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PubMed2000

Sequence conservation and variability of imprinting in the Beckwith-Wiedemann syndrome gene cluster in human and mouse.

In human and mouse most imprinted genes are arranged in chromosomal clusters. This linked organization suggests coordinated mechanisms controlling imprinted expression. We have sequenced 250 kb in the centre of the mouse imprinting cluster on distal chromosome 7 and compared it with the orthologous Beckwith-Wiedemann gene cluster on human chromosome 11p15.5. This first comparative imprinting cluster analysis revealed a high structural and functional conservation of the six orthologous genes identified. However, several striking differences were also discovered. First, compared with the mouse the human sequence is approximately 40% longer, mostly due to insertions of two large repetitive clusters. One of these clusters encompasses an additional gene coding for a homologue of the ribosomal protein L26. Second, pronounced blocks of unique direct repeats characteristic of imprinted genes were only found in the human sequence. Third, two of the orthologous gene pairs Tssc4/TSSC4 and Ltrpc5/LTRPC5 showed apparent differences in imprinting between human and mouse, whereas others like Tssc6/TSSC6 were not imprinted in either organism. Together these results suggest a significant functional and structural variability in the centre of the imprinting cluster. Some genes escape imprinting in both organisms whereas others exhibit tissue- and species-specific imprinting. Hence the control of imprinting in the cluster appears to be a highly dynamic process under fast evolutionary adaptation. Intriguingly, whereas imprinted genes within the cluster contain CpG islands the non-imprinted Ltrpc5 and Tssc6/TSSC6 do not. This and additional comparisons with other imprinted and non-imprinted regions suggest that CpG islands are key features of imprinted domains.

Amino Acid Sequence↗
PubMed2026

Computational mass spectrometry and genome mining guided discovery of metallophores produced by Microbulbifer.

Iron is an essential component of cellular biology. Thus, iron's low bioavailability is a key evolutionary pressure guiding microbial dynamics in the marine environment. Among marine bacteria, Microbulbifer is a chemically underexplored and functionally versatile bacterial genus, which is commonly associated with sponges, algae, corals, and sediments. Previously, genome analyses have revealed that Microbulbifer spp. can degrade polymers and synthesize natural products. Despite their recognized potential to produce secondary metabolites, siderophores are yet to be identified in Microbulbifer, and their iron acquisition strategies remain largely unknown. Here, we developed a comprehensive mass spectrometry-based query language code to determine siderophore production by Microbulbifer spp. in mono- and mixed cultures. Using this workflow, we discovered a new metallophore, which we named bulbichelin, as well as a suite of previously unreported petrobactins containing an unprecedented longer chain length acylation on the central spermidine moiety. We applied genome mining methods to describe the biosynthesis of these compounds. Using metal infusion mass spectrometry, we show that bulbichelins bind a variety of metals. Notably, neither of these compounds were produced in a co-culture of Microbulbifer with coral-derived pathogen Vibrio coralliilyticus Cn52-H1. Understanding how siderophores shape interspecies interactions between Microbulbifer spp. and other marine organisms will aid in unraveling the chemical and catalytic versatility of this genus and adaptation in nutrient deplete marine environment.

MassQL↗
PubMed1999

Different trajectories of parallel evolution during viral adaptation.

The molecular basis of adaptation is a major focus of evolutionary biology, yet the dynamic process of adaptation has been explored only piecemeal. Experimental evolution of two bacteriophage lines under strong selection led to over a dozen nucleotide changes genomewide in each replicate. At least 96 percent of the amino acid substitutions appeared to be adaptive, and half the changes in one line also occurred in the other. However, the order of these changes differed between replicates, and parallel substitutions did not reflect the changes with the largest beneficial effects or indicate a common trajectory of adaptation.

Adaptation, Physiological↗
PubMed2026

Landscape of retron diversity across the SPIRE microbial metagenome resource reveals candidate novel type XI-like lineages.

Retrons are bacterial genetic elements encoding a specialized reverse transcriptase (RT) that synthesizes multicopy single-stranded DNA and are increasingly recognized as components of bacterial anti-phage defense systems. However, their diversity and ecological distribution across large-scale genomic resources remain poorly characterized. Here, we surveyed retron RTs across the SPIRE representative metagenome collection, a non-redundant, species-level data set spanning diverse microbial habitats. Using a curated panel of type-specific hidden Markov models, we identified retrons representing all canonical types together with additional divergent lineages. Retron distribution showed strong taxonomic and ecological structuring, with some groups restricted to specific bacterial phyla, whereas others were broadly distributed across environmental categories. Systematic novelty assessment identified two candidate type XI-like lineages, TXI_C2like and TXI_noncan_h, characterized by protease-independent architectures and distinct accessory modules associated with WYL- and DnaB_C-containing proteins, respectively. De novo covariance-based analyses further identified candidate msr/msd-like non-coding RNA structures in both lineages, supporting conservation of the canonical RT-ncRNA organizational framework despite extensive sequence divergence. Together, these findings expand the known diversity of retron systems and identify type XI-like retrons as a dynamic and previously underexplored evolutionary group.IMPORTANCERetrons are bacterial genetic elements that are increasingly exploited as programmable tools for genome editing, molecular recording, and biosensing in addition to their natural role in anti-phage defense. Despite this growing biotechnological interest, the true diversity of retrons across the bacterial world has remained largely unmapped. By mining a resource of over 100,000 processed microbial metagenomes, we uncovered thousands of retron sequences spanning known types as well as previously unrecognized lineages and found that their distribution is strongly shaped by both bacterial taxonomy and ecological niche. Among these, we identified two candidate new lineages related to type XI retrons that lack the protease domain typical of this group but instead carry distinct accessory proteins, expanding the known architectural diversity of these systems. These findings broaden the catalog of retron diversity available for functional characterization and biotechnological engineering and provide a framework for prioritizing candidate lineages for future experimental validation.

effectors↗
PubMed2006

A CR1 element is embedded in a novel tandem repeat (HinfI repeat) within the chicken genome.

Highly repetitive DNA sequences constitute a significant portion of most eukaryotic genomes, raising questions about their evolutionary origins and amplification dynamics. In this study, a novel chicken repetitive DNA family, the HinfI repeat, was characterized. The basic repeating unit of this family displays a uniform length of 770 bp, which was defined by the recognition site of HinfI. The HinfI repeat was specifically localized in the pericentric region of chromosome 4 by fluorescence in situ hybridization and constitutes 0.51% of the chicken genome. Interestingly, a chicken repeat 1 (CR1) element has been identified within this basic repeating unit. Like other CR1 elements, this CR1 element also displays typical retrotransposition characteristics, including a highly conserved 3' region and a badly truncated 5' end. This direct evidence from sequence analysis, together with our Southern blot results, suggests that the HinfI repeat may originate from a unique region containing a retrotransposed CR1 element.

Animals↗
PubMed2001

Protein folding theory: from lattice to all-atom models.

This review focuses on recent advances in understanding protein folding kinetics in the context of nucleation theory. We present basic concepts such as nucleation, folding nucleus, and transition state ensemble and then discuss recent advances and challenges in theoretical understanding of several key aspects of protein folding kinetics. We cover recent topology-based approaches as well as evolutionary studies and molecular dynamics approaches to determine protein folding nucleus and analyze other aspects of folding kinetics. Finally, we briefly discuss successful all-atom Monte-Carlo simulations of protein folding and conclude with a brief outlook for the future.

Cell Nucleus↗
PubMed2006

Comparative analysis of the paired immunoglobulin-like receptor (PILR) locus in six mammalian genomes: duplication, conversion, and the birth of new genes.

Manyaspects of the immune system are controlled by homologous cell surface receptors that mediate inhibitory and activating pathways. The paired immunoglobulin-like receptor (PILR) locus at 7q22 encodes both PILRA, an inhibitory receptor, and PILRB, its activating counterpart. Mouse Pilrb1 is a novel immune system regulator, and its ligand Cd99 participates in the recruitment of T-cells to inflamed tissue. We characterized the PILR locus in six mammalian genomes and investigated the structure and mRNA expression of human PILRB. Synteny at the PILR locus is conserved in the human, chimpanzee, dog, mouse and rat genomes. The absence of the PILR locus in opossum and chicken genomes suggests it arose after the divergence of placental and nonplacental mammals. In humans, a Williams-Beuren syndrome-related segmental duplication has created a complex chimeric transcript representing the predominantly expressed form of PILRB. Unlike PILRA, PILRB transcripts were detected in a wide variety of tissues including cells of the lymphoid lineage. In the mouse genome, a second activating gene, Pilrb2, and six pseudogenes were found. Extensive gene duplications in the rat genome have resulted in at least 27 Pilrb genes and or pseudogenes. Abundant gene duplication events involving novel CD99-related genes were also detected in the rat genome. In addition to duplication, we show that gene conversion has played a persistent role in the evolution of the PILR genes. Overall, we demonstrate that the PILR locus is dynamically evolving via multiple evolutionary mechanisms in several mammalian genomes.

Animals↗
PubMed2005

Web-based resources for comparative genomics.

The available web-based genome data and related resources provide great opportunities for biomedical scientists to identify functional elements in a particular genome region or to explore the evolutionary pattern of genome dynamics. Comparative genomics is an indispensable tool for achieving these goals. Because of the broad scope of comparative genomics, it is difficult to address all of its aspects in this short survey. A few currently 'hot' topics have therefore been selected and a brief review of the availability of web-based databases and software is given.

Animals↗
PubMed2006

Age determination in individual wild-caught Drosophila serrata using pteridine concentration.

Fluorescence spectrophotometry can reliably detect levels of the pteridine 6-biopterin in the heads of individual Drosophila serrata Malloch 1927. Pteridine content in both laboratory and field captured flies is typically a level of magnitude higher than the minimally detectable level (mean(lab)=0.54 units, mean(field)=0.44 units, minimum detectable level=0.01 units) and can be used to predict individual age in laboratory populations with high certainty (r2=57%). Laboratory studies of individuals of known age (from 1 to 48 days old) indicate that while pteridine level increases linearly with age, they also increase in a linear manner with rearing temperature and ambient light levels, but are independent of sex. As expected, the longevity of laboratory-reared males (at least 48 days) is higher than the range of predicted ages of wild-caught males based on individual pteridine levels (40 days). However, the predictive equation based on pteridine level alone suggested that a number of wild-caught males were less than 0 days old, and the 95% confidence limits for these predictions based on the inverse regression are broad. The age of the oldest wild-caught male is predicted to fall within the range of 2 to 50 days. The significant effects of temperature and light intensity determined in the laboratory study (effect sizes omega2=14.3 and 20.4%, respectively) suggests that the calibration of the age prediction equation for field populations would be significantly improved when combined with fine-scaled studies of habitat temperature and light conditions. The ability to determine relative age in individual wild-caught D. serrata presents great opportunities for a variety of evolutionary studies on the dynamics of natural populations.

Aging↗
PubMed2006

An evolutionary strategy for all-atom folding of the 60-amino-acid bacterial ribosomal protein l20.

We have investigated an evolutionary algorithm for de novo all-atom folding of the bacterial ribosomal protein L20. We report results of two simulations that converge to near-native conformations of this 60-amino-acid, four-helix protein. We observe a steady increase of "native content" in both simulated ensembles and a large number of near-native conformations in their final populations. We argue that these structures represent a significant fraction of the low-energy metastable conformations, which characterize the folding funnel of this protein. These data validate our all-atom free-energy force field PFF01 for tertiary structure prediction of a previously inaccessible structural family of proteins. We also compare folding simulations of the evolutionary algorithm with the basin-hopping technique for the Trp-cage protein. We find that the evolutionary algorithm generates a dynamic memory in the simulated population, which leads to faster overall convergence.

Algorithms↗
PubMed2002

[MHC and its application in the population and conservation genetics].

The major histocompatibility complex (MHC),with the highest genetic polymorphism,is a cluster of genes involved in immune response regulation in the vertebrates.MHC can provide information such as population genetic diversity,evolutionary history and population dynamics,and population genetic structure etc. It can also be applied in the captive breeding programme for endangered vertebrate species.

English Abstract↗
PubMed2003

Using guide trees to construct multiple-sequence evolutionary HMMs.

MOTIVATION: Score-based progressive alignment algorithms do dynamic programming on successive branches of a guide tree. The analogous probabilistic construct is an Evolutionary HMM. This is a multiple-sequence hidden Markov model (HMM) made by combining transducers (conditionally normalised Pair HMMs) on the branches of a phylogenetic tree. METHODS: We present general algorithms for constructing an Evolutionary HMM from any Pair HMM and for doing dynamic programming to any Multiple-sequence HMM. RESULTS: Our prototype implementation, Handel, is based on the Thorne-Kishino-Felsenstein evolutionary model and is benchmarked using structural reference alignments.

Algorithms↗
PubMed2002

Sex differences in behavioral and hormonal response to social threat: commentary on Taylor et al. (2000).

Taylor and colleagues proposed that women uniquely respond to stressors by tending to children and befriending other women rather than by fighting or fleeing (S. E. Taylor et al., 2000). In this article, the authors expand Taylor et al.'s evolutionary frame and incorporate several unique aspects of human social dynamics. First, humans are characterized by extensive paternal investment, and thus men's tending is predicted and observed in some stressful contexts. Second, the dynamics of women's befriending suggest an evolutionary elaboration of the mechanisms that support reciprocal altruism. Third, coalitional male-male competition indicates that men's befriending is a predicted component of their fight-or-flight response. Finally, men's tending should result in the evolution of female-female competition over this form of parental investment.

Altruism↗
PubMed2005

20 questions on adaptive dynamics.

Adaptive Dynamics is an approach to studying evolutionary change when fitness is density or frequency dependent. Modern papers identifying themselves as using this approach first appeared in the 1990s, and have greatly increased up to the present. However, because of the rather technical nature of many of the papers, the approach is not widely known or understood by evolutionary biologists. In this review we aim to remedy this situation by outlining the methodology and then examining its strengths and weaknesses. We carry this out by posing and answering 20 key questions on Adaptive Dynamics. We conclude that Adaptive Dynamics provides a set of useful approximations for studying various evolutionary questions. However, as with any approximate method, conclusions based on Adaptive Dynamics are valid only under some restrictions that we discuss.

Adaptation, Biological↗
PubMed2000

Single column discrepancy and dynamic max-mini optimizations for quickly finding the most parsimonious evolutionary trees.

MOTIVATION: In the maximum parsimony (MP) method, the tree requiring the minimum number of changes (discrepancy) to explain the given set of DNA or amino acid sequences is chosen to represent their evolutionary relationships. To find the MP tree, the branch-and-bound algorithm is normally used. For a partial phylogenetic-tree (one that has a subset of the organisms) the traditional algorithm assigns a cost equal to the discrepancy of the partial phylogenetic-tree. We propose a single column discrepancy heuristic which increases this cost by predicting a minimum additional discrepancy needed to attach the sequences yet to be added to the partial phylogenetic-tree. A dynamic Max-mini order of sequence addition is also proposed to quickly terminate branch-and-bound search paths that are guaranteed to lead to suboptimal solutions. RESULTS: We studied the running time of 47 problems generated from 17 data sets. The use of single column discrepancy heuristic speeded up the computation to 2.4-fold for static and 18.2-fold for dynamic search order. The improvement appeared to increase exponentially with the number of sequences. The proposed strategies are also likely to be useful in speeding up the MP tree search using heuristic searches that are based on branch-and-bound-like algorithms. CONTACT: s.kumar@asu.edu

Amino Acids↗
PubMed2003

Enhancing evolvability with mutation buffering mediated through multiple weak interactions.

The evolutionary adaptability of a system is dependent on three organizational properties, self-organizing dynamics that are hierarchically organized, component redundancy, and multiple weak interactions [Towards high evolvability dynamics, in: G. van de Vijver, S. Salthe, M. Delpos (Eds.), Evolutionary Systems, Kluwer Academic Publishers, Dordrecht, 1998, pp. 147-169]. This study reports on the use of the dual dynamics network model as an aid in understanding the role multiple weak interactions play in enhancing evolutionary adaptability. Dual dynamics networks are self-organizing systems that consist of simple components that change local state due to the coupled influences from connected components exerting strong discrete decision-making influences and from groups of components exerting multiple weak influences [J. Theor. Biol. 193 (1998) 287]. The dual dynamics model has been enhanced to support investigations of properties relevant to a system's capacity for evolvability, such as structure-function relationships, neutrality, adaptive tolerance, and evolutionary search performance. Three network types are investigated, each utilizing a different method of coupling strong and weak influences. The results demonstrate that the manner of coupling multiple weak interactions into the systems dynamics significantly affects the structure-function maps and the consequent evolvability characteristics. Specifically it is found that a form of coupling, denoted as linear modulation, enhances evolutionary adaptability. Linear modulation coupling requires that the weak interactions be integrated with strong interactions in a manner that implies a linear ordered relation between the possible state values of the components of the systems. When coupling functions that do not imply such an ordering of local state values are used, evolutionary adaptability is decreased.

Adaptation, Physiological↗
PubMed2006

Phylogeography of Ustilago maydis virus H1 in the USA and Mexico.

Ustilago maydis virus H1 (Umv-H1) is a mycovirus that infects Ustilago maydis, a fungal pathogen of maize. As Zea mays was domesticated, it carried with it many associated symbionts, such that the subsequent range expansion and cultivation of maize should have affected maize symbionts' evolutionary history dramatically. Because transmission of Umv-H1 takes place only through cytoplasmic fusion during mating of U. maydis individuals, the population dynamics of U. maydis and maize are expected to affect the population structure of the viral symbiont strongly. Here, the impact of changes in the evolutionary history of U. maydis on that of Umv-H1 was investigated. The high mutation rate of this virus allows inferences to be made about the evolution and divergence of Umv-H1 lineages as a result of the recent changes in U. maydis geographical and genetic structure. The phylogeographical history and genetic structure of Umv-H1 populations in the USA and Mexico were determined by using analyses of viral nucleotide sequence variation. Infection and recombination frequencies, genetic diversity and rates of neutral evolution were also assessed, to make inferences regarding evolutionary processes underlying the population genetic structure of ancestral and descendent populations. The results suggest that Mexico represents the ancestral population of Umv-H1, from which the virus has been carried with U. maydis populations into the USA. Thus, the population dynamics of one symbiont represent a major evolutionary force on the co-evolutionary dynamics of symbiotic partners.

Capsid↗
PubMed2006

Emergent criticality from coevolution in random Boolean networks.

The coevolution of network topology and dynamics is studied in an evolutionary Boolean network model that is a simple model of a gene regulatory network. We find that a critical state emerges spontaneously resulting from the interplay between topology and dynamics during the evolution. The final evolved state is shown to be independent of initial conditions. The network appears to be driven to a random Boolean network with uniform in-degree of 2 in the large-network limit. However, for biologically realized network sizes, significant finite-size effects are observed including a broad in-degree distribution and an average in-degree connections between 2 and 3. These results may be important for explaining the properties of gene regulatory networks.

Cell Physiological Phenomena↗