SEARCH · PubMed Health

Results for “regulatory evolution”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources

PubMed2006

The evolution of retrotransposon regulatory regions and its consequences on the Drosophila melanogaster and Homo sapiens host genomes.

It has now been established that transposable elements (TEs) make up a variable, but significant proportion of the genomes of all organisms, from Bacteria to Vertebrates. However, in addition to their quantitative importance, there is increasing evidence that TEs also play a functional role within the genome. In particular, TE regulatory regions can be viewed as a large pool of potential promoter sequences for host genes. Studying the evolution of regulatory region of TEs in different genomic contexts is therefore a fundamental aspect of understanding how a genome works. In this paper, we first briefly describe what is currently known about the regulation of TE copy number and activity in genomes, and then focus on TE regulatory regions and their evolution. We restrict ourselves to retrotransposons, which are the most abundant class of eukaryotic TEs, and analyze their evolution and the subsequent consequences for host genomes. Particular attention is paid to much-studied representatives of the Vertebrates and Invertebrates, Homo sapiens and Drosophila melanogaster, respectively, for which high quality sequenced genomes are available.

Animals↗

PubMed1995

[Regulatory selection as an alternative to the neutrality theory].

Regulatory selection is the most typical mode of natural selection responsible for the optimization of the regulatory systems of an organism. In addition to regulatory selection, stringent selection of pleiotropic mutants or recombinant forms with altered ecological potential operates in successful species during vertical evolution. Regulatory selection stabilizes alterations in the ecological potential, acting at intervals between larger regulatory genome alterations occurring at the boundaries between evolutionary phases. Fisher's adaptive model can be applied to regulatory selection. At each separate evolutionary phase, the selection coefficients in selected mutants decline gradually. At the final stage of the evolutionary phase, mutations with a minor selective advantage are selected. Hence, regulatory selection may be regarded as an alternative to the neutral evolution theory.

Animals↗

PubMed2000

Developmental regulatory genes and echinoderm evolution.

Modified interactions among developmental regulatory genes and changes in their expression domains are likely to be an important part of the developmental basis for evolutionary changes in morphology. Although developmental regulatory genes are now being studied in an increasing number of taxa, there has been little attempt to analyze the resulting data within an explicit phylogenetic context. Here we present comparative analyses of expression data from regulatory genes in the phylum Echinodermata, considering the implications for understanding both echinoderm evolution as well as the evolution of regulatory genes in general. Reconstructing the independent evolutionary histories of regulatory genes, their expression domains, their developmental roles, and the structures in which they are expressed reveals a number of distinct evolutionary patterns. A few of these patterns correspond to interpretations common in the literature, whereas others have received little prior mention. Together, the analyses indicate that the evolution of echinoderms involved: (1) the appearance of many apomorphic developmental roles and expression domains, some of which have plesiomorphic bilateral symmetry and others of which have apomorphic radial symmetry or left-right asymmetry; (2) the loss of some developmental roles and expression domains thought to be plesiomorphic for Bilateria; and (3) the retention of some developmental roles thought to be plesiomorphic for Bilateria, although with modification in expression domains. Some of the modifications within the Echinodermata concern adult structures; others, transient larval structures. Some changes apparently appeared early in echinoderm evolution (> 450 Ma), whereas others probably happened more recently (< 50 Ma). Cases of likely convergence in expression domains suggest caution when using developmental regulatory genes to make inferences about homology among morphological structures of distantly related taxa.

Animals↗

PubMed1998

A role of Ultrabithorax in morphological differences between Drosophila species.

The mechanisms underlying the evolution of morphology are poorly understood. Distantly related taxa sometimes exhibit correlations between morphological differences and patterns of gene expression, but such comparisons cannot establish how mechanisms evolve to generate diverse morphologies. Answers to these questions require resolution of the nature of developmental evolution within and between closely related species. Here I show how the detailed regulation of the Hox gene Ultrabithorax patterns trichomes on the posterior femur of the second leg in Drosophila melanogaster, and that evolution of Ultrabithorax has contributed to divergence of this feature among closely related species. The cis-regulatory regions of Ultrabithorax, and not the protein itself, appear to have evolved. This study provides experimental evidence that cis-regulatory evolution is one way in which conserved proteins have promoted morphological diversity.

Alleles↗

PubMed2000

Evolution of transcriptional regulation.

Major advances have been made in understanding the evolution of transcriptional regulation using microevolutionary and macroevolutionary experimental approaches. The roles of stabilising selection and compensatory changes in an enhancer region have been elucidated in Drosophila. The molecular dynamics of regulatory alleles have been studied in plants. Evidence is accumulating for the involvement of regulatory evolution in morphological changes between closely related species, as well as in major changes of body plans.

Animals↗

PubMed2006

Combinatorial epigenetics, "junk DNA", and the evolution of complex organisms.

At certain evolutionary junctures, two or more mutations participating in the build-up of a new complex function may be required to become available simultaneously in the same individuals. How could this happen in higher organisms whose populations are small compared to those of microbes, and in which chances of combined nearly simultaneous highly specific favorable mutations are correspondingly low? The question can in principle be answered for regulatory evolution, one of the basic processes of evolutionary change. A combined resetting of transcription rates in several genes could occur in the same individual. It is proposed that, in eukaryotes, changes in epigenetic trends and epigenetically transforming encounters between alternative chromatin structures could arise frequently enough so as to render probable particular conjunctions of changed transcription rates. Such conjunctions could involve mutational changes with low specificity requirements in gene-associated regions of non-protein-coding sequences. The effects of such mutations, notably when they determine the use of histone variants and covalent modifications of histones, can be among those that migrate along chromatin. Changes in chromatin structure are often cellularly inheritable over at least a limited number of generations of cells, and of individuals when the germ line is involved. SINEs and LINEs, which have been considered "junk DNA", are among the repeat sequences that would appear liable to have teleregulatory effects on the function of a nearby promoter, through changes in their numbers and distribution. There may also be present preexisting unstably inheritable epigenetic trends leading to cellular variegation, trends endemic in a cell population based on DNA sequences previously established in the neighborhood. Either way, epigenetically conditioned teleregulatory trends may display only limited penetrance. The imposition at a distance of new chromatin structures with regulatory impact can occur in cis as well as in trans, and is examined as intrachromosomally spreading teleregulation and interchromosomal "gene kissing". The chances for two or more particular epigenetically determined regulatory trends to occur together in a cell are increased thanks to the proposed low specificity requirements for most of the pertinent sequence changes in intergenic and intronic DNA or in the distribution of middle repetitive sequences that have teleregulatory impact. Inheritable epigenetic changes ("epimutations") with effects at a distance would then perdure over the number of generations required for "assimilation" of the several regulatory novelties through the occurrence and selection, gene by gene, of specific classical mutations. These mutations would have effects similar to the epigenetic effects, yet would provide stability and penetrance. The described epigenetic/genetic partnership may well at times have opened the way toward certain complex new functions. Thus, the presence of "junk DNA", through co-determining the (higher or lower) order and the variants of chromatin structure with regulatory effects at a distance, might make an important contribution to the evolution of complex organisms.

Animals↗

PubMed1998

Evolution of transcriptional regulatory elements within the promoter of a mammalian gene.

Transcription of the murine D7Rp2e gene is highly variable among species of the genus Mus, indicating that extensive modifications in the gene's regulatory elements have occurred during evolution. Since promoter regions are well known to harbor cis-acting information that controls gene transcription, we compared the sequence and function of the D7Rp2e promoter in several Mus species, with the goal of understanding the molecular mechanisms underlying the interspecies variations in expression. Three overlapping binding sites for nuclear factors (sites A, B, and C in proximal to distal order) were identified about 300 bp upstream of the transcriptional start site. The sequences of these sites differ between the species Mus domesticus and M. pahari, which exhibit distinct D7Rp2e expression phenotypes. Site A binds a factor called RPBF-I; sites B and C bind a distinct factor that is termed RPBF-II and is likely a member of the NF-I family of transcription factors. DNase I footprinting experiments with the M. domesticus promoter show that binding of RPBF-II at site B is very strong, while binding of RPBF-I and RPBF-II at sites A and C, respectively, is weak; in contrast, with the M. pahari promoter, factor binding at sites A and C is strong, while that at site B is weak. These differences in patterns of binding-site occupancy derive from changes in the affinities of individual sites for their cognate nuclear factors. Transient transfection experiments indicate that the M. pahari binding pattern is capable of repressing transcription of a linked reporter. Such repression may contribute to the differences in D7Rp2e expression between the two species. We suggest that the species-specific footprinting patterns represent the existence of a dynamic equilibrium between two states of nuclear factor binding, the nature of which can be modified during evolution to result in new patterns of gene transcription.

Animals↗

PubMed2006

Genomic inferences of the cis-regulatory nucleotide polymorphisms underlying gene expression differences between Drosophila melanogaster mating races.

Nucleotide sequence polymorphisms affecting gene expression occur in the regulatory region of genes (in cis) and elsewhere in the genome (in trans). Further study is required to weigh the relative importance of cis- and trans-acting mutations in mediating gene expression differences within and between species. Here, microarray hybridization experiments were used to isolate 363 gene expression differences between the female fly head transcriptomes of 2 Drosophila melanogaster strains. One strain (French) represented the cosmopolitan M mating race and the other strain (ZS30) represented the Z mating race derived from Zimbabwe, Africa. From chromosomal substitution strains engineered from the 2 strains, we inferred that the expression differences between M and Z alleles largely could be attributed to the genotype of the chromosomes where the differentially expressed genes were located, that is, cis-regulatory polymorphisms prominently influence gene expression differences between M and Z. The effects of trans-regulatory polymorphisms were apparent yet difficult to quantify. Results have implications for models of gene regulatory evolution as well as experimental studies trying to identify the nucleotide sequence polymorphisms underlying gene expression differences between Drosophila strains.

Animals↗

PubMed1995

Evolutionary, regulatory and mediation aspects of T.b. rhodesiense and its endemicity in Lambwe Valley, Kenya.

The transmission of the human African trypanosomiasis (HAT) infection, also known as human sleeping sickness, depends on environmental factors operating at the mega-, macro-, and micro-scale levels. However, at the latter level T.b. rhodesiense parasite undergoes metacyclic development processes, controlled by its evolution, regulatory and mediation factors. Selective pressures acting on host-parasite interactions are thought to influence the genetics of the parasite and its hosts. In retrospect, the phenotypic difference responsible for the change in fitness of the parasite is complicated, since natural variation in a phenotype may be maintained by frequency-dependent selection, with species-specific fitness dynamics. Although little evidence exists on aspects of mutualism o f trypanosomes, it is possible that synergistic interactions among pathogens may be involved in the complex of phenotype variations. This paper considers the underlying dynamics with reference to the endemicity of the infection in Lambwe Valley ecosystem.

Journal Article↗

PubMed2025

Interspecies Organoids Reveal Human-Specific Molecular Features of Dopaminergic Neuron Development and Vulnerability.

The disproportionate expansion of telencephalic structures during human evolution involved tradeoffs that imposed greater connectivity and metabolic demands on midbrain dopaminergic neurons. Despite the central role of dopaminergic neurons in human-enriched disorders, molecular specializations associated with human-specific features and vulnerabilities of the dopaminergic system remain unexplored. Here, we establish a phylogeny-in-a-dish approach to examine gene regulatory evolution by differentiating pools of human, chimpanzee, orangutan, and macaque pluripotent stem cells into ventral midbrain organoids capable of forming long-range projections, spontaneous activity, and dopamine release. We identify human-specific gene expression changes related to axonal transport of mitochondria and reactive oxygen species buffering and candidate cis- and trans-regulatory mechanisms underlying gene expression divergence. Our findings are consistent with a model of evolved neuroprotection in response to tradeoffs related to brain expansion and could contribute to the discovery of therapeutic targets and strategies for treating disorders involving the dopaminergic system.

Brain evolution↗

PubMed2006

Many genes in fish have species-specific asymmetric rates of molecular evolution.

BACKGROUND: Gene and genome duplication events increase the amount of genetic material that might then contribute to an increase in the genomic and phenotypic complexity of organisms during evolution. Thus, it has been argued that there is a relationship between gene copy number and morphological complexity and/or species diversity. This hypothesis implies that duplicated genes have subdivided or evolved novel functions compared to their pre-duplication proto-orthologs. Such a functional divergence might be caused by an increase in evolutionary rates in one ortholog, by changes in expression, regulatory evolution, insertion of repetitive elements, or due to positive Darwinian selection in one copy. We studied a set of 2466 genes that were present in Danio rerio, Takifugu rubripes, Tetraodon nigroviridis and Oryzias latipes to test (i) for forces of positive Darwinian selection; (ii) how frequently duplicated genes are retained, and (iii) whether novel gene functions might have evolved. RESULTS: 25% (610) of all investigated genes show significantly smaller or higher genetic distances in the genomes of particular fish species compared to their human ortholog than their orthologs in other fish according to relative rate tests. We identified 49 new paralogous pairs of duplicated genes in fish, in which one of the paralogs is under positive Darwinian selection and shows a significantly higher rate of molecular evolution in one of the four fish species, whereas the other copy apparently did not undergo adaptive changes since it retained the original rate of evolution. Among the genes under positive Darwinian selection, we found a surprisingly high number of ATP binding proteins and transcription factors. CONCLUSION: The significant rate difference suggests that the function of these rate-changed genes might be essential for the respective fish species. We demonstrate that the measurement of positive selection is a powerful tool to identify divergence rates of duplicated genes and that this method has the capacity to identify potentially interesting candidates for adaptive gene evolution.

Adenosine Triphosphate↗

PubMed2004

Rates of evolution of hybrid inviability in birds and mammals.

Almost 30 years ago, A. C. Wilson and colleagues presented results indicating that hybrid inviability between species evolves 10 times faster in mammals than in birds and frogs. Here I revisit this question for birds and mammals using modern molecular data (mitochondrial cytochrome b DNA) and a more phylogenetically appropriate statistical approach. My analyses confirm that diverging mammals lose the ability to form viable hybrids faster than birds. To explain the difference in rates of evolutionary loss of hybridization potential, Wilson and coworkers proposed that mammals have higher rates of regulatory evolution, causing higher probabilities of developmental incompatibilities between mammal species. I briefly discuss this and other potential explanations.

Animals↗

PubMed1998

[The nature of adaptive evolutionary changes: fitness and potential].

Ecological potential of an individual can be defined as its viability in the broad sense including the ability to reproduce in various environments. From the biological viewpoint, ecological potential as a fundamental property of an organism is more important than fitness in the genetic sense, which is estimated as the relative rate of reproduction. In essence, fitness reflects the level of implementation of the biological potential. In the process of evolution, regulatory selection results in an increase of fitness: selected forms reproduce more successfully as the population size increases. By contrast, individuals with high ecological potential are more advantageous when the population size decreases, because the probability of their survival in adverse environments is high. Thus, high levels of fitness and ecological potential are achieved via operation of different types of selection.

Adaptation, Physiological↗

PubMed2002

The evolution of developmental regulatory pathways.

Evolutionary analysis of the content of developmental regulatory pathways has been advanced by the publication of pairs of complete genome sequences from representative taxonomic groups. Annotation of the fission yeast, rice, and mouse genomes confirms that most regulatory families are shared among eukaryotes but also shows that certain gene families have restricted distributions. Theoretical advances in the past few years include development of the theory of scale-free networks, which provides a new framework in which to consider the connectivity and evolution of regulatory systems, and introduction of algorithms that use comparative data to enhance detection of transcriptional regulatory motifs.

Animals↗

PubMed2002

The evolution of DNA regulatory regions for proteo-gamma bacteria by interspecies comparisons.

The comparison of homologous noncoding DNA for organisms a suitable evolutionary distance apart is a powerful tool for the identification of cis regulatory elements for transcription and translation and for the study of how they assemble into functional modules. We have fit the three parameters of an affine global probabilistic alignment algorithm to establish the background mutation rate of noncoding sequence between E. coli and a series of gamma proteobacteria ranging from Salmonella to Vibrio. The lower bound we find to the neutral mutation rate is sufficiently high, even for Salmonella, that most of the conservation of noncoding sequence is indicative of selective pressures rather than of insufficient time to evolve. We then use a local version of the alignment algorithm combined with our inferred background mutation rate to assign a significance to the degree of local sequence conservation between orthologous genes, and thereby deduce a probability profile for the upstream regulatory region of all E. coli protein-coding genes. We recover 75%-85% (depending on significance level) of all regulatory sites from a standard compilation for E. coli, and 66%-85% of sigma sites. We also trace the evolution of known regulatory sites and the groups associated with a given transcription factor. Furthermore, we find that approximately one-third of paralogous gene pairs in E. coli have a significant degree of correlation in their regulatory sequence. Finally, we demonstrate an inverse correlation between the rate of evolution of transcription factors and the number of genes they regulate. Our predictions are available at http://www.physics.rockefeller.edu/([tilde-see text])siggia.

Algorithms↗

PubMed2005

Conservation and evolvability in regulatory networks: the evolution of ribosomal regulation in yeast.

Transcriptional modules of coregulated genes play a key role in regulatory networks. Comparative studies show that modules of coexpressed genes are conserved across taxa. However, little is known about the mechanisms underlying the evolution of module regulation. Here, we explore the evolution of cis-regulatory programs associated with conserved modules by integrating expression profiles for two yeast species and sequence data for a total of 17 fungal genomes. We show that although the cis-elements accompanying certain conserved modules are strictly conserved, those of other conserved modules are remarkably diverged. In particular, we infer the evolutionary history of the regulatory program governing ribosomal modules. We show how a cis-element emerged concurrently in dozens of promoters of ribosomal protein genes, followed by the loss of a more ancient cis-element. We suggest that this formation of an intermediate redundant regulatory program allows conserved transcriptional modules to gradually switch from one regulatory mechanism to another while maintaining their functionality. Our work provides a general framework for the study of the dynamics of promoter evolution at the level of transcriptional modules and may help in understanding the evolvability and increased redundancy of transcriptional regulation in higher organisms.

Computational Biology↗

PubMed2007

Comparison of diverged Hoxc8 early enhancer activities reveals modification of regulatory interactions at conserved cis-acting elements.

The Hoxc8 early enhancer that controls the initiation and establishment of Hoxc8 expression in the developing mouse embryo is found in different vertebrate lineages including mammals, birds and fish. Mouse and Fugu Hoxc8 early enhancers (200 bp) have diverged in the composition of elements located towards the 3' region. However, they share cis-acting elements A-E located in the 5' region. Mutations at these elements in the context of the mouse Hoxc8 early enhancer affect reporter gene expression in the posterior neural tube, somites and lateral plate mesoderm of day 9.5 mouse embryos. Here, we demonstrate that mutations introduced at the same elements but in the context of the Fugu Hoxc8 early enhancer had different consequences on the reporter gene expression in transgenic mouse embryos. Furthermore, in contrast to the mouse enhancer the Fugu enhancer does not utilize elements D and E in achieving posterior neural tube and somite expression. These results suggest that the diverged sequences prevent regulatory interactions at conserved cis-acting elements. We propose that divergent sequences modify regulatory interactions at conserved elements by providing a "contextual change". Our finding that the enhancer elements do not act in a unitary fashion but function in the context of the surrounding sequence brings a new dimension to the study of cis-regulatory evolution.

Animals↗

PubMed1998

Interelement selection in the regulatory region of the copia retrotransposon.

We report the results of an analysis of naturally occurring cis-regulatory variation within and between two families of the copia Drosophila long terminal repeat (LTR) retrotransposon. The copia 5' LTR and adjacent untranslated leader region (ULR) consists of a number of well-characterized sequence motifs which play a role in regulating expression of the element. In order to understand the evolutionary forces which may be responsible for generating and maintaining copia regulatory sequence variation, we have quantified levels of naturally occurring copia LTR-ULR nucleotide variation and subjected the data to a series of tests of neutrality. Our analysis indicates that the copia LTR-ULR has been subject to negative purifying selection within families and positive adaptive selection between families. We discuss these findings with respect to the regulatory evolution of retrotransposons and the phenomenon of interelement selection.

5' Untranslated Regions↗