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Homeotic genes and the evolution of arthropods and chordates.

Clusters of homeotic genes sculpt the morphology of animal body plans and body parts. Different body patterns may evolve through changes in homeotic gene number, regulation or function. Recent evidence suggests that homeotic gene clusters were duplicated early in vertebrate evolution, but the generation of arthropod and tetrapod diversity has largely involved regulatory changes in the expression of conserved arrays of homeotic genes and the evolution of interactions between homeotic proteins and the genes they regulate.

Animals↗

Evolution of yellow gene regulation and pigmentation in Drosophila.

BACKGROUND: Changes in developmental gene expression are central to phenotypic evolution, but the genetic mechanisms underlying these changes are not well understood. Interspecific differences in gene expression can arise from evolutionary changes in cis-regulatory DNA and/or in the expression of trans-acting regulatory proteins, but few case studies have distinguished between these mechanisms. Here, we compare the regulation of the yellow gene, which is required for melanization, among distantly related Drosophila species with different pigment patterns and determine the phenotypic effects of divergent Yellow expression. RESULTS: Yellow expression has diverged among D. melanogaster, D. subobscura, and D. virilis and, in all cases, correlates with the distribution of black melanin. Species-specific Yellow expression patterns were retained in D. melanogaster transformants carrying the D. subobscura and D. virilis yellow genes, indicating that sequence evolution within the yellow gene underlies the divergence of Yellow expression. Evolutionary changes in the activity of orthologous cis-regulatory elements are responsible for differences in abdominal Yellow expression; however, cis-regulatory element evolution is not the sole cause of divergent Yellow expression patterns. Transformation of the D. melanogaster yellow gene into D. virilis altered its expression pattern, indicating that trans-acting factors that regulate the D. melanogaster yellow gene have also diverged between these two species. Finally, we found that the phenotypic effects of evolutionary changes in Yellow expression depend on epistatic interactions with other genes. CONCLUSIONS: Evolutionary changes in Yellow expression correlate with divergent melanin patterns and are a result of evolution in both cis- and trans-regulation. These changes were likely necessary for the divergence of pigmentation, but evolutionary changes in other genes were also required.

Animals↗

Evolution of homeotic gene regulation and function in flies and butterflies.

It has been proposed that the evolution of homeotic genes parallels, and to some degree directs, the evolution of segment diversity in the myriapod-insect lineage. But the discovery of discrete Antennapedia complex (ANT-C) and bithorax complex (BX-C) gene members in crustacea, chelicerates, annelids and various insects, as well as in vertebrates, indicates that the expansion and diversification of homeotic genes preceded the diversification of arthropods and insects. How, then, have these genes influenced the evolution of body plans? To address this question, we now examine homeotic gene expression and regulation in butterflies (Lepidoptera), which, unlike flies, possess larval abdominal limbs and two pairs of wings. We show that the difference in larval limb number between these insects results from striking changes in BX-C gene regulation in the butterfly abdomen, and we deduce that the wing-patterning genes regulated by Ultrabithorax have diverged in the course of butterfly and fly evolution. These findings have general implications for the role of homeotic genes in animal evolution.

Amino Acid Sequence↗

Diversification, loss, and virulence gains of the major effector AvrStb6 during continental spread of the wheat pathogen Zymoseptoria tritici.

Interactions between plant pathogens and their hosts are highly dynamic and mainly driven by pathogen effectors and plant receptors. Host-pathogen co-evolution can cause rapid diversification or loss of pathogen genes encoding host-exposed proteins. The molecular mechanisms that underpin such sequence dynamics remains poorly investigated at the scale of entire pathogen species. Here, we focus on AvrStb6, a major effector of the global wheat pathogen Zymoseptoria tritici, evolving in response to the cognate receptor Stb6, a resistance widely deployed in wheat. We comprehensively captured effector gene evolution by analyzing a global thousand-genome panel using reference-free sequence analyses. We found that AvrStb6 has diversified into 59 protein isoforms with a strong association to the pathogen spreading to new continents. Across Europe, we found the strongest differentiation of the effector consistent with high rates of Stb6 deployment. The AvrStb6 locus showed also a remarkable diversification in transposable element content with specific expansion patterns across the globe. We detected AvrStb6 gene losses and evidence for transposable element-mediated disruptions. We used virulence datasets of genome-wide association mapping studies to predict virulence changes across the global panel. Genomic predictions suggested marked increases in virulence on Stb6 cultivars concomitant with the spread of the pathogen to Europe and the subsequent spread to further continents. Finally, we genotyped French bread wheat cultivars for Stb6 and monitored resistant cultivar deployment concomitant with AvrStb6 evolution. Taken together, our data provides a comprehensive view of how a rapidly diversifying effector locus can undergo large-scale sequence changes concomitant with gains in virulence on resistant cultivars. The analyses highlight also the need for large-scale pathogen sequencing panels to assess the durability of resistance genes and improve the sustainability of deployment strategies.

Ascomycota↗

Relative developmental success of interspecific Lepomis hybrids as an estimate of gene regulatory divergence between species.

The developmental success of interspecific Lepomis hybrids is used as an index of gene regulatory divergence between the green sunfish, L. cyanellus, and each of three other parental species, longear sunfish, L. megalotis, warmouth, L. gulosus, and bluegill, L. macrochirus. This gene regulatory divergence is compared to the degree of structural gene divergence among these four species (genetic distance [Nei, '78], D, ranged from 0.206 to 0.586). The developmental success of the hybrid embryos at the level of morphogenesis was higher than expected from the genetic distance between the parental species. The rates of morphogenesis of the hybrid embryos were the same as that for the green sunfish embryos. The percentage of embryos that hatched was relatively high in all crosses. However, two of the hybrid crosses resulted in enhanced percentages of hatched embryos. Slight increases in the extent of morphological abnormalities were observed in hybrids from crosses between more distantly related parental species. The schedules and levels of enzyme locus expression of the hybrids, assessed spectrophotometrically and electrophoretically for nine enzyme systems (encoded in a total of 14 loci), were different from each other and from those of the green sunfish embryos. Alterations in the time of first enzyme appearance and in the time of first increase in enzyme activity in the developing hybrid embryos were not correlated with genetic distance between parental species. However, the extents of alteration of enzyme activities over the entire period of hybrid embryogenesis were correlated with the genetic distance. We attribute the morphological and molecular anomalies observed in the hybrids to gene regulatory incompatibilities between species. Although the exact number of mutational differences and their relative developmental impacts are not known, some inferences can be drawn about the degree of divergence in gene regulation between species. It appears that an uncoupling of the rates of structural and regulatory gene evolution can occur between species of some taxa, an observation that has implications for the roles of gene regulatory differences in organismic evolution.

Animals↗

Hox genes and the evolution of diverse body plans.

Homeobox genes encode transcription factors that carry out diverse roles during development. They are widely distributed among eukaryotes, but appear to have undergone an extensive radiation in the earliest metazoa, to generate a range of homeobox subclasses now shared between diverse metazoan phyla. The Hox genes comprise one of these subfamilies, defined as much by conserved chromosomal organization and expression as by sequence characteristics. These Hox genes act as markers of position along the antero-posterior axis of the body in nematodes, arthropods, chordates, and by implication, most other triploblastic phyla. In the arthropods this role is visualized most clearly in the control of segment identity. Exactly how Hox genes control the structure of segments is not yet understood, but their differential deployment between segments provides a model for the basis of segment diversity. Within the arthropods, distantly related taxonomic groups with very different body plans (insects, crustaceans) may share the same set of Hox genes. The expression of these Hox genes provides a new character to define the homology of different body regions. Comparisons of Hox gene deployment between insects and a branchiopod crustacean suggest a novel model for the derivation of the insect body plan.

Animals↗

The complete intron/exon structure of Ephydatia mülleri fibrillar collagen gene suggests a mechanism for the evolution of an ancestral gene module.

We have completed the analysis of a genomic clone, G238, that contains most of the coding region of the sponge COLF1 fibrillar collagen gene. The main triple helical domain is encoded by 31 exons. Except for the 5' junction exon and the two last 3' exons (126 and 18 base pairs), all these exons are related to a 54-bp unit and begin with an intact glycine codon. A good correlation can be made between this sponge gene and a vertebrate fibrillar collagen gene, revealing the high conservation of the members of this family during evolution. The reconstitution of an ancestral collagen gene can be made by considering all the exon/intron junctions of these genes. We suggest that such an ancestral gene arose from multiple duplications of a 54-bp exon and a (54 + 45)-bp module.

Amino Acid Sequence↗

Phylogenomic analysis and expression patterns of large Maf genes in Xenopus tropicalis provide new insights into the functional evolution of the gene family in osteichthyans.

We have performed an exhaustive characterization of the large Maf family of basic leucine zipper transcription factors in vertebrates using the genome data available, and studied the embryonic expression patterns of the four paralogous genes thus identified in Xenopus tropicalis. Our phylogenetic analysis shows that, in osteichthyans, the large Maf family contains four orthology classes, MafA, MafB, c-Maf and Nrl, which have emerged in vertebrates prior to the split between actinopterygians and sarcopterygians. It leads to the unambiguous assignment of the Xenopus laevis XLmaf gene, previously considered a MafA orthologue, to the Nrl class, the identification of the amphibian MafA and c-Maf orthologues and the identification of the zebrafish Nrl gene. The four X. tropicalis paralogues display partially redundant but nevertheless distinct expression patterns in the somites, developing hindbrain, pronephros, ventral blood island and lens. Comparisons with the data available in the mouse, chick and zebrafish show that these large Maf expression territories are highly conserved among osteichthyans but also highlight a number of differences in the timing of large Maf gene expression, the precise extent of some labelled territories and the combinations of paralogues transcribed in some organs. In particular, the availability of robust phylogenies leads to a reinterpretation of previous expression pattern comparisons, suggesting an important part for function shuffling within the gene family in the developing lens. These data highlight the importance of exhaustive characterizations of gene families for comparative analyses of the genetic mechanisms, which control developmental processes in vertebrates.

Animals↗

The genesis and evolution of homeobox gene clusters.

Once called the 'Rosetta stone' of developmental biology, the homeobox continues to fascinate both evolutionary and developmental biologists. The birth of the homeotic, or Hox, gene cluster, and its subsequent evolution, has been crucial in mediating the major transitions in metazoan body plan. Comparative genomics studies indicate that the more recently discovered ParaHox and NK clusters were linked to the Hox cluster early in evolution, and that together they constituted a 'megacluster' of homeobox genes that conspicuously contributed to body-plan evolution.

Evolution, Molecular↗

Cytosine methylation and the fate of CpG dinucleotides in vertebrate genomes.

The dinucleotide CpG is a "hotspot" for mutation in the human genome as a result of (1) the modification of the 5' cytosine by cellular DNA methyltransferases and (2) the consequent high frequency of spontaneous deamination of 5-methyl cytosine (5mC) to thymidine. DNA methylation thus contributes significantly, albeit indirectly, to the incidence of human genetic disease. We have attempted to estimate for the first time the in vivo rate of deamination of 5mC from the measured rate of 5mC deamination in vitro and the known error frequency of the cellular G/T mismatch-repair system. The accuracy and utility of this estimate (md) was then assessed by comparison with clinical data, and an improved estimate of md (1.66 X 10(-16) s-1) was derived. Comparison of the CpG mutation rates exhibited by globin gene and pseudogene sequences from human, chimpanzee and macaque provided further estimates of md, all of which were consistent with the first. Use of this value in a mathematical model then permitted the estimation of the length of time required to produce the level of "CpG suppression" currently found in the "bulk DNA" of vertebrate genomes. This time span, approximately 450 million years, corresponds closely to the estimated time since the emergence and adaptive radiation of the vertebrates and thus coincides with the probable advent of heavily methylated genomes. An accurate estimate of the 5mC deamination rate is important not only for clinical medicine but also for studies of gene evolution. Our data suggest both that patterns of vertebrate gene methylation may be comparatively stable over relatively long periods of evolutionary time, and that the rate of CpG deamination can, under certain limited conditions, serve as a "molecular clock".

Animals↗

Repetitive DNA sequences located in the central region of the human mdr1 (multidrug resistance) gene may account for a gene fusion event during its evolution.

The mdr1 gene, first member of the human multidrug-resistance gene family, is a major gene involved in cellular resistance to several drugs used in anticancer chemotherapy. Its product, the drug-excreting P-glycoprotein, shows a bipartite structure formed by two similar adjacent halves. According to one hypothesis, the fusion of two related ancestral genes during evolution could have resulted in this structure. The DNA sequence analysis of the introns located in the region connecting the two halves of the human mdr1 gene revealed a highly conserved poly(CA).poly (TG) sequence in intron 15 and repeated sequences of the Alu family in introns 14 and 17. These repeated sequences most likely represent "molecular fossils" of ancient DNA elements which were involved in such a recombination event.

Base Sequence↗

An intron in the thymidylate synthase gene of Bacillus bacteriophage beta 22: evidence for independent evolution of a gene, its group I intron, and the intron open reading frame.

The thymidylate synthase gene (thy) (EC 2.1.1.45) of Bacillus subtilis bacteriophage beta 22 has a self-splicing, group I intron inserted into a highly conserved region of the coding sequence. The intron is very similar to one that is inserted 21 bp further downstream in the homologous thymidylate synthase gene (td) of Escherichia coli bacteriophage T4. In contrast, the amino acid sequences of the bacteriophage thymidylate synthases are highly divergent. The beta 22 intron has a fragmentary open reading frame (ORF) that encodes a putative helix-turn-helix DNA-binding motif, similar to one at the carboxyl terminus of the homing endonuclease (I-TevI) encoded by the T4 td intron. The td ORF and the thy ORF fragments are inserted into different regions of their respective intron structures. These results suggest that the thymidylate synthase genes, their introns, and their respective intron-ORFs all have separate evolutionary histories and that the acquisition of the intron could not have occurred by a simple homing event.

Amino Acid Sequence↗

SEGE: A database on 'intron less/single exonic' genes from eukaryotes.

UNLABELLED: Eukaryotes have both 'intron containing' and 'intron less' genes. Several databases are available for 'intron containing' genes in eukaryotes. In this note, we describe a database for 'intron less' genes from eukaryotes. 'Intron less' eukaryotic genes having prokaryotic architecture will help to understand gene evolution in a much simpler way unlike 'intron containing' genes. AVAILABILITY: SEGE is available at http://intron.bic.nus.edu.sg/seg/ CONTACT: mmeena@ntu.edu.sg

Animals↗

Rampant horizontal transfer and duplication of rubisco genes in eubacteria and plastids.

Previous work has shown that molecular phylogenies of plastids, cyanobacteria, and proteobacteria based on the rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase) genes rbcL and rbcS are incongruent with molecular phylogenies based on other genes and are also incompatible with structural and biochemical information. Although it has been much speculated that this is the consequence of a single horizontal gene transfer (of a proteobacterial or mitochondrial rubisco operon into plastids of rhodophytic and chromophytic algae), neither this hypothesis nor the alternative hypothesis of ancient gene duplication have been examined in detail. We have conducted phylogenetic analyses of all available bacterial rbcL sequences, and representative plastid sequences, in order to explore these alternative hypothesis and fully examine the complexity of rubisco gene evolution. The rbcL phylogeny reveals a surprising number of gene relationships that are fundamentally incongruent with organismal relationships as inferred from multiple lines of other molecular evidence. On the order of six horizontal gene transfers are implied by the form I (L8S8) rbcL phylogeny, two between cyanobacteria and proteobacteria, one between proteobacteria and plastids, and three within proteobacteria. Alternatively, a single ancient duplication of the form I rubisco operon, followed by repeated and pervasive differential loss of one operon or the other, would account for much of this incongruity. In all probability, the rubisco operon has undergone multiple events of both horizontal gene transfer and gene duplication in different lineages.

Bacteria↗

Splicing profile based protein categorization between human and mouse genomes by use of the DDBJ Web services.

In one scenario of gene evolution, exon shuffling plays a fundamental role in increasing gene diversity. This paper is an appraisal of the biological relevance of categorising proteins by their splicing profiles (exon-intron structures). The central question is whether protein function is more correlated with splicing profiles than sequence similarity, or not. To approach this question, a splicing profile similarity (SPS) index, which measures relative exon length discrepancy, was devised. Arbitrary human proteins were compared, in terms of SPS and amino acid sequence similarity, to their 1) mouse orthologues and 2) human paralogues, which epitomise functional equivalence and non-equivalence, respectively, to methodically elucidate the global relationship between a) biological function, b) splicing profile similarity, and c) sequence similarity. Protein function is more correlated with splicing profile similarity than sequence similarity as demonstrated by the fact that human-mouse orthologues (HMOs) display significantly higher splicing profile similarity than do human-human paralogues (HHPs), despite the mutual sequence similarity between these two categories. This finding indicates that splicing profile-based protein categorisation is biologically meaningful.

Alternative Splicing↗

The sequence of the gorilla fetal globin genes: evidence for multiple gene conversions in human evolution.

Two fetal globin genes (G gamma and A gamma) from one chromosome of a lowland gorilla (Gorilla gorilla gorilla) have been sequenced and compared to three human loci (a G gamma-gene and two A gamma-alleles). A comparison of regions of local homology among these five sequences indicates that long after the duplication that produced the two nonallelic gamma-globin loci of catarrhine primates, about 35 million years (Myr) ago, at least one gene conversion event occurred between these loci. This conversion occurred not long before the ancestral divergence (about 6 Myr ago) of Homo and Gorilla. After this ancestral divergence, a minimum of three more gene conversion events occurred in the human lineage. Each human A gamma-allele shares specific sequence features with the gorilla A gamma-gene; one such distinctive allelic feature involves the simple repeated sequence in IVS 2. This suggests that early in the human lineage the A gamma-genes may have undergone a crossing-over event mediated by this simple repeated sequence. The DNA sequences from coding regions of both G gamma- and A gamma-loci, a comparison of 292 codons in the corresponding gorilla and human genes, show an unusually low evolutionary rate, with only two nonsilent differences and, surprisingly, not even one silent substitution. The two nonsynonymous substitutions observed predict a glycine at codon 73 and an arginine at codon 104 in the gorilla A gamma-sequence rather than aspartic acid and lysine, respectively, in human A gamma. Because only arginine has been found at position 104 in gamma-chains of Old World monkeys, it may represent the ancestral residue lost in gorilla and human G gamma-chains and in the human A gamma-chain. Possibly the arginine codon (AGG) was replaced by the lysine codon (AAG) in the G gamma-gene of a common ancestor of Homo and Gorilla and then was transferred to the A gamma-gene by subsequent conversions in the human lineage. DNA sequence conversions, similar to that attributed to the fetal gamma-globin genes, appear to be relatively frequent phenomena and, if widespread throughout the genome, may have profound evolutionary consequences.

Alleles↗

Plant LTR-retrotransposons and MITEs: control of transposition and impact on the evolution of plant genes and genomes.

Transposons are genetic elements that can move, and sometimes spread, within genomes, and that constitute an important fraction of eukaryote genomes. Two types of transposons, long terminal repeat (LTR)-retrotransposons and miniature inverted-repeat transposable elements (MITEs), are highly represented in plant genomes, and can account for as much as 50-80% of the total DNA content. In the last few years it has been shown that, in spite of their mutagenic capacity, both LTR-retrotransposons and MITEs can be found associated to genes, suggesting that their activity has influenced the evolution of plant genes. In this review we will summarise recent data on the control of the activity and the impact of both LTR-retrotransposons and MITEs on the evolution of plant genes and genomes.

DNA Transposable Elements↗