved trajectory in mouse embryonic stem cells, fruit fly testes, and zebrafish embryos. Imaging and lattice simulations show that these clusters form via surface condensation on H3K27ac-marked super-enhancer regions, which act as genomic scaffolds. Upon differentiation, partial loss of these active epigenetic marks and transcription-driven unfolding lead to dispersal of the prominent clusters. The block copolymer-based lattice simulations explain this process as a conserved trajectory through a three-dimensional state space, governed by surface condensation principles that extend beyond canonical liquid-liquid phase separation. This work marks surface condensation as a biophysical mechanism for the dynamic organization of stem cell-specific transcriptional hubs and demonstrates evolutionary conservation in several organisms. By uncovering a conserved biophysical mechanism for transcriptional organization in development, our work illustrates how polymer properties can contribute to the control of cell identity and fate.

Animals↗
PubMed2007

Scopolamine in Brugmansia suaveolens (Solanaceae): defense, allocation, costs, and induced response.

Brugmansia suaveolens (Solanaceae) contains tropane alkaloids (TAs), which can act as chemical defenses. Selective pressures might modulate the allocation of alkaloids within the plant, as postulated by optimal-defense theory. By tracing scopolamine, the most abundant TA in this species, we found that scopolamine in an artificial diet, in concentrations similar to those in leaves of B. suaveolens, increased mortality and prolonged developmental time of the larvae of the generalist noctuid moth Spodoptera frugiperda. A diet of undamaged leaves of B. suaveolens also showed a large negative effect on the growth of larvae of S. frugiperda compared to a diet of leaves of Ricinus communis, a species that did not have negative effects on this moth; more valuable plant parts, such as young leaves, flowers, and unripe fruits with seeds, have higher scopolamine concentrations than other tissues; leaves of B. suaveolens increase their content of scopolamine after artificial damage. The highest induction was found 24 hr after the damage, and after that, scopolamine content decreased to constitutive levels. This increase represented a cost, because in another experiment, a treatment with methyl jasmonate, an elicitor hormone, increased scopolamine production 9.5-fold and decreased leaf growth 2.3-fold; a diet of artificially damaged leaves of B. suaveolens showed a negative effect on the growth of larvae of S. furgiperda compared to undamaged leaves, suggesting that damage by herbivores induces resistance. Our data are in line with the optimal-defense theory, but experiments in the field with herbivores that share an evolutionary history with B. suaveolens must be undertaken to understand the dynamics of TA allocation in response to herbivory.

Acetates↗
PubMed2001

How long should telomeres be?

What began as a study of the "end-replication problem" took on a new dimension as it became clear that telomeres are a "molecular clock" of replication in human somatic cells. Here we review the biology of telomeres in vitro and in vivo, in mice and humans. We suggest that, in humans, telomeres are involved in the biology of aging and pathobiology of disorders of aging, including cancer and cardiovascular disease. We also propose that the underlying dynamics of telomere biology is in line with broad principles of evolutionary theories.

Aging↗
PubMed2000

Are there pros as well as cons to being parasitized?

The diversity of ways in which parasites reduce the fitness of their hosts has been documented during the past decades, and clearly indicates that parasites can often be considered as direct agents of selection. In natural systems, however, the outcome of a host-parasite interaction might be strongly determined by other ecological factors. Parasites can be detrimental to host fitness in one environment, whereas they can be beneficial to it in another. From an evolutionary perspective, this phenomenon is of considerable importance for understanding the dynamics of coevolution among geographically structured populations evolving under different ecological pressures. Here, Frédéric Thomas and colleagues review several ecological situations in which parasitized individuals enjoy a selective advantage over unparasitized conspecifics.

Animals↗
PubMed2001

Evolution of 17beta-HSD type 4, a multifunctional protein of beta-oxidation.

17beta-Hydroxysteroid dehydrogenase type 4 (17beta-HSD4) is the most unusual among human 17beta-HSDs. It is characterized by a multidomain structure, in which the dehydrogenase domain is fused to a hydratase and a lipid transfer domain. 17beta-HSD4 not only inactivates estradiol by conversion to estrone but its three protein domains also participate in successive steps of peroxisomal beta-oxidation of long- and branched-chain fatty acids. We have compared the genomic structure of human 17beta-HSD4 and several homologous genes from lower animals and fungi. Our data suggest an evolutionary scenario for the three protein domains and indicate a highly dynamic history of the enzyme but also a very high conservation of multifunctionality. This suggests that the main function of human 17beta-HSD4 is still its involvement in fatty-acid metabolism, while steroid conversion is only a secondary and possibly minor activity in vivo.

17-Hydroxysteroid Dehydrogenases↗
PubMed2004

Appearing truthful generalizes across different deception situations.

The authors investigated whether the ability to appear truthful is specific to deception situations. Male participants were interrogated after they took part in 2 high-stake deception situations, one involving a mock crime and another involving a false opinion. The videotaped interrogations from each situation were shown to independent groups of undergraduate observers. The proportion of observers who judged each participant as truthful in one situation correlated highly with the proportion of observers who judged the same participant as truthful in the other situation. This was not correlated with physiognomy judgments. Follow-up studies revealed that although the participants showed consistency in their facial, body, and paralinguistic behaviors across situations, observers' judgments seemed to be driven only by the consistency of the dynamic facial behaviors. These results are discussed in terms of the evolutionary importance of the face in communication.

Adolescent↗
PubMed1983

Evolution of a finite population under gene conversion.

Evolution at a multiallelic locus under the joint action of gene conversion, mutation, selection, and random genetic drift is studied. Generations are discrete and nonoverlapping; the diploid, monoecious population mates at random. Under the assumption that all four evolutionary forces are weak, a diffusion approximation is established for the dynamics of the gene frequencies. For two alleles, the inclusion of gene conversion merely alters one of the two selection parameters of the thoroughly investigated diffusion process without conversion. Therefore, all results for this classical process, some of which are reviewed and extended here, are immediately applicable to the biologically more general problem. Small conversional disparities can dramatically affect the fixation probability (and hence the rate of gene substitution) and can greatly reduce the mean conditional fixation time of a new mutant. The mean absorption and fixation times are often sufficiently short to imply that biased gene conversion can be an important mechanism for the loss of genetic variability in and the genetic divergence of isolated populations.

Alleles↗
PubMed2004

Rapid sequence turnover at an intergenic locus in Drosophila.

Closely related species of Drosophila tend to have similar genome sizes. The strong imbalance in favor of small deletions relative to insertions implies that the unconstrained DNA in Drosophila is unlikely to be passively inherited from even closely related ancestors, and yet most DNA in Drosophila genomes is intergenic and potentially unconstrained. In an attempt to investigate the maintenance of this intergenic DNA, we studied the evolution of an intergenic locus on the fourth chromosome of the Drosophila melanogaster genome. This 1.2-kb locus is marked by two distinct, large insertion events: a nuclear transposition of a mitochondrial sequence and a transposition of a nonautonomous DNA transposon DNAREP1_DM. Because we could trace the evolutionary histories of these sequences, we were able to reconstruct the length evolution of this region in some detail. We sequenced this locus in all four species of the D. melanogaster species complex: D. melanogaster, D. simulans, D. sechellia, and D. mauritiana. Although this locus is similar in size in these four species, less than 10% of the sequence from the most recent common ancestor remains in D. melanogaster and all of its sister species. This region appears to have increased in size through several distinct insertions in the ancestor of the D. melanogaster species complex and has been shrinking since the split of these lineages. In addition, we found no evidence suggesting that the size of this locus has been maintained over evolutionary time; these results are consistent with the model of a dynamic equilibrium between persistent DNA loss through small deletions and more sporadic DNA gain through less frequent but longer insertions. The apparent stability of genome size in Drosophila may belie very rapid sequence turnover at intergenic loci.

Animals↗
PubMedDate not supplied

A design improvement strategy for axial blood pumps using computational fluid dynamics.

During the initial stages of concept development of non traditional axial flow pumps, numeric simulation offers an attractive advantage. Computational fluid dynamics (CFD) provides the rationale to evolve the design numerically such that undesirable flow features may be significantly mitigated before a physical prototype is fabricated. The initial design of a novel axial flow blood pump is shown through CFD analysis to exhibit large regions of reverse flow. Such fluid dynamic behavior not only decreases the pump's hydrodynamic efficiency, but, more significantly, increases its overall potential for blood trauma and thrombogenesis. The design improvement strategy consists of creating a geometric model of the blood wetted surfaces and changing the associated geometric parameters such that more desirable fluid dynamic behavior is systematically attained with each incremental modification. The fluid flow through each new pump design is analyzed by numerically solving the incompressible Navier-Stokes equations in rotating coordinates. Marked improvements in the major fluid dynamic aspects of the axial flow pump were observed over an evolutionary sequence of four generations of pump design.

Biomechanical Phenomena↗
PubMed1994

Recognition and polymorphism in host-parasite genetics.

Genetic specificity occurs in many host-parasite systems. Each host can recognize and resist only a subset of parasites; each parasite can grow only on particular hosts. Biochemical recognition systems determine which matching host and parasite genotypes result in resistance or disease. Recognition systems are often associated with widespread genetic polymorphism in the host and parasite populations. I describe four systems with matching host-parasite polymorphisms: plant-pathogen interactions, nuclear-cytoplasmic conflict in plants, restriction enzymes in bacterial defence against viruses, and bacterial plasmids that compete by toxin production and toxin immunity. These systems highlight several inductive problems. For example, the observed patterns of resistance and susceptibility between samples of hosts and parasites are often used to study polymorphism. The detectable polymorphism by this method may be a poor guide to the actual polymorphism and to the underlying biochemistry of host-parasite recognition. The problem of using detectable polymorphism to infer the true nature of recognition and polymorphism is exacerbated by non-equilibrium fluctuations in allele frequencies that commonly occur in host-parasite systems. Another problem is that different matching systems may lead either to low frequencies of host resistance and common parasites, or to common resistance and rare parasites. Thus low levels of host resistance or rare parasites do not imply that parasitism is an unimportant evolutionary force on host diversity. Knowledge of biochemical recognition systems and dynamical analysis of models provide a framework for analysing the widespread polymorphisms in host-parasite genetics.

Animals↗
PubMed2006

Allopatric origins of microbial species.

Although allopatric divergence is a well-accepted mechanism of speciation for eukaryotic macro-organisms, the importance of geographical barriers to divergence in microbial populations is a subject of great debate. Do geographically separated populations of micro-organisms diverge independently, or does their structure fit the often quoted Bass-Becking description 'everything is everywhere; the environment selects'? Aided by high-resolution genetic and genomic tools, the search for 'microbial marsupials' has revealed that in fact both are true; some species of micro-organisms demonstrate allopatric divergence, while others do not. This discovery opens the door for comparative analyses, where questions about the differences in evolutionary and ecological mechanisms that drive divergence and speciation in different microbial species can begin to be explored. Investigating these differences in evolutionary mechanisms will greatly enhance interest in, and understanding of, the dynamic processes that create and maintain the vast diversity of the microbial world.

Bacteria↗
PubMed2025

Transcriptome-wide analysis reveals sequence selection to avoid mRNA aggregation in E. coli.

The stability of RNA base pairing and its limited four-letter code create an intrinsic potential for promiscuous RNA-RNA interactions. In vitro, such interactions drive RNA to self-assemble into aggregates. This raises a fundamental unanswered question: within a confined cellular volume at physiological mRNA abundances, how much aggregation would arise from sequence-encoded chemistry alone? Here, we establish this baseline with large-scale kinetic simulations of the E. coli transcriptome. Our simulations reveal that sequence-encoded base-pairing energetics is sufficient to generate a dynamic network of large aggregates, organized by long, multivalent mRNA hubs. Strikingly, evolutionary analysis shows that native E. coli sequences exhibit clear signatures of selection to counteract this propensity: they fold more stably, minimize unstructured regions, and form weaker intermolecular contacts than dinucleotide-preserving controls. These findings demonstrate that maintaining transcriptome solubility has been a significant, previously unrecognized constraint shaping genome evolution, and provide a new lens to interpret cellular RNA management.

Biological Sciences (Biophysics and Computational ↗