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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↗

Alternative splicing, the gene concept, and evolution.

Alternative splicing allows for the production of many gene products from a single coding sequence. I introduce the concept of alternative splicing via some examples. I then discuss some current hypotheses about the explanatory role of alternative splicing, including the claim that splicing is a significant contributor to the difference in complexity between the human genome and proteosome. Hypotheses such as these bring into question our working concepts of the gene. I examine several gene concepts introduced to cope with processes such as alternative splicing. Next I introduce some hypotheses about the evolution of mechanisms alternative splicing in higher organisms. I conclude that attention to alternative splicing reveals that we adopt an attitude that developmental theorizing must inform evolutionary theorizing and vice versa.

Alternative Splicing↗

Expansion of the Hox gene family and the evolution of chordates.

Homeobox genes encode DNA-binding transcription regulators that participate in the formation of embryonic pattern or contribute to cell-type specificity during metazoan development. Homeobox genes that regulate axial patterning and segmental identity (Hox/HOM genes) share a conserved clustered genomic organization. Mammals have four clusters that have likely arisen from the duplication of a single ancestral cluster. The number of Hox-type genes in other deuterostomes was estimated by using a polymerase chain reaction sampling method. Increased Hox gene complements are associated with the appearance of chordate and vertebrate characters. Our data suggest the presence of one Hox cluster in the acorn worm, a hemichordate; two Hox clusters in amphioxus, a cephalochordate; and three in the lamprey, a primitive vertebrate.

Animals↗

Divergent evolution of fucosyltransferase genes from vertebrates, invertebrates, and bacteria.

On the basis of function and sequence similarities, the vertebrate fucosyltransferases can be classified into three groups: alpha-2-, alpha-3-, and alpha-6-fucosyltransferases. Thirty new putative fucosyltransferase genes from invertebrates and bacteria and six conserved peptide motifs have been identified in DNA and protein databanks. Two of these motifs are specific of alpha-3-fucosyltransferases, one is specific of alpha-2-fucosyltransferases, another is specific of alpha-6-fucosyltransferases, and two are shared by both alpha-2- and alpha-6-fucosyltranserases. Based on these data, literature data, and the phylogenetic analysis of the conserved peptide motifs, a model for the evolution offucosyltransferase genes by successive duplications, followed by divergent evolution is proposed, with either two different ancestors, one for the alpha-2/6-fucosyltransferases and one for the alpha-3-fucosyltransferases or a single common ancestor for the two families. The expected properties of such an hypothetical ancestor suggest that the plant or insect alpha-3-fucosyltransferases using chitobiose as acceptor might be the present forms of this ancestor, since fucosyltransferases using chitobiose as acceptor are expected to be of earlier appearance in evolution than enzymes using N -acetyllactosamine. However, an example of convergent evolution of fucosyltransferase genes is suggested for the appearance of the Leaepitopes found in plants and primates.

Amino Acid Sequence↗

Evolution of an avirulence gene, AVR1-CO39, concomitant with the evolution and differentiation of Magnaporthe oryzae.

The significance of AVR1-CO39, an avirulence gene of the blast fungus corresponding to Pi-CO39(t) in rice cultivars, during the evolution and differentiation of the blast fungus was evaluated by studying its function and distribution in Pyricularia spp. When the presence or absence of AVR1-CO39 was plotted on a dendrogram constructed from ribosomal DNA sequences, a perfect parallelism was observed between its distribution and the phylogeny of Pyricularia isolates. AVR1-CO39 homologs were exclusively present in one species, Pyricularia oryzae, suggesting that AVR1-CO39 appeared during the early stage of evolution of P. oryzae. Transformation assays showed that all the cloned homologs tested are functional as an avirulence gene, indicating that selection has maintained their function. Nevertheless, Oryza isolates (isolates virulent on Oryza spp.) in P. oryzae were exceptionally noncarriers of AVR1-CO39. All Oryza isolates suffered from one of the two types of known rearrangements at the Avr1-CO39 locus (i.e., G type and J type). These types were congruous to the two major lineages of Oryza isolates from Japan determined by MGR586 and MAGGY. These results indicate that AVR1-CO39 was lost during the early stage of evolution of the Oryza-specific subgroup of P. oryzae. Interestingly, its corresponding resistance gene, Pi-CO39(t), is not widely distributed in Oryza spp.

Evolution, Molecular↗

Development gene networks and evolution.

Animal development relies on complex programs of gene regulation that are likely to account for a significant fraction of the information carried in genomes. The evolution of these regulatory programs is a major contributor to the diversity of animal forms, yet the architecture of the transcriptional networks that comprise developmental programs is only beginning to come into focus. The sea urchin offers an uncomplicated system in which to study transcriptional regulation and the networks that direct embryogenesis. This review describes the approaches that we are taking towards this problem using the sea urchin embryo and some comparative methods that will eventually lead to a deeper understanding of the evolution of developmental networks.

Animals↗

Five Nkx5 genes show differential expression patterns in anlagen of sensory organs in medaka: insight into the evolution of the gene family.

We report the identification and characterisation of five different Nkx5-related genes in medaka fish (Oryzias latipes). They constitute homologues of genes previously isolated in higher vertebrates, Nkx5--1, Nkx5--2, Hmx1/Nkx5--3 and SOHo-1, and were named accordingly: OlNkx5--1.1, OlNkx5--2, OlNkx5--3 and OlSOHo. For the Nkx5--1 gene a new, second homologue, OlNkx5--1.2, was isolated. In medaka, Nkx5 and SOHo genes are differentially expressed in three developing sensory organs: eye, ear and lateral line and later in defined brain regions. Phylogenetic analyses of the entire Nkx5 family revealed that four paralogous Nkx5 groups, Nkx5--1, Nkx5--2, Hmx1/Nkx5--3/GH6 and SOHo, are present in vertebrates. Only some of the Nkx5 family members have been identified in singular vertebrate species so far. Here we present, for the first time, the isolation of representatives of each Nkx5 subgroup in one species, the medaka fish. Based on similarities in sequence and expression patterns, and genomic organisation we propose a model of the evolutionary history of the Nkx5 family. The model predicts that the four vertebrate Nkx5 genes arose by a tandem duplication, followed by chromosomal duplication. The two Nkx5--1 genes identified so far exclusively in medaka most probably result from an additional genome duplication in the fish lineage.

Amino Acid Sequence↗

Bacteria are different: observations, interpretations, speculations, and opinions about the mechanisms of adaptive evolution in prokaryotes.

To some extent, the genetic theory of adaptive evolution in bacteria is a simple extension of that developed for sexually reproducing eukaryotes. In other, fundamental ways, the process of adaptive evolution in bacteria is quantitatively and qualitatively different from that of organisms for which recombination is an integral part of the reproduction process. In this speculative and opinionated discussion, we explore these differences. In particular, we consider (i) how, as a consequence of the low rates of recombination, "ordinary" chromosomal gene evolution in bacteria is different from that in organisms where recombination is frequent and (ii) the fundamental role of the horizontal transmission of genes and accessory genetic elements as sources of variation in bacteria. We conclude with speculations about the evolution of accessory elements and their role in the adaptive evolution of bacteria.

Bacteria↗

Identification and simulation of shifted periodicities common to protein coding genes of eukaryotes, prokaryotes and viruses.

The distribution of nucleotides in protein coding genes is studied with autocorrelation functions. The autocorrelation function YRY(N)iYRY, analysing the occurrence probability of the i-motif YRY(N)iYRY (two motifs YRY separated by any i bases N, R = purine = Adenine or Guanine, Y = pyrimidine = Cytosine or Thymine, N = R or Y) in the protein coding genes of eukaryotes, prokaryotes and viruses, reveals the classical periodicity 0 modulo 3 associated with the normal frame 0 (maximal values of the function at i = 0, 3, 6, etc). The specification of YRY(N)iYRY on the alphabet [A, C, G, T] leads to 64 i-motifs: CAC(N)iCAC, CAC(N)iCAT, ..., TGF(N)iTGT. The 64 autocorrelation functions associated with these 64 i-motifs in protein coding genes have all the periodicity modulo 3, but, surprisingly, not always the expected periodicity 0 modulo 3. Two new types of periodicities are identified: a periodicity 1 modulo 3 associated with the shifted frame +1 (maximal values of the function at i = 1, 4, 7, etc) and a periodicity 2 modulo 3 associated with the shifted frame -1 (maximal values of the function at i = 2, 5, 8 etc). Furthermore, the classification of i-motifs according to the type of periodicity demonstrates a strong coherence relation between the 64 i-motifs, which is, in addition, common to the three gene populations, as the same i-motifs in the three gene populations have the same periodicities. The three periodicities 0, 1 and 2 modulo 3 can be simulated by an evolutionary model at two successive processes. The simulated genes are generated by a process of gene construction, with a stochastic automaton followed by a process of gene evolution with random insertions and deletions of trinucleotides simulating RNA editing. For almost all i-motifs, the autocorrelation functions in these simulated genes are strongly correlated with those in protein coding genes, for both the type and the probability level of periodicities. This paper describes the process of ribosomal frameshifting leading to the shifted periodicities, which may reveal overlapping genes or concatenated genes from different frames. It also presents the evolutionary aspects of the shifted periodicities. The shifted periodicities cannot be associated with the RNY model (Eigen & Schuster, 1978, Naturwissenschaften 65, 341-369) or the RRY model (Crick et al., 1976, Origins of Life 7, 389-397), but are compatible with the oligonucleotide mixing model (Arquès & Michel, 1990, Bull. math. Biol. 52, 741-772). Finally, a variant of the primitive translation model of Crick et al. (1976) is proposed to explain the shifted periodicities.

Animals↗

Origin and evolution of overlapping genes in the family Microviridae.

The possibility of creating novel genes from pre-existing sequences, known as overprinting, is a widespread phenomenon in small viruses. Here, the origin and evolution of gene overlap in the bacteriophages belonging to the family Microviridae have been investigated. The distinction between ancestral and derived frames was carried out by comparing the patterns of codon usage in overlapping and non-overlapping genes. By this approach, a gradual increase in complexity of the phage genome--from an ancestral state lacking gene overlap to a derived state with a high density of genetic information--was inferred. Genes encoding less-essential proteins, yet playing a role in phage growth and diffusion, were predicted to be novel genes that originated by overprinting. Evaluation of the rates of synonymous and non-synonymous substitution yielded evidence for overlapping genes under positive selection in one frame and purifying selection in the alternative frame.

Coliphages↗

Biochemical networking contributes more to genetic buffering in human and mouse metabolic pathways than does gene duplication.

During evolution different genes evolve at unequal rates, reflecting the varying functional constraints on phenotype. An important contributor to this variation is genetic buffering, which reduces the potential detrimental effects of mutations. We studied whether gene duplication and redundant metabolic networks affect genetic buffering by comparing the evolutionary rate of 242 human and mouse orthologous genes involved in metabolic pathways. A gene with a redundant network is defined as one for which the structural layout of metabolic pathways provides an alternative metabolic route that can, in principle, compensate for the loss of a protein function encoded by the gene. We found that genes with redundant networks evolve at similar rates as did genes without redundant networks, [corrected] but no significant difference was detected between single-copy genes and gene families. This implies that redundancy in metabolic networks provides significantly more genetic buffering than do gene families. We also found that genes encoding proteins involved in glycolysis and gluconeogenesis showed as a group a distinct pattern of variation, in contrast to genes involved in other pathways. These results suggest that redundant networks provide genetic buffering and contribute to the functional diversification of metabolic pathways.

Animals↗

Genomic evolution of Hox gene clusters.

The family of Hox genes, which number 4 to 48 per genome depending on the animal, control morphologies on the main body axis of nearly all metazoans. The conventional wisdom is that Hox genes are arranged in chromosomal clusters in colinear order with their expression patterns on the body axis. However, recent evidence has shown that Hox gene clusters are fragmented, reduced, or expanded in many animals-findings that correlate with interesting morphological changes in evolution. Hox gene clusters also contain many noncoding RNAs, such as intergenic regulatory transcripts and evolutionarily conserved microRNAs, some of whose developmental functions have recently been explored.

Animals↗

Homeobox genes in vertebrate evolution.

A wide range of anatomical features are shared by all vertebrates, but absent in our closest invertebrate relatives. The origin of vertebrate embryogenesis must have involved the evolution of new regulatory pathways to control the development of new features, but how did this occur? Mutations affecting regulatory genes, including those containing homeobox sequences, may have been important: for example, perhaps gene duplications allowed recruitment of genes to new roles. Here I ask whether comparative data on the genomic organization and expression patterns of homeobox genes support this hypothesis. I propose a model in which duplications of particular homeobox genes, followed by the acquisition of gene-specific secondary expression domains, allowed the evolution of the neural crest, extensive organogenesis and craniofacial morphogenesis. Specific details of the model are amenable to testing by extension of this comparative approach to molecular embryology.

Animals↗

Variation in V lambda genes in the genus Mus.

The complement of Ig V lambda genes in nine species of feral mice representing the four extant subgenera of the genus Mus was examined and compared with that of BALB/c inbred mice. Although all inbred strains examined have two V lambda genes, there is variation in the number of copies of V lambda genes in the wild mice. All feral representatives of M. musculus domesticus, from which inbred strains are derived, have at least three V lambda genes, indicating that a V lambda gene may have been lost during the inbreeding process. At least three V lambda genes are also found in representatives of three other M. musculus subspecies, including the stock of M. musculus musculus "Czech II" shown to have at least 12 C lambda genes. In comparing the complement of V lambda and C lambda genes in these animals, evidence is found that supports a mechanism of lambda gene reiteration involving duplication of a unit containing a V lambda and two C lambda genes. However, the possibility that C lambda gene amplification occurred independent of V lambda gene evolution cannot be ruled out. M. spicelegus and M. spretus, species that are semifertile with M. musculus, have one to three V lambda genes. Species more distantly related to M. musculus, such as M. cookii and M. platythrix, appear to have more (four to six) V lambda genes. Greater V lambda gene heterogeneity is also found in these animals. We propose that the ancestors of the subgenus Mus had more V lambda genes than are seen in modern species and that the paucity of V lambda genes in M. musculus, M. spicelegus, and M. spretus may be the result of V lambda gene deletion events that occurred since the divergence of the ancestor of these three species and those of the distantly related species.

Animals↗

Protein interactions limit the rate of evolution of photosynthetic genes in cyanobacteria.

Using a bioinformatic approach, we analyzed the correspondence in genetic distance matrices between all possible pairwise combinations of 82 photosynthetic genes in 10 species of cyanobacteria. Our analysis reveals significant correlations between proteins linked in a conserved gene order and between structurally identified interacting protein scaffolds that coordinate the binding of cofactors involved in photosynthetic electron transport. Analyses of amino acid substitution rates suggest that the tempo of evolution of genes encoding core metabolic processes in the photosynthetic apparatus is highly constrained by protein-protein, protein-lipid, and protein-cofactor interactions (collectively called "protein interactions"). These interactions are critical for energy transduction, primary charge separation, and electron transport and effectively act as an internal selection pressure governing the conservation of clusters of photosynthetic genes in oxygenic prokaryotic photoautotrophs. Consequently, although several proteins within the photosynthetic apparatus are biophysically and physiologically inefficient, selection has not significantly altered the genes encoding these essential proteins over billions of years of evolution. In effect, these core proteins have become "frozen metabolic accidents."

Computational Biology↗

The structural organisation of the gene encoding class II starch synthase of wheat and barley and the evolution of the genes encoding starch synthases in plants.

Wheat and barley contain at least four classes of starch synthases in the endosperm, granule bound starch synthase I (GBSSI) and starch synthases I, II and III (SSI, SSII, SSIII). In this work, SSII in barley is shown to be associated with the starch granule by using antibodies. A cDNA from barley encoding SSII and the genes for SSII from barley and Aegilops tauschii ( A. tauschii, the D genome donor to wheat) are characterised. Fluorescent in situ hybridisation (FISH) and PCR were used to localise the wheat SSII gene to the short arm of chromosome 7, showing synteny with the location of the rice SSII gene to the short arm of chromosome 6. Comparison of the genes encoding SSII of A. tauschii, barley and Arabidopsis showed a conserved exon-intron structure although the size of the introns varied considerably. Extending such comparison between the genes encoding starch synthases (GBSSI, SSI, SSII and SSIII) from A. tauschii and Arabidopsis showed that the exon-intron structures are essentially conserved. Separate and distinct genes for the individual starch synthases therefore existed before the separation of monocotyledons and dicotyledons.

Base Sequence↗

Only one nemo-like kinase gene homologue in invertebrate and mammalian genomes.

The nemo-like kinase (Nlk) connects the MAP kinase and Wnt signalling pathways. We have found that invertebrate (Caenorhabditis elegans, Drosophila melanogaster) and mammalian genomes (Mus musculus and Homo sapiens) each contain only a single functional Nlk gene. The mouse genome also harbours a transcriptionally silent processed Nlk pseudogene residing on chromosome 2. Thus, while genes encoding upstream (such as Wnts and frizzelds) and downstream (such as TCF/LEF) components of the Wnt signalling pathway have been extensively diversified during evolution, genes encoding components of the common core of the connecting signalling structure (such as beta-catenin, GSK beta and Nlk) have been maintained in single copies.

Amino Acid Sequence↗