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PubMedDate not supplied

Evolving beyond perfection: an investigation of the effects of long-term evolution on fractal gene regulatory networks.

This paper continues a theme of exploring algorithms based on principles of biological development for tasks such as pattern generation, machine learning and robot control. Previous work has investigated the use of genes expressed as fractal proteins to enable greater evolvability of gene regulatory networks (GRNs). Here, the evolution of such GRNs is investigated further to determine whether evolution exhibits natural tendencies towards efficiency and graceful degradation of developmental programs. Experiments where "perfect" GRNs are evolved for a further thousand generations without the addition of any further selection pressure, confirm this hypothesis. After further evolution, the perfect GRNs operate in a more efficient manner (using fewer proteins) and show an improved ability to function correctly with missing genes. When the algorithm is applied to applications (e.g. robot control) this equates to efficient and fault-tolerant controllers.

Algorithms↗

PubMed1984

Duplication of a four-gene set during the evolution of the goat beta-globin locus produced genes now expressed differentially in development.

Genomic clones which link the goat preadult (beta C) and adult (beta A) beta-globin genes have been isolated. These overlapping clones contain a previously unidentified embryonic like globin gene (epsilon III) and establish the following linkage map of eight genes in the goat beta-globin locus: epsilon I-epsilon II-psi beta X-beta C-epsilon III-epsilon IV-psi beta Z-beta A. This linkage map and the nucleotide sequence of the eight genes document a relatively recent duplication of a four-gene set: epsilon-epsilon-psi beta-beta. This duplication produced two genes (beta C and beta A) which are now expressed differentially during development. An embryonic like globin gene located downstream from beta A has also been isolated. The embryonic nature of this gene as well as the adult beta-like sequence of the goat fetal globin gene (gamma) suggest that a duplication of the four-gene set also produced the globin gene now expressed during fetal development.

Aging↗

PubMed1999

Structure and expression of tandemly duplicated xanthine dehydrogenase genes of the silkworm (Bombyx mori).

Xanthine dehydrogenase (XDH) is a molybdoenzyme which catalyses oxidation of xanthine and hypoxanthine to uric acid. We isolated genomic clones of silkworm (Bombyx mori) XDH genes (BmXDH1 and BmXDH2). The BmXDH2 gene is located upstream from the BmXDH1 gene and they show a tandemly duplicated structure. Both BmXDH genes were expressed in the fat body and Malpighian tubules, whereas only the BmXDH1 gene was expressed in the midgut. Phylogenetic analysis indicates that BmXDH gene duplication occurred after the divergence of the silkworm and dipteran species. Intron insertion site comparison shows that some introns were lost during insect XDH gene evolution.

Amino Acid Sequence↗

PubMed1999

The Venus flytrap of periplasmic binding proteins: an ancient protein module present in multiple drug receptors.

Located between the inner and outer membranes of Gram-negative bacteria, periplasmic binding proteins (PBPs) scavenge or sense diverse nutrients in the environment by coupling to transporters or chemotaxis receptors in the inner membrane. Their three-dimensional structures have been deduced in atomic detail with the use of X-ray crystallography, both in the free and liganded state. PBPs consist of two large lobes that close around the bound ligand, resembling a Venus flytrap. This architecture is reiterated in transcriptional regulators, such as the lac repressors. In the process of evolution, genes encoding the PBPs have fused with genes for integral membrane proteins. Thus, diverse mammalian receptors contain extracellular ligand binding domains that are homologous to the PBPs; these include glutamate/glycine-gated ion channels such as the NMDA receptor, G protein-coupled receptors, including metabotropic glutamate, GABA-B, calcium sensing, and pheromone receptors, and atrial natriuretic peptide-guanylate cyclase receptors. Many of these receptors are promising drug targets. On the basis of homology to PBPs and a recently resolved crystal structure of the extracellular binding domain of a glutamate receptor ion channel, it is possible to construct three-dimensional models of their ligand binding domains. Together with the extensive information available on the mechanism of ligand binding to PBPs, such models can serve as a guide in drug discovery.

Animals↗

PubMed2006

Variation in synonymous codon use and DNA polymorphism within the Drosophila genome.

A strong negative correlation between the rate of amino-acid substitution and codon usage bias in Drosophila has been attributed to interference between positive selection at nonsynonymous sites and weak selection on codon usage. To further explore this possibility we have investigated polymorphism and divergence at three kinds of sites: synonymous, nonsynonymous and intronic in relation to codon bias in D. melanogaster and D. simulans. We confirmed that protein evolution is one of the main explicative parameters for interlocus codon bias variation (r(2) approximately 40%). However, intron or synonymous diversities, which could have been expected to be good indicators of local interference [here defined as the additional increase of drift due to selection on tightly linked sites, also called 'genetic draft' by Gillespie (2000)] did not covary significantly with codon bias or with protein evolution. Concurrently, levels of polymorphism were reduced in regions of low recombination rates whereas codon bias was not. Finally, while nonsynonymous diversities were very well correlated between species, neither synonymous nor intron diversities observed in D. melanogaster were correlated with those observed in D. simulans. All together, our results suggest that the selective constraint on the protein is a stable component of gene evolution while local interference is not. The pattern of variation in genetic draft along the genome therefore seems to be instable through evolutionary times and should therefore be considered as a minor determinant of codon bias variance. We argue that selective constraints for optimal codon usage are likely to be correlated with selective constraints on the protein, both between codons within a gene, as previously suggested, and also between genes within a genome.

Animals↗

PubMed2006

Molecular evolution of plant immune system genes.

Molecular population genetic studies are providing new perspectives on the evolution of genes that confer resistance to pathogens and herbivores. Here, we compare the evolutionary history of different components of the defense response (detection, signaling and response) and of genes with parallel function in plants and Drosophila. A review of the literature indicates that the dominant form of selection acting on defense genes (balancing, positive and purifying) differs among components of defense. Sampling of particular classes of genes and genes from non-model organisms, however, remains limited. Future studies combining molecular evolutionary analyses with ecological genetic and functional analyses should better reveal how natural selection has shaped defense gene evolution.

Animals↗

PubMed1994

Intronic gene conversion in the evolution of human X-linked color vision genes.

Human red and green visual pigment genes are X-linked duplicate genes. To study their evolutionary history, introns 2 and 4 (1,987 and 1,552 bp, respectively) of human red and green pigment genes were sequenced. Surprisingly, we found that intron 4 sequences of these two genes are identical and that the intron 2 sequences differ by only 0.3%. The low divergences are unexpected because the duplication event producing the two genes is believed to have occurred before the separation of the human and Old World monkey (OWM) lineages. Indeed, the divergences in the two introns are significantly lower than both the synonymous divergence (3.2% +/- 1.1%) and the nonsynonymous divergence (2.0% +/- 0.5%) in the coding sequences (exons 1-6). A comparison of partial sequences of exons 4 and 5 of human and OWM red and green pigment genes supports the hypothesis that the gene duplication occurred before the human-OWM split. In conclusion, the high similarities in the two intron sequences might be due to very recent gene conversion, probably during evolution of the human lineage.

Animals↗

PubMed2005

Comparison of the oxidative phosphorylation (OXPHOS) nuclear genes in the genomes of Drosophila melanogaster, Drosophila pseudoobscura and Anopheles gambiae.

BACKGROUND: In eukaryotic cells, oxidative phosphorylation (OXPHOS) uses the products of both nuclear and mitochondrial genes to generate cellular ATP. Interspecies comparative analysis of these genes, which appear to be under strong functional constraints, may shed light on the evolutionary mechanisms that act on a set of genes correlated by function and subcellular localization of their products. RESULTS: We have identified and annotated the Drosophila melanogaster, D. pseudoobscura and Anopheles gambiae orthologs of 78 nuclear genes encoding mitochondrial proteins involved in oxidative phosphorylation by a comparative analysis of their genomic sequences and organization. We have also identified 47 genes in these three dipteran species each of which shares significant sequence homology with one of the above-mentioned OXPHOS orthologs, and which are likely to have originated by duplication during evolution. Gene structure and intron length are essentially conserved in the three species, although gain or loss of introns is common in A. gambiae. In most tissues of D. melanogaster and A. gambiae the expression level of the duplicate gene is much lower than that of the original gene, and in D. melanogaster at least, its expression is almost always strongly testis-biased, in contrast to the soma-biased expression of the parent gene. CONCLUSIONS: Quickly achieving an expression pattern different from the parent genes may be required for new OXPHOS gene duplicates to be maintained in the genome. This may be a general evolutionary mechanism for originating phenotypic changes that could lead to species differentiation.

Animals↗

PubMed1995

p53 gene mutations inside and outside of exons 5-8: the patterns differ in breast and other cancers.

Most studies of mutations in the p53 tumor suppressor gene in tumors have examined only exons 5-8. Our laboratory previously found 64 mutations in exons 5-8 of the p53 gene in 194 primary breast cancers. Herein, we report 18 additional mutations found outside of exons 5-8. Mutations are present in exons 4, 9 and 10, and flanking splice junctions, but not in the promotor region or in exons 1, 2, 3 and 11. No missense mutations are found outside of exons 5-8. Instead, there is a predominance of frameshift mutations with lesser numbers of nonsense and splice site mutations. In contrast, the majority of mutations in exons 5-8 in this sample are missense changes and all of these are at amino acids that are identical in the 11 known p53 sequences that represent about 1.6 billion years of evolutionary divergence. The difference in mutational pattern between these two regions of the p53 gene is due to a lack of missense mutations and inframe microdeletions outside of exons 5-8. A review of our database of p53 mutations (De Vries et al., in preparation) shows that the patterns of mutation inside and outside of exons 5-8 differ in other types of cancers as well. The paucity of missense mutations in exons 2-4 and 9-11 in breast and other cancers (even at amino acids identical throughout p53 gene evolution) suggest that at least some missense mutations result in a phenotype other than malignant transformation. These data also illustrate the importance of examining identical exons when comparing the pattern of p53 gene mutations in different populations.

Adult↗

PubMed2006

Modeling amino acid substitution patterns in orthologous and paralogous genes.

We study to what degree patterns of amino acid substitution vary between genes using two models of protein-coding gene evolution. The first divides the amino acids into groups, with one substitution rate for pairs of residues in the same group and a second for those in differing groups. Unlike previous applications of this model, the groups themselves are estimated from data by simulated annealing. The second model makes substitution rates a function of the physical and chemical similarity between two residues. Because we model the evolution of coding DNA sequences as opposed to protein sequences, artifacts arising from the differing numbers of nucleotide substitutions required to bring about various amino acid substitutions are avoided. Using 10 alignments of related sequences (five of orthologous genes and five gene families), we do find differences in substitution patterns. We also find that, although patterns of amino acid substitution vary temporally within the history of a gene, variation is not greater in paralogous than in orthologous genes. Improved understanding of such gene-specific variation in substitution patterns may have implications for applications such as sequence alignment and phylogenetic inference.

Actins↗

PubMed1990

Structure and sequence determination of the gene encoding human salivary statherin.

Human statherin (STT) is a low-Mr (43 amino acids) acidic phosphoprotein secreted mainly by salivary glands. It acts as an inhibitor of precipitation of Ca.phosphate salts in the oral cavity. DNA (12.2 kb) was isolated from human genomic phage lambda libraries as a series of overlapping clones, and the nucleotide sequence of the STT-encoding gene (STT) was determined. The transcribed region spans 6.5 kb and contains six exons and five introns. Upstream DNA (1.6 kb) was also sequenced and a number of possible regulatory elements were identified. The exon-intron boundaries of the STT gene roughly coincide with the protein-coding regions of the mRNA and with the functional domains of STT. This pattern of organization has been seen in a variety of eukaryotic genes and is consistent with the domain theory of gene evolution.

Amino Acid Sequence↗

PubMed2000

External pH: an environmental signal that helps to rationalize pel gene duplication in Erwinia chrysanthemi.

The phytopathogenic bacterium Erwinia chrysanthemi produces five major pectate lyases that are key virulence factors in soft-rot disease development. Using transcriptional fusions, we studied the regulation of pelA, pelD, and pelE gene expression as a function of variation of the external pH. pelA and pelD were expressed when bacteria were grown in an acidic medium while pelE was transcribed only in basic medium. Using phenol red, we observed that, in chicory leaves, pH value of infected tissue varies from acidic to basic. Taken together, these findings are discussed in the context of a model unifying both catalysis and regulation to account for pel gene evolution. In particular, we propose that the three isoenzymes are produced sequentially during the infection process.

Dickeya chrysanthemi↗

PubMed2002

Lateral gene transfer and parallel evolution in the history of glutathione biosynthesis genes.

BACKGROUND: Glutathione is found primarily in eukaryotes and in Gram-negative bacteria. It has been proposed that eukaryotes acquired the genes for glutathione biosynthesis from the alpha-proteobacterial progenitor of mitochondria. To evaluate this, we have used bioinformatics to analyze sequences of the biosynthetic enzymes gamma-glutamylcysteine ligase and glutathione synthetase. RESULTS: Gamma-glutamylcysteine ligase sequences fall into three groups: sequences primarily from gamma-proteobacteria; sequences from non-plant eukaryotes; and sequences primarily from alpha-proteobacteria and plants. Although pairwise sequence identities between groups are insignificant, conserved sequence motifs are found, suggesting that the proteins are distantly related. The data suggest numerous examples of lateral gene transfer, including a transfer from an alpha-proteobacterium to a plant. Glutathione synthetase sequences fall into two distinct groups: bacterial and eukaryotic. Proteins in both groups have a common structural fold, but the sequences are so divergent that it is uncertain whether these proteins are homologous or arose by convergent evolution. CONCLUSIONS: The evolutionary history of the glutathione biosynthesis genes is more complex than anticipated. Our analysis suggests that the two genes in the pathway were acquired independently. The gene for gamma-glutamylcysteine ligase most probably arose in cyanobacteria and was transferred to other bacteria, eukaryotes and at least one archaeon, although other scenarios cannot be ruled out. Because of high divergence in the sequences, the data neither support nor refute the hypothesis that the eukaryotic gene comes from a mitochondrial progenitor. After acquiring gamma-glutamylcysteine ligase, eukaryotes and most bacteria apparently recruited a protein with the ATP-grasp superfamily structural fold to catalyze synthesis of glutathione from gamma-glutamylcysteine and glycine. The eukaryotic glutathione synthetase did not evolve directly from the bacterial glutathione synthetase.

Animals↗

PubMed1999

Allelic diversity at class II DRB1 and DQB loci of the pig MHC (SLA).

The loci encoding the beta chain of the pig major histocompatibility complex (MHC) class II antigens, SLA-DR and -DQ, have been known to exhibit a remarkable degree of allelic polymorphism. Here, to understand the generation of SLA class II polymorphism, 25 SLA-DRB1 and 24 SLA-DQB genes including newly identified 12 SLA-DRB1 and 7 SLA-DQB genes obtained from miniature pigs were analyzed based on the nucleotide and deduced amino acid sequences. Most of the allelic diversity was attributed to the variable sequences which encode a beta1 domain consisting of a beta-pleated sheet followed by an a helix. In the beta1 domain coding region, there were four GC-rich sequences, which have been considered to involve the intra-exon sequence exchange also in other gene evolutions. The first and second GC-rich sequences were alpha-like sequences, which have been shown to be a putative recombination signal, and were stably conserved among SLA-DRB1 and DQB genes. These alpha-like sequences identified in SLA-DRB1 and SLA-DQB were found to encode the first turning point of the beta-pleated sheet and the boundary between the beta-pleated sheet and the alpha helix. Analysis of clustered sequence variation also suggested intra-exon gene conversions in which the alpha-like sequences act as putative breakpoints. In addition to point mutations and selection mechanism, intra-exon gene conversions must be an important mechanism in the generation of allelic polymorphism at the SLA-DRB1 and SLA-DQB.

Alleles↗

PubMed2005

[Gene orders in genomes of alpha-proteobacteria: similarity and evolution].

The gene orders in the genomes of nine alpha-proteobacteria were compared using quantitative indices S (the relative number of common pairs of adjacent genes) and L (the mean difference between intergenic distances). A sample of 200 homologous genes, occurring in all 11 strains, was studied. In all of the genomes examined, 20 conserved, "uninterrupted" regions, including in total 63 out of 200 genes, were found. The rate of evolutionary change in the gene order widely varied in different evolutionary lineages. The highest rate (40 to 60 genome rearrangements per 100 Myr) was characteristic of the intercellular parasite Wolbachia (Rickettsiales). Computer simulation has showed that the S to L ratio observed in the sample testified that the probability of large genome rearrangements was somewhat lower than that of small ones.

Bacteria↗

PubMed1988

The Drosophila melanogaster tropomyosin II gene produces multiple proteins by use of alternative tissue-specific promoters and alternative splicing.

The structure of the Drosophila melanogaster tropomyosin II (TmII) gene has been determined by DNA sequencing of cDNA clones and the genomic DNA coding for the gene. Two overlapping transcriptional units produce at least four different tropomyosin isoforms. A combination of developmentally regulated promoters and alternative splicing produces both muscle and cytoskeletal tropomyosin isoforms. One promoter is a muscle-specific promoter and produces three different tropomyosin isoforms by alternative splicing of the last three 3' exons. The second promoter has the characteristics of a housekeeping promoter and produces a cytoskeletal tropomyosin isoform. Several internal exons along with a final 3' exon are alternatively spliced in the cytoskeletal transcript. The intron-exon boundaries of the TmII gene are identical to the intron-exon boundaries of all vertebrate tropomyosin genes reported, but are very different from the intron-exon boundaries of the D. melanogaster tropomyosin I gene. The TmII gene is the only reported tropomyosin gene that has two promoters and a quadruple alternative splice choice for the final exon. Models for the mechanism of D. melanogaster tropomyosin gene evolution are discussed.

Animals↗

PubMed1993

Sequence of the gtfK gene of Streptococcus salivarius ATCC 25975 and evolution of the gtf genes of oral streptococci.

Many strains of oral streptococci secrete glucosyltransferases (GTFs) that polymerize sucrose into glucans that form an integral part of the plaque matrix on the tooth surface. Recently, we reported the cloning of two closely linked GTF-encoding genes (gtfJ and gtfK) from Streptococcus salivarius ATCC 25975 as well as the sequence of gtfJ, which encodes a primer-dependent GTF that synthesizes an insoluble product (a GTF-I). In this communication we report the sequence of gtfK, which encodes a primer-dependent GTF that synthesizes a soluble product (a GTF-S), as well as the sequence of a small downstream open reading frame of unknown function. The deduced sequence of GtfK was compared with those of seven other streptococcal Gtfs and an unrooted phylogenetic tree constructed. This analysis suggested that Gtfs with similar product specificities do not form phylogenetic clusters and was consistent with currently accepted phylogenetic schemes. The tree was tested by constructing a series of 'sub-trees' from different blocks of the alignment. Evidence was obtained for recombination events involving gtfB and gtfC from S. mutans GS-5, gtfJ and gtfK from S. salivarius, as well as the gtfI genes from S. downei and S. sobrinus. The recombination events between gtfB and gtfC, and between the two gtfI genes, were confirmed by examining divergences at silent sites.

Algorithms↗

PubMed2006

Ancient lateral gene transfer in the evolution of Bdellovibrio bacteriovorus.

The recently sequenced genome of the predatory delta-proteobacterium Bdellovibrio bacteriovorus provides many insights into its metabolism and evolution. Because its genes are reasonably uniform in G+C content, it was suggested that B. bacteriovorus actively resists recombination with foreign DNA and horizontal transfer of DNA from other bacteria. To investigate this further, we carried out a variety of phylogenetic and comparative genomics analyses using data from >200 microbial genomes, including several published delta-proteobacteria. Although there might be little evidence for the extensive recent transfer of genes, we demonstrate that ancient lateral gene acquisition has shaped the B. bacteriovorus genome to a great extent.

Bdellovibrio↗