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Results for “regulatory evolution”

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At least 811 records · Page 45Linked to original sources

PubMed2005

Plant metabolic diversity: a regulatory perspective.

Plants accumulate an amazing diversity of phytochemicals that play important roles in the interaction of plants with the environment. Mechanisms have been proposed to describe the evolution of phytochemicals from the perspective of the biosynthetic enzymes. However, it is not known how the transcription factors that regulate these pathways have evolved to ensure the coordinate expression of all the genes in a pathway. A model is provided here to explain how duplication and divergence of regulatory genes result in the control of new pathways. In this model, the purported ability of recently duplicated regulatory genes to activate new metabolic pathways is a consequence of mutations that partially impair function, resulting in the loss of activation of one or several steps in a metabolic pathway. Consequently, pathway intermediates accumulate and are then converted into new compounds by broad-specificity enzymes. In contrast to the resilience of developmental regulatory circuits, this model provides an explanation for the rapid evolution of new metabolic pathways from existing ones.

Enzymes↗

PubMed2005

An analytical study of the number of steady states in gene regulatory networks.

Herein, I proposed a model for gene networks and studied the steady states in the dynamics both by numerical and analytical methods. In this model, mRNA and protein levels change continuously with time; each gene alters transcriptional regulation depending on the concentration of transcription factors. The dynamical behavior of continuous model is quite complex and different from that of the discrete model, the Boolean network. Large portion of steady states of this model can be classified into three types. The rough structure of gene interactions, which corresponds to Boolean function, is sufficient to predict the expression level of each gene in these types of steady states. I also determined the expected numbers of two major types of steady states observed in a randomly generated gene network. The results obtained from these formulae contradict previously accepted belief. The results are that neither gene number nor connectivity between genes increases the expected number of steady states in a random gene network. The number of steady states is very small. The number of self-regulatory genes, however, effectively increases the number of steady states in a network. These results imply that increases in gene number may not be the direct driving force for the evolution of a variety of different cell types within organisms. Instead, the number of self-regulatory genes may significantly increase cellular diversity.

Animals↗

PubMed2004

Upstream plasticity and downstream robustness in evolution of molecular networks.

BACKGROUND: Gene duplication followed by the functional divergence of the resulting pair of paralogous proteins is a major force shaping molecular networks in living organisms. Recent species-wide data for protein-protein interactions and transcriptional regulations allow us to assess the effect of gene duplication on robustness and plasticity of these molecular networks. RESULTS: We demonstrate that the transcriptional regulation of duplicated genes in baker's yeast Saccharomyces cerevisiae diverges fast so that on average they lose 3% of common transcription factors for every 1% divergence of their amino acid sequences. The set of protein-protein interaction partners of their protein products changes at a slower rate exhibiting a broad plateau for amino acid sequence similarity above 70%. The stability of functional roles of duplicated genes at such relatively low sequence similarity is further corroborated by their ability to substitute for each other in single gene knockout experiments in yeast and RNAi experiments in a nematode worm Caenorhabditis elegans. We also quantified the divergence rate of physical interaction neighborhoods of paralogous proteins in a bacterium Helicobacter pylori and a fly Drosophila melanogaster. However, in the absence of system-wide data on transcription factors' binding in these organisms we could not compare this rate to that of transcriptional regulation of duplicated genes. CONCLUSIONS: For all molecular networks studied in this work we found that even the most distantly related paralogous proteins with amino acid sequence identities around 20% on average have more similar positions within a network than a randomly selected pair of proteins. For yeast we also found that the upstream regulation of genes evolves more rapidly than downstream functions of their protein products. This is in accordance with a view which puts regulatory changes as one of the main driving forces of the evolution. In this context a very important open question is to what extent our results obtained for homologous genes within a single species (paralogs) carries over to homologous proteins in different species (orthologs).

Animals↗

PubMed2000

Evolution of cis-acting elements in 5' flanking regions of vertebrate actin genes.

Regulation of the vertebrate actin multigene family involves the recognition of various regulatory sequences (cis-acting elements) that specify the distinct tissue type and developmental program of expression for each actin paralogue, which implies that the distribution of cis-acting elements may be unique for each paralogue gene. To elucidate the evolution of these unique distribution patterns, we improved a method to scan for cis-acting elements in the 5' flanking regulatory region of genes and used it to analyze five cis-acting elements (SRE, MyoD binding site, Elk-1 binding site, positive and negative YY1 binding sites) of six actin paralogue genes (beta and gamma cytoplasmic actins, alpha and gamma smooth muscle actins, and alpha skeletal and alpha cardiac actins) among various vertebrates. It was shown that although an element(s) may exist in all paralogue genes of the same species, its numbers, compositions, and distribution patterns or even sequences vary remarkably among paralogues, which contributes to their different tissue- and developmental-specific expression. However, each pair of coexpressed paralogues has some certain similarity in distribution patterns. Furthermore, among various orthologues of actin genes derived from diverse vertebrates, the sequences, numbers, and distribution patterns of these cis-acting elements are highly conserved or even identical in the long run of phylogeny of vertebrates. Taken together, the results described above strongly indicate that not only the structures of actins but also their expression patterns are essential in both the phylogeny and the physiology of vertebrates. The distribution patterns of cis-acting elements of various actin genes can be regarded as indicators of both horizontal (paralogues) and vertical (orthologous) evolution of actins.

Actins↗

PubMed1997

The complete genome sequence of the gastric pathogen Helicobacter pylori.

Helicobacter pylori, strain 26695, has a circular genome of 1,667,867 base pairs and 1,590 predicted coding sequences. Sequence analysis indicates that H. pylori has well-developed systems for motility, for scavenging iron, and for DNA restriction and modification. Many putative adhesins, lipoproteins and other outer membrane proteins were identified, underscoring the potential complexity of host-pathogen interaction. Based on the large number of sequence-related genes encoding outer membrane proteins and the presence of homopolymeric tracts and dinucleotide repeats in coding sequences, H. pylori, like several other mucosal pathogens, probably uses recombination and slipped-strand mispairing within repeats as mechanisms for antigenic variation and adaptive evolution. Consistent with its restricted niche, H. pylori has a few regulatory networks, and a limited metabolic repertoire and biosynthetic capacity. Its survival in acid conditions depends, in part, on its ability to establish a positive inside-membrane potential in low pH.

Antigenic Variation↗

PubMed2000

Combinatorial protein reagents to manipulate protein function.

The design and use of combinatorial protein libraries has become a fast moving field in molecular biology. Different experimental systems supporting various selection schemes are now available. The latest breakthroughs include evolutionary experiments to improve existing binding surfaces, selections of homodimerizing peptides, the use of peptide aptamers to disrupt protein interactions inside living cells, and functional selections of aptamers to probe regulatory networks.

Combinatorial Chemistry Techniques↗

PubMed2003

Identification and functional validation of a 5' upstream regulatory sequence in the human tyrosinase gene homologous to the locus control region of the mouse tyrosinase gene.

Comparison analysis of the sequences of the mouse and human genomes has proven a powerful approach in identifying functional regulatory elements within the non-coding regions that are conserved through evolution between homologous mammalian loci. Here, we applied computational analysis to identify regions of homology in the 5' upstream sequences of the human tyrosinase gene, similar to the locus control region (LCR) of the mouse tyrosinase gene, located at -15 kb. We detected several stretches of homology within the first 30 kb 5' tyrosinase gene upstream sequences of both species that include the proximal promoter sequences, the genomic region surrounding the mouse LCR, and further upstream segments. We cloned and sequenced a 5' upstream regulatory sequence found between -8 and -10 kb of the human tyrosinase locus (termed h5'URS) homologous to the mouse LCR sequences, and confirmed the presence of putative binding sites at -9 kb, homologous to those described in the mouse tyrosinase LCR core. Finally, we functionally validated the presence of a tissue-specific enhancer in the h5'URS by transient transfection analysis in human and mouse cells, as compared with homologous DNA sequences from the mouse tyrosinase locus. Future experiments in cells and transgenic animals will help us to understand the in vivo relevance of this newly described h5'URS sequence as a potentially important regulatory element for the correct expression of the human tyrosinase gene.

Albinism, Oculocutaneous↗

PubMed1998

Multilocus phylogeny of cichlid fishes (Pisces: Perciformes): evolutionary comparison of microsatellite and single-copy nuclear loci.

Among vertebrates, cichlid fishes are the paradigmatic example of adaptive radiation and ecological specialization. In turn, molecular genetic studies of cichlids have focused primarily on more recently diverged groups. Here, we present an evolutionary hypothesis of the major lineages of cichlid fishes based on DNA sequence data from two nuclear loci. One marker, Tmo-4C4, is a single-copy locus containing a region of amino acid similarity to the muscle protein TITIN. Flanking sequence from a second, microsatellite, locus Tmo-M27, shows similarity to mammalian RAS guanine nucleotide-releasing factor. We compare and combine data from these loci to evaluate phylogenetic performance. In separate and combined analyses, the sequence data support and clarify previous morphological hypotheses of cichlid major-group relationships. Indian and Malagasy cichlids form a basal, paraphyletic group. Neotropical cichlids are the sister clade to an African assemblage composed of the paraphyletic west and Pan-African lineages and a group of east African rift lake taxa. We use a consensus phylogeny of the Cichlidae to trace evolutionary changes in the microsatellite repeat motif at Tmo-M27. Analysis reveals that the repeat region was nearly lost in the ancestor to cichlids and then amplified extensively in African taxa. Results demonstrate that the two new DNA markers could be widely applied in perciform systematics. Furthermore, the comparative approach can unveil mutational dynamics of simple-sequence repeat loci over long periods of fish evolution. Simple-sequence repeat regions are increasingly being found in introns of important regulatory genes. We address issues involving their function and suggest caution in making assumptions of strict neutrality.

Animals↗

PubMed2006

BLISS: binding site level identification of shared signal-modules in DNA regulatory sequences.

BACKGROUND: Regulatory modules are segments of the DNA that control particular aspects of gene expression. Their identification is therefore of great importance to the field of molecular genetics. Each module is composed of a distinct set of binding sites for specific transcription factors. Since experimental identification of regulatory modules is an arduous process, accurate computational techniques that supplement this process can be very beneficial. Functional modules are under selective pressure to be evolutionarily conserved. Most current approaches therefore attempt to detect conserved regulatory modules through similarity comparisons at the DNA sequence level. However, some regulatory modules, despite the conservation of their responsible binding sites, are embedded in sequences that have little overall similarity. RESULTS: In this study, we present a novel approach that detects conserved regulatory modules via comparisons at the binding site level. The technique compares the binding site profiles of orthologs and identifies those segments that have similar (not necessarily identical) profiles. The similarity measure is based on the inner product of transformed profiles, which takes into consideration the p values of binding sites as well as the potential shift of binding site positions. We tested this approach on simulated sequence pairs as well as real world examples. In both cases our technique was able to identify regulatory modules which could not to be identified using sequence-similarity based approaches such as rVista 2.0 and Blast. CONCLUSION: The results of our experiments demonstrate that, for sequences with little overall similarity at the DNA sequence level, it is still possible to identify conserved regulatory modules based solely on binding site profiles.

Animals↗

PubMed2005

Regulation of phyllotaxis.

Plant architecture is characterized by a high degree of regularity. Leaves, flowers and floral organs are arranged in regular patterns, a phenomenon referred to as phyllotaxis. Regular phyllotaxis is found in virtually all higher plants, from mosses, over ferns, to gymnosperms and angiosperms. Due to its remarkable precision, its beauty and its accessibility, phyllotaxis has for centuries been the object of admiration and scientific examination. There have been numerous hypotheses to explain the nature of the mechanistic principle behind phyllotaxis, however, not all of them have been amenable to experimental examination. This is due mainly to the delicacy and small size of the shoot apical meristem, where plant organs are formed and the phyllotactic patterns are laid down. Recently, the combination of genetics, molecular tools and micromanipulation has resulted in the identification of auxin as a central player in organ formation and positioning. This paper discusses some aspects of phyllotactic patterns found in nature and summarizes our current understanding of the regulatory mechanism behind phyllotaxis.

Biological Evolution↗

PubMed2005

Contribution of transcriptional regulation to natural variations in Arabidopsis.

BACKGROUND: Genetic control of gene transcription is a key component in genome evolution. To understand the transcriptional basis of natural variation, we have studied genome-wide variations in transcription and characterized the genetic variations in regulatory elements among Arabidopsis accessions. RESULTS: Among five accessions (Col-0, C24, Ler, WS-2, and NO-0) 7,508 probe sets with no detectable genomic sequence variations were identified on the basis of the comparative genomic hybridization to the Arabidopsis GeneChip microarray, and used for accession-specific transcriptome analysis. Two-way ANOVA analysis has identified 60 genes whose mRNA levels differed in different accession backgrounds in an organ-dependent manner. Most of these genes were involved in stress responses and late stages of plant development, such as seed development. Correlation analysis of expression patterns of these 7,508 genes between pairs of accessions identified a group of 65 highly plastic genes with distinct expression patterns in each accession. CONCLUSION: Genes that show substantial genetic variation in mRNA level are those with functions in signal transduction, transcription and stress response, suggesting the existence of variations in the regulatory mechanisms for these genes among different accessions. This is in contrast to those genes with significant polymorphisms in the coding regions identified by genomic hybridization, which include genes encoding transposon-related proteins, kinases and disease-resistance proteins. While relatively fewer sequence variations were detected on average in the coding regions of these genes, a number of differences were identified from the upstream regions, several of which alter potential cis-regulatory elements. Our results suggest that nucleotide polymorphisms in regulatory elements of genes encoding controlling factors could be primary targets of natural selection and a driving force behind the evolution of Arabidopsis accessions.

Arabidopsis↗

PubMed1987

Evolution of the enterobacterial sulA gene: a component of the SOS system encoding an inhibitor of cell division.

The LexA-regulated sulA (sfiA) gene of Escherichia coli encodes an unstable protein which inhibits cell division. By determining the nucleotide sequences of the corresponding genes from the related bacteria Salmonella typhimurium, Enterobacter aerogenes and Serratia marcescens it was found that the regulatory region and the LexA binding site (SOS box) have been better conserved during evolution than the coding sequence. The N terminus of the SulA protein [amino acid (aa) residues 1-30] has diverged extensively during the evolution of Enterobacteriaceae, whereas the central region (aa residues 31-149) has been well conserved. At the C terminus a sequence showing some homology to the N protein of phage lambda was detected that may represent a recognition site for the Lon protease, which is known to degrade both polypeptides. When expressed in E. coli, the foreign sulA genes did not block cell division suggesting that their products are inactive. This may indicate that the N terminus of the SulA protein is involved in recognizing the cell division apparatus.

Amino Acid Sequence↗

PubMed2004

New regulatory regions of Drosophila 412 retrotransposable element generated by recombination.

There are no doubts that transposable elements (TEs) have greatly influenced genomes evolution. They have, however, evolved in different ways throughout mammals, plants, and invertebrates. In mammals they have been shown to be widely present but with low transposition activity; in plants they are responsible for large increases in genome size. In Drosophila, despite their low amount, transposition seems to be higher. Therefore, to understand how these elements have evolved in different genomes and how host genomes have proposed to go around them, are major questions on genome evolution. We analyzed sequences of the retrotransposable elements 412 in natural populations of the Drosophila simulans and D. melanogaster species that greatly differ in their amount of TEs. We identified new subfamilies of this element that were the result of mutation or insertion-deletion process, but also of interfamily recombinations. These new elements were well conserved in the D. simulans natural populations. The new regulatory regions produced by recombination could give rise to new elements able to overcome host control of transposition and, thus, become potential genome invaders.

Animals↗

PubMed2004

A probabilistic model for the evolution of RNA structure.

BACKGROUND: For the purposes of finding and aligning noncoding RNA gene- and cis-regulatory elements in multiple-genome datasets, it is useful to be able to derive multi-sequence stochastic grammars (and hence multiple alignment algorithms) systematically, starting from hypotheses about the various kinds of random mutation event and their rates. RESULTS: Here, we consider a highly simplified evolutionary model for RNA, called "The TKF91 Structure Tree" (following Thorne, Kishino and Felsenstein's 1991 model of sequence evolution with indels), which we have implemented for pairwise alignment as proof of principle for such an approach. The model, its strengths and its weaknesses are discussed with reference to four examples of functional ncRNA sequences: a riboswitch (guanine), a zipcode (nanos), a splicing factor (U4) and a ribozyme (RNase P). As shown by our visualisations of posterior probability matrices, the selected examples illustrate three different signatures of natural selection that are highly characteristic of ncRNA: (i) co-ordinated basepair substitutions, (ii) co-ordinated basepair indels and (iii) whole-stem indels. CONCLUSIONS: Although all three types of mutation "event" are built into our model, events of type (i) and (ii) are found to be better modeled than events of type (iii). Nevertheless, we hypothesise from the model's performance on pairwise alignments that it would form an adequate basis for a prototype multiple alignment and genefinding tool.

Evolution, Molecular↗

PubMed1999

Conserved and distinct roles of kreisler in regulation of the paralogous Hoxa3 and Hoxb3 genes.

During anteroposterior patterning of the developing hindbrain, the anterior expression of 3' Hox genes maps to distinct rhombomeric boundaries and, in many cases, is upregulated in specific segments. Paralogous genes frequently have similar anterior boundaries of expression but it is not known if these are controlled by common mechanisms. The expression of the paralogous Hoxa3 and Hoxb3 genes extends from the posterior spinal cord up to the rhombomere (r) 4/5 boundary and both genes are upregulated specifically in r5. However, in this study, we have found that Hoxa3 expression is also upregulated in r6, showing that there are differences in segmental expression between paralogues. We have used transgenic analysis to investigate the mechanisms underlying the pattern of segmental expression of Hoxa3. We found that the intergenic region between Hoxa3 and Hoxa4 contains several enhancers, which summed together mediate a pattern of expression closely resembling that of the endogenous Hoxa3 gene. One enhancer specifically directs expression in r5 and r6, in a manner that reflects the upregulation of the endogenous gene in these segments. Deletion analysis localized this activity to a 600 bp fragment that was found to contain a single high-affinity binding site for the Maf bZIP protein Krml1, encoded by the kreisler gene. This site is necessary for enhancer activity and when multimerized it is sufficient to direct a kreisler-like pattern in transgenic embryos. Furthermore the r5/r6 enhancer activity is dependent upon endogenous kreisler and is activated by ectopic kreisler expression. This demonstrates that Hoxa3, along with its paralog Hoxb3, is a direct target of kreisler in the mouse hindbrain. Comparisons between the Krml1-binding sites in the Hoxa3 and Hoxb3 enhancers reveal that there are differences in both the number of binding sites and way that kreisler activity is integrated and restricted by these two control regions. Analysis of the individual sites revealed that they have different requirements for mediating r5/r6 and dorsal roof plate expression. Therefore, the restriction of Hoxb3 to r5 and Hoxa3 to r5 and r6, together with expression patterns of Hoxb3 in other vertebrate species suggests that these regulatory elements have a common origin but have later diverged during vertebrate evolution.

Amino Acid Sequence↗

PubMed2026

Experimental evolution reveals genetic routes for adaptive loss of the antibacterial type VI secretion system.

The type VI secretion system (T6SS) is a contractile nanomachine used by Gram-negative bacteria to deliver effector proteins into target cells, contributing to both interbacterial competition and pathogenesis. Although T6SS gene clusters are present in recently isolated commensal and pathogenic Escherichia coli strains, they are absent from classical laboratory strains that have been propagated for decades in pure cultures, suggesting that T6SS can be lost in the absence of competition. Here, we combined experimental evolution with whole-genome sequencing to track the fate of the enteroaggregative Escherichia coli (EAEC) Sci1 T6SS during competition with either T6SS-susceptible or T6SS-immune bacteria. After ∼640 generations, T6SS activity was largely maintained during competition with T6SS-susceptible bacteria, whereas ∼90% of clones evolved with T6SS-immune bacteria lost or attenuated T6SS activity through diverse mutations within the sci1 promoter, essential T6SS structural genes, or the rfaH transcriptional antiterminator. We identified two RfaH-binding ops elements within the sci1 cluster, revealing antitermination as a regulatory element of EAEC T6SS transcription, which is conserved among Enterobacteriaceae. Our findings highlight how experimental evolution can reveal the selective forces shaping T6SS maintenance and identify new regulatory components controlling its activity.

Journal Article↗

PubMed2026

Plant cis-regulatory grammar: Decoding the multidimensional code of transcriptional regulation for programmable crop engineering.

Cis-regulatory elements (CREs) orchestrate the spatiotemporal precision of gene expression that underlies plant development, adaptation, and domestication. Decoding the cis-regulatory grammar of plant genomes remains a central challenge in modern biology, with profound implications for programmable crop engineering. Here, recent conceptual and technological advances are synthesized to reshape our understanding of plant CREs. This review first argues that CRE function is not only an intrinsic property of DNA sequence alone but also emerges from a multidimensional context, including chromatin accessibility, histone modifications, three-dimensional genome topology, and cell type-specific regulatory landscapes. Furthermore, the convergence of single-cell epigenomics, high-throughput functional assays, and CRISPR-based dissection has begun to unravel this contextual grammar, revealing the computational principles governing transcriptional regulation. Critically, we propose that artificial intelligence (AI) platforms are catalyzing an ongoing transition from descriptive discovery to predictive engineering, wherein these platforms outperform natural evolution in designing synthetic CREs. Finally, a roadmap is outlined toward a plant regulatory grammar foundation model, which will enable truly predictive engineering of gene expression when fine-tuned for specific tasks. Collectively, the integration of single-cell resolution maps, precise genome editing, AI-driven design, and regulatory-compliant delivery systems promises to transform our ability to reprogram plant gene regulation for next-generation agriculture, bridging the gap between foundational regulatory biology and tangible crop improvement.

artificial intelligence↗

PubMed1996

Development, plasticity and evolution of butterfly eyespot patterns.

The developmental and genetic bases for the formation, plasticity and diversity of eyespot patterns in butterflies are examined. Eyespot pattern mutants, regulatory gene expression, and transplants of the eyespot developmental organizer demonstrate that eyespot position, number, size and colour are determined progressively in a developmental pathway largely uncoupled from those regulating other wing-pattern elements and body structures. Species comparisons and selection experiments suggest that the evolution of eyespot patterns can occur rapidly through modulation of different stages of this pathway, and requires only single, or very few, changes in regulatory genes.

Adaptation, Biological↗