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PubMed2006

Repeated morphological evolution through cis-regulatory changes in a pleiotropic gene.

The independent evolution of morphological similarities is widespread. For simple traits, such as overall body colour, repeated transitions by means of mutations in the same gene may be common. However, for more complex traits, the possible genetic paths may be more numerous; the molecular mechanisms underlying their independent origins and the extent to which they are constrained to follow certain genetic paths are largely unknown. Here we show that a male wing pigmentation pattern involved in courtship display has been gained and lost multiple times in a Drosophila clade. Each of the cases we have analysed (two gains and two losses) involved regulatory changes at the pleiotropic pigmentation gene yellow. Losses involved the parallel inactivation of the same cis-regulatory element (CRE), with changes at a few nucleotides sufficient to account for the functional divergence of one element between two sibling species. Surprisingly, two independent gains of wing spots resulted from the co-option of distinct ancestral CREs. These results demonstrate how the functional diversification of the modular CREs of pleiotropic genes contributes to evolutionary novelty and the independent evolution of morphological similarities.

Animals↗

PubMedDate not supplied

Evolution of catalytic and regulatory sites in phosphorylases.

Glycogen phosphorylase (E.C.2.4.1.1) was the first enzyme shown to be regulated by allosteric effectors and by protein phosphorylation. Transcriptional control of bacterial phosphorylases further extends the range of regulatory mechanisms by which phosphorylases contribute to the control of carbohydrate metabolism. Despite their regulatory differences, all known phosphorylases share catalytic and structural properties and a strongly conserved pyridoxal-5'-phosphate binding site; this makes phosphorylases highly attractive for investigations into the evolution of regulatory mechanisms. The primary and tertiary structure of rabbit muscle phosphorylase has been determined completely. Recently, comparable amino acid sequences from plants and bacteria have been resolved. Here we report the sequence of 687 amino acids of Escherichia coli maltodextrin phosphorylase, deduced from a cloned malP gene sequence. Alignment of animal and bacterial phosphorylase sequences shows strong homology (48%) throughout 91% of the polypeptide chain enclosing the extrinsic catalytic region. Within this region, structural homology identifies a presumed phosphate-binding site from which the allosteric 5' AMP binding site of rabbit muscle phosphorylase might have developed. From the decreased alignment at the N-terminus and the presence of additional residues compared with bacterial phosphorylases, we conclude that the regulatory sequences that also carry the phosphorylation site in the muscle enzyme were joined to a presumed ancestral precursor gene by gene fusion after separation of the eukaryotic and prokaryotic lines of descent.

Adenosine Monophosphate↗

PubMedDate not supplied

Regulatory punctuated equilibrium and convergence in the evolution of developmental pathways in direct-developing sea urchins.

We made hybrid crosses between closely and distantly related sea urchin species to test two hypotheses about the evolution of gene regulatory systems in the evolution of ontogenetic pathways and larval form. The first hypothesis is that gene regulatory systems governing development evolve in a punctuational manner during periods of rapid morphological evolution but are relatively stable over long periods of slow morphological evolution. We compared hybrids between direct and indirect developers from closely and distantly related families. Hybrids between eggs of the direct developer Heliocidaris erythrogramma and sperm of the 4-million year distant species H. tuberculata, an indirect developer, restored feeding larval structures and paternal gene expression that were lost in the evolution of the direct-developing maternal parent. Hybrids resulting from the cross between eggs of H. erythrogramma and sperm of the 40-million year distant indirect-developer Pseudoboletia maculata are strikingly similar to hybrids between the congeneric hybrids. The marked similarities in ontogenetic trajectory and morphological outcome in crosses of involving either closely or distantly related indirect developing species indicates that their regulatory mechanisms interact with those of H. erythrogramma in the same way, supporting remarkable conservation of molecular control pathways among indirect developers. Second, we tested the hypothesis that convergent developmental pathways in independently evolved direct developers reflect convergence of the underlying regulatory systems. Crosses between two independently evolved direct-developing species from two 70-million year distant families, H. erythrogramma and Holopneustes purpurescens, produced harmoniously developing hybrid larvae that maintained the direct mode of development and did not exhibit any obvious restoration of indirect-developing features. These results are consistent with parallel evolution of direct-developing features in these two lineages.

Animals↗

PubMed2004

Conservation and evolution of cis-regulatory systems in ascomycete fungi.

Relatively little is known about the mechanisms through which gene expression regulation evolves. To investigate this, we systematically explored the conservation of regulatory networks in fungi by examining the cis-regulatory elements that govern the expression of coregulated genes. We first identified groups of coregulated Saccharomyces cerevisiae genes enriched for genes with known upstream or downstream cis-regulatory sequences. Reasoning that many of these gene groups are coregulated in related species as well, we performed similar analyses on orthologs of coregulated S. cerevisiae genes in 13 other ascomycete species. We find that many species-specific gene groups are enriched for the same flanking regulatory sequences as those found in the orthologous gene groups fromS. cerevisiae, indicating that those regulatory systems have been conserved in multiple ascomycete species. In addition to these clear cases of regulatory conservation, we find examples of cis-element evolution that suggest multiple modes of regulatory diversification, including alterations in transcription factor-binding specificity, incorporation of new gene targets into an existing regulatory system, and cooption of regulatory systems to control a different set of genes. We investigated one example in greater detail by measuring the in vitro activity of the S. cerevisiae transcription factor Rpn4p and its orthologs from Candida albicans and Neurospora crassa. Our results suggest that the DNA binding specificity of these proteins has coevolved with the sequences found upstream of the Rpn4p target genes and suggest that Rpn4p has a different function in N. crassa.

Amino Acid Motifs↗

PubMed2006

Gene regulatory networks and the evolution of animal body plans.

Development of the animal body plan is controlled by large gene regulatory networks (GRNs), and hence evolution of body plans must depend upon change in the architecture of developmental GRNs. However, these networks are composed of diverse components that evolve at different rates and in different ways. Because of the hierarchical organization of developmental GRNs, some kinds of change affect terminal properties of the body plan such as occur in speciation, whereas others affect major aspects of body plan morphology. A notable feature of the paleontological record of animal evolution is the establishment by the Early "Cambrian of virtually all phylum-level body plans. We identify a class of GRN component, the kernels" of the network, which, because of their developmental role and their particular internal structure, are most impervious to change. Conservation of phyletic body plans may have been due to the retention since pre-Cambrian time of GRN kernels, which underlie development of major body parts.

Adaptation, Biological↗

PubMed2006

Evolution of cis-regulatory sequence and function in Diptera.

Cis-regulatory sequences direct patterns of gene expression essential for development and physiology. Evolutionary changes in these sequences contribute to phenotypic divergence. Despite their importance, cis-regulatory regions remain one of the most enigmatic features of the genome. Patterns of sequence evolution can be used to identify cis-regulatory elements, but the power of this approach depends upon the relationship between sequence and function. Comparative studies of gene regulation among Diptera reveal that divergent sequences can underlie conserved expression, and that expression differences can evolve despite largely similar sequences. This complex structure-function relationship is the primary impediment for computational identification and interpretation of cis-regulatory sequences. Biochemical characterization and in vivo assays of cis-regulatory sequences on a genomic-scale will relieve this barrier.

Animals↗

PubMed2003

Evolution of cis-regulatory elements in duplicated genes of yeast.

An increasing number of studies report that functional divergence in duplicated genes is accompanied by gene expression changes, although the evolutionary mechanism behind this process remains unclear. Our genomic analysis on the yeast Saccharomyces cerevisiae shows that the number of shared regulatory motifs in the duplicates decreases with evolutionary time, whereas the total number of regulatory motifs remains unchanged. Moreover, genes with numerous paralogs in the yeast genome do not have especially low number of regulatory motifs. These findings indicate that degenerative complementation is not the sole mechanism behind expression divergence in yeast. Moreover, we found some evidence for the action of positive selection on cis-regulatory motifs after gene duplication. These results suggest that the evolution of functional novelty has a substantial role in yeast duplicate gene evolution.

Evolution, Molecular↗

PubMed2003

Evolution of cis-regulatory regions versus codifying regions.

Efforts to understand the genetic basis of evolutionary change have concentrated on proteins and their encoding DNA sequences. These studies have brought to light patterns and processes at the nucleotide level, yet the complex functional relationships between genetic variants and phenotypes remain poorly known. The realization that even a complete description of proteins and the effects of their activity will not suffice to understand the conditions under which they are time- and tissue-specifically expressed or repressed during development has refocused attention on cis-regulatory regions. In particular, promoter sequences are thought to hold the key for understanding the evolution of phenotypic differences between species. This is because of their complex organization into independent modules such that, unlike coding sequences in which mutations affect protein function every time the protein is expressed, mutations in cis-regulatory sequences may have minor or no pleiotropic effects. Complex information-encoding makes cis-regulatory regions poorly amenable to comparative methods designed for coding sequences. Some general conclusions are emerging as to how genetic variation is distributed across regulatory networks and the processes modulating the structure of this variation. We bring into this emerging scenario several recent findings pointing to different ways in which spliceosomal introns, pseudogenes and patterns of point mutation can be active players for the evolution of novel transcriptional profiles.

Animals↗

PubMed2003

Evolution by gene duplication revisited: differentiation of regulatory elements versus proteins.

For evolution by gene duplication, differentiation of both regulatory elements and proteins is important. Particularly the former is thought to have large effects on morphological evolution, since differential expression of genes is essential for development. In this report, recent knowledge on regulatory elements is reviewed that is relevant to the population genetics aspects of gene duplication. Regulatory elements usually consist of multiple binding sites of two or more transcription factors. The amount of gene product is quantitatively regulated, and is thought to be subject to stabilizing selection. The intensity of stabilizing selection depends upon the level of constraint imposed by regulatory networks. Gene duplication has significant effects on stabilizing selection via perturbation of gene expression. It is pointed out that constraints coming from regulatory networks are most important for survival of duplicate genes, and that both drift and selection are at work in the process of acquisition of new gene expression and function.

Evolution, Molecular↗

PubMed1998

Analysis of bHLH and MYB domain proteins: species-specific regulatory differences are caused by divergent evolution of target anthocyanin genes.

The regulatory anthocyanin loci, an1, an2, an4 and an11 of Petunia hybrida, and r and c1 from Zea mays, control transcription of different sets of target genes. Both an2 and c1 encode a MYB-type protein. This study reports the isolation of a P. hybrida gene, jaf13, encoding a basic helix-loop-helix protein that, on the basis of sequence homology and intron/exon structure, represents the P. hybrida orthologue of the Z. mays r genes. Ectopic expression of an2 and jaf13 is sufficient for activation of the dihydroflavonol 4-reductase-A (dfrA) promoter and enhanced pigment accumulation in P. hybrida. This indicates that an2 and jaf13 play a key role in determining the tissue-specific expression pattern of structural genes. However, because chalcone synthase (chs) and flavanone-3-hydroxylase (f3h) are not activated, the pattern of pigmentation is not fundamentally altered. Expression of an2 in Z. mays complements a mutation in pl, a c1 paralogue, indicating that an2 activates a wider set of target genes in this host. Transient expression assays in Z. mays and P. hybrida tissues showed that C1 and R or AN2 and JAF13 can activate the promoter of the c2 gene, encoding Z. mays CHS, but not the chsA promoter from P. hybrida. These results indicate that regulatory anthocyanin genes are conserved between species and that divergent evolution of the target gene promoters is responsible for the species-specific differences in regulatory networks.

Amino Acid Sequence↗

PubMed2004

Creation of cis-regulatory elements during sea urchin evolution by co-option and optimization of a repetitive sequence adjacent to the spec2a gene.

The creation, preservation, and degeneration of cis-regulatory elements controlling developmental gene expression are fundamental genome-level evolutionary processes about which little is known. Here, we identify critical differences in cis-regulatory elements controlling the expression of the sea urchin aboral ectoderm-specific spec genes. We found multiple copies of a repetitive sequence element termed RSR in genomes of species within the Strongylocentrotidae family, but RSRs were not detected in genomes of species outside Strongylocentrotidae. spec genes in Strongylocentrotus purpuratus are invariably associated with RSRs, and the spec2a RSR functioned as a transcriptional enhancer and displayed greater activity than did spec1 or spec2c RSRs. Single-base pair differences at two cis-regulatory elements within the spec2a RSR increased the binding affinities of four transcription factors, SpCCAAT-binding factor at one element and SpOtx, SpGoosecoid, and SpGATA-E at another. The cis-regulatory elements to which these four factors bound were recent evolutionary acquisitions that acted to either activate or repress transcription, depending on the cell type. These elements were found in the spec2a RSR ortholog in Strongylocentrotus pallidus but not in RSR orthologs of Strongylocentrotus droebachiensis or Hemicentrotus pulcherrimus. Our results indicated that a dynamic pattern of cis-regulatory element evolution exists for spec genes despite their conserved aboral ectoderm expression.

Animals↗

PubMed2003

Genes that determine flower color: the role of regulatory changes in the evolution of phenotypic adaptations.

A central goal of evolutionary genetics is to trace the causal pathway between mutations at particular genes and adaptation at the phenotypic level. The proximate objective is to identify adaptations through the analysis of molecular sequence data from specific candidate genes or their regulatory elements. In this paper, we consider the molecular evolution of floral color in the morning glory genus (Ipomoea) as a model for relating molecular and phenotypic evolution. To begin, flower color variation usually conforms to simple Mendelian transmission, thus facilitating genetic and molecular analyses. Population genetic studies of flower color polymorphisms in the common morning glory (Ipomoea purpurea) have shown that some morphs are subject to complex patterns of selection. Striking differences in floral color and morphology are also associated with speciation in the genus Ipomoea. The molecular bases for these adaptive shifts can be dissected because the biosynthetic pathways that determine floral pigmentation are well understood and many of the genes of flavonoid biosynthesis have been isolated and extensively studied. We present a comparative analysis of the level of gene expression in Ipomoea for several key genes in flavonoid biosynthesis. Specifically we ask: how frequently are adaptive shifts in flower color phenotypes associated with changes in regulation of gene expression versus mutations in structural genes? The results of this study show that most species differences in this crucial phenotype are associated with changes in the regulation of gene expression.

Adaptation, Physiological↗

PubMed2006

Proceedings of the SMBE Tri-National Young Investigators' Workshop 2005. Positional conservation of clusters of overlapping promoter-like sequences in enterobacterial genomes.

The selective mechanisms operating in regulatory regions of bacterial genomes are poorly understood. We have previously shown that, in most bacterial genomes, regulatory regions contain high densities of sigma70 promoter-like signals that are significantly above the densities detected in nonregulatory genomic regions. In order to investigate the molecular evolutionary forces that operate in bacterial regulatory regions and how they affect the observed redundancy of promoter-like signals, we have undertaken a comparative analysis across the completely sequenced genomes of enteric gamma-proteobacteria. This analysis detects significant positional conservation of promoter-like signal clusters across enterics, some times in spite of strong primary sequence divergence. This suggests that the conservation of the nature and exact position of specific nucleotides is not necessarily the priority of selection for maintaining the transcriptional function in these bacteria. We have further characterized the structural conservation of the regulatory regions of dnaQ and crp across all enterics. These two regions differ in essentiality and mode of regulation, the regulation of crp being more complex and involving interactions with several transcription factors. This results in substantially different modes of evolution, with the dnaQ region appearing to evolve under stronger purifying selection and the crp region showing the likely effects of stabilizing selection for a complex pattern of gene expression. The higher flexibility of the crp region is consistent with the observed less conservation of global regulators in evolution. Patterns of regulatory evolution are also found to be markedly different in endosymbiotic bacteria, in a manner consistent with regulatory regions suffering some level of degradation, as has been observed for many other characters in these genomes. Therefore, the mode of evolution of bacterial regulatory regions appears to be highly dependent on both the lifestyle of the bacterium and the specific regulatory requirements of different genes. In fact, in many bacteria, the mode of evolution of genes requiring significant physiological adaptability in expression levels may follow patterns similar to those operating in the more complex regulatory regions of eukaryotic genomes.

Amino Acid Sequence↗

PubMed2006

Gene regulatory networks in the evolution and development of the heart.

The heart, an ancient organ and the first to form and function during embryogenesis, evolved by the addition of new structures and functions to a primitive pump. Heart development is controlled by an evolutionarily conserved network of transcription factors that connect signaling pathways with genes for muscle growth, patterning, and contractility. During evolution, this ancestral gene network was expanded through gene duplication and co-option of additional networks. Mutations in components of the cardiac gene network cause congenital heart disease, the most common human birth defect. The consequences of such mutations reveal the logic of organogenesis and the evolutionary origins of morphological complexity.

Animals↗

PubMedDate not supplied

Origin of a gene regulatory mechanism in the evolution of echinoderms.

A rich diversity of ancient sea urchin lineages survives to the present. These include several advanced orders as well as the cidaroids, which represent the group ancestral to all other sea urchins. Here we show that all advanced groups of sea urchins examined possess in their eggs a class of maternal messenger RNA (mRNA) encoded by the evolutionarily highly conserved alpha-subtype histone genes. The maternal histone mRNAs are unique in their time of accumulation in oogenesis, their localization in the egg nucleus and their delayed timing of translation after fertilization. Cidaroid sea urchins as well as other echinoderm classes, such as starfish and sea cucumbers, possess the genes but do not have maternal alpha-subtype histone mRNAs in their eggs. Thus, although all the echinoderms examined transcribe alpha-subtype histone genes during embryogenesis, the expression of these genes as maternal mRNAs is confined to advanced sea urchins. The fossil record allows us to pinpoint the evolution of this mode of expression of alpha-histone genes to the time of the splitting of advanced sea urchin lineages from the ancestral cidaroids in a radiation which occurred in a relatively brief interval of time approximately 190-200 Myr ago. The origin of a unique gene regulatory mechanism can thus be correlated with a set of macroevolutionary events.

Animals↗

PubMed2006

Evolution of candidate transcriptional regulatory motifs since the human-chimpanzee divergence.

BACKGROUND: Despite the recent completion of the chimpanzee genome project, few functionally significant sequence differences between humans and chimpanzees have thus far been identified. Alteration in transcriptional regulatory mechanisms represents an important platform for evolutionary change, suggesting that a significant proportion of functional human-chimpanzee sequence differences may affect regulatory elements. RESULTS: To explore this hypothesis, we performed genome-wide identification of conserved candidate transcription-factor binding sites that have evolved since the divergence of humans and chimpanzees. Analysis of candidate transcription-factor binding sites conserved between mouse and chimpanzee yet absent in human indicated that loss of candidate transcription-factor binding sites in the human lineage was not random but instead correlated with the biologic functions of associated genes. CONCLUSION: Our data support the notion that changes in transcriptional regulation have contributed to the recent evolution of humans. Moreover, genes associated with mutated candidate transcription-factor binding sites highlight potential pathways underlying human-chimpanzee divergence.

Animals↗

PubMed2025

Genome-Wide Mining of lncRNAs Reveals Their Potential Regulatory Role in the Evolution of Viviparity.

Reproduction in vertebrates usually involves egg-laying (oviparity) or live-bearing (viviparity). Oviparity is the ancestral trait from which viviparity has independently evolved more than 100 times in squamate reptiles. This transition involves a series of physiological and structural changes, including the degeneration of eggshell and the evolution of a placenta and differences in the temporal and spatial expression patterns of some functional genes that drive the structural transformation. Long non-coding RNAs (lncRNAs) play important roles in the regulation of gene expression, yet it remains unclear whether they participate in gene expression shifts during the transition from oviparity to viviparity, and if so how. Therefore, we employ deep mining to identify novel lncRNAs of a closely related oviparous-viviparous pair of lizards (Phrynocephalus przewalskii and P. vlangalii). We construct cis- and trans-regulatory networks between lncRNAs and target genes using the transcriptomic data of oviduct or uteri tissues across reproductive periods. Results show that lncRNAs that regulate eggshell gland developmental genes in the oviparous lizard are lost or less expressed in the viviparous lizard. A number of lncRNAs involved in the regulation of placental development and embryo attachment in viviparous species have no orthologs in oviparous species, and others show little or no expression. Accordingly, lncRNAs may play important regulatory roles in the physiological and structural changes in the transition from oviparity to viviparity. These results open doors to the further elucidation of genetic regulatory networks.

Animals↗

PubMed2026

Comparative analysis of conserved non-coding elements identifies gene regulatory networks rewired during the water-to-land transition in vertebrates.

The conquest of land by vertebrates has been a pivotal moment in evolutionary history. Adapting to the new habitats necessitated numerous changes in vertebrate anatomy and physiology, creating an enduring imprint on the developmental gene regulatory networks (GRNs) of tetrapods. The increase of high-quality genomic resources over the past decade has made it possible to study the genomic legacy of the water-to-land transition. While much attention has been given to the highly conserved non-coding elements (CNEs) of the genome that share high levels of similarity across evolutionarily diverged clades, recent evidence suggests that perhaps comparable attention should be given to "missing" CNE-s, conserved sequence patches present in extant stem gnathostomes and actinopterygian fishes that have become undetectable in tetrapods during the adaptation to terrestrial life, whether through true sequence loss or divergence beyond alignability. These sequences could help us reveal the relaxation of certain developmental constraints, related to the aquatic lifestyle, that made reaching new adaptive peaks in the developmental landscape possible. In this paper, we search for such CNEs and characterize them in comparison with pan-Gnathostome CNEs, using the zebrafish (Danio rerio) genome as a reference. Our results suggest that the rewiring of developmental networks related to pigmentation and muscle structure formation has left the largest genomic imprint. We also find that components of canonical Wnt and Hedgehog signalling, are enriched among CNEs retained in fish.

cis-regulatory evolution↗