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At least 235 records · Page 13Linked to original sources

Experimental evolution of gene duplicates in a bacterial plasmid model.

The fate of gene duplicates subjected to diversifying selection was tested experimentally in a bacterial system. The wild-type TEM-1 beta-lactamase gene confers resistance to ampicillin but not to cefotaxime. Point mutations confer cefotaxime resistance, but they compromise ampicillin resistance. Thus, selection for both drug resistances in a bacterium with two copies of beta-lactamase should favor the divergence of one copy to improve cefotaxime resistance while maintaining the other copy to preserve ampicillin resistance. This selection was performed on a bacterium with identical sequences of beta-lactamase on two separate, compatible plasmids. As expected, one plasmid evolved increased cefotaxime resistance when appropriately strong cefotaxime selection was applied. However, the cefotaxime-resistant plasmid maintained sufficient ampicillin resistance to tolerate the concentration of ampicillin used, and the other plasmid was lost. Hosts carrying both the cefotaxime-resistant and wild-type plasmids were then subjected to various higher concentrations of both drugs to find conditions that would ensure the maintenance of both plasmids. In a striking contradiction to our model, no such conditions were found. The fitness cost of carrying both plasmids increased dramatically as antibiotic levels were raised, and either the wild-type plasmid was lost or the cells did not grow. This study highlights the importance of the cost of duplicate genes and the quantitative nature of the tradeoff in the evolution of gene duplication through functional divergence.

Anti-Bacterial Agents↗

The beta-tubulin gene family of pea: primary structures, genomic organization and intron-dependent evolution of genes.

One gene and two cDNAs encoding three different beta-tubulins (TUB1, TUB2, TUB3) of pea have been cloned and sequenced. The derived amino acid sequences show between 92% and 96% identity relative to one another and to most other beta-tubulins of higher plants and green algae. Two notable extremes are the high similarity of 98% between pea TUB3 and maize beta-tubulin 2 and the relatively low similarity (90%) of the hypocotyl-specific beta-tubulin 1 of soybean to the pea sequences. These similarities do not reflect the molecular phylogeny but rather differences in evolutionary rate of beta-tubulins which are differentially regulated during plant development. Genomic Southern blots reveal a beta-tubulin gene family in pea with at least four separate members including two TUB1 genes, one TUB2 gene and one TUB3 gene. This contradicts an earlier report by Raha et al. (Plant Mol Biol 9: 565-571, 1987) suggesting a tandem repeat organization of tubulin genes in pea. The pea TUB1 gene has two introns in identical positions compared to the beta-tubulin genes from Arabidopsis and soybean. In an attempt to reconstruct the universal ancestor of all present-day tubulin genes the intron positions in 38 different alpha- and beta-tubulin genes from plants, animals, fungi and protozoa were compared. This comparison shows that the primordial gene probably had many introns (more than 20) separating 'protoexons' of 15 to 20 codons in agreement with the 'exon theory of genes'. It also supports the view that, during the course of evolution, introns have shifted and were deleted preferentially in the 3' part of the genes. Similar observations have been made previously for other genes. They can be interpreted in terms of a homologous recombination of genes with their modified (incorrectly spliced) and reverse-transcribed pre-mRNAs.

Amino Acid Sequence↗

Gain of function mutations for paralogous Hox genes: implications for the evolution of Hox gene function.

To investigate the functions of paralogous Hox genes, we compared the phenotypic consequences of altering the embryonic patterns of expression of Hoxb-8 and Hoxc-8 in transgenic mice. A comparison of the phenotypic consequences of altered expression of the two paralogs in the axial skeletons of newborns revealed an array of common transformations as well as morphological changes unique to each gene. Divergence of function of the two paralogs was clearly evident in costal derivatives, where increased expression of the two genes affected opposite ends of the ribs. Many of the morphological consequences of expanding the mesodermal domain and magnitude of expression of either gene were atavistic, inducing the transformation of axial skeletal structures from a modern to an earlier evolutionary form. We propose that regional specialization of the vertebral column has been driven by regionalization of Hox gene function and that a major aspect of this evolutionary progression may have been restriction of Hox gene expression.

Animals↗

Isolation and characterization of human blood-coagulation factor X cDNA.

Using synthetic oligodeoxynucleotides as probes, we have isolated factor X cDNA from human liver cDNA library. We sequenced the 1430-bp cDNA which spans the coding region of the mature factor X and contains the polyadenylation signal and poly(A) tail. The amino acid (aa) sequence is in agreement with the published aa sequence. The nucleotide (nt) sequence of cDNA confirmed that factor X is synthesized and secreted as a single-chain precursor, and then converted into dimeric form by proteolytic cleavage of an internal tripeptide. From the nt sequence, it was also predicted that like other secretory proteins, human factor X is synthesized with a leader sequence (prepro-protein). The 5'-coding region of factor X cDNA is 60 and 40% homologous to the corresponding regions of factor IX and prothrombin genes, respectively. This supports the hypothesis of gene evolution by gene duplication followed by divergence.

Amino Acid Sequence↗

Evolution of protein structural classes and protein sequence families.

In protein structure space, protein structures cluster into four elongated regions when mapped based solely on similarity among the 3D structures. These four regions correspond to the four major classes of present-day proteins defined by the contents of secondary structure types and their topological arrangement. Evolution of and restriction to these four classes suggest that, in most cases, the evolution of genes may have been constrained or selected to those genetic changes that results in structurally stable proteins occupying one of the four "allowed" regions of the protein structure space, "structural selection," an important component of natural selection in gene evolution. Our studies on tracing the "common structural ancestor" for each protein sequence family of known structure suggest that: (i) recently emerged proteins belong mostly to three classes; (ii) the proteins that emerged earlier evolved to gain a new class; and (iii) the proteins that emerged earliest evolved to become the present-day proteins in the four major classes, with the fourth-class proteins becoming the most dominant population. Furthermore, our studies also show that not all present-day proteins evolved from one single set of proteins in the last common ancestral organism, but new common ancestral proteins were "born" at different evolutionary times, not traceable to one or two ancestral proteins: "the multiple birth model" for the evolution of protein sequence families.

Evolution, Molecular↗

Minisatellite instability at the Adh locus reveals somatic polymorphism in amphioxus.

Amphioxus (subphylum Cephalochordata) is the closest living relative to vertebrates and widely used for phylogenetic analyses of vertebrate gene evolution. Amphioxus genes are highly polymorphic, but the origin and nature of this variability is unknown. We have analyzed the alcohol dehydrogenase locus (Adh3) in two amphioxus species (Branchiostoma lanceolatum and Branchiostoma floridae) and found that genetic variation is related to repetitive DNA sequences, mainly minisatellites. Small pool-PCR assays indicated that allelic variants are generated by minisatellite instability. We conclude that the generation of new forms was not preferentially linked to germline processes but rather to somatic events leading to mosaic adult animals. Furthermore, most Adh minisatellites belong to a novel class, which we have named mirages. Their distinctive feature is that the repeat subunit spans the exon-intron boundaries and generates potential duplications of the splice sites. However, splicing may not be compromised as no aberrant mRNA variants were detected.

Alcohol Dehydrogenase↗

Genes lost and genes found: evolution of bacterial pathogenesis and symbiosis.

Traditionally, evolutionary biologists have viewed mutations within individual genes as the major source of phenotypic variation leading to adaptation through natural selection, and ultimately generating diversity among species. Although such processes must contribute to the initial development of gene functions and their subsequent fine-tuning, changes in genome repertoire, occurring through gene acquisition and deletion, are the major events underlying the emergence and evolution of bacterial pathogens and symbionts. Furthermore, pathogens and symbionts depend on similar mechanisms for interacting with hosts and show parallel trends in genome evolution.

Animals↗

Evolution of genes for allelic and isotypic forms of immunoglobulin kappa chains and of the genes for T-cell receptor beta chains in rabbits.

New insights into the evolution of the families of genes encoding immunoglobulins and T-cell receptors of rabbits (Oryctolagus cuniculus) have come from molecular genetic studies. In contrast to human and mouse, rabbits were shown to have two genes for the constant region of immunoglobulin light chains (C kappa 1 and C kappa 2 isotypes) and complex allelic variants of K1 (allotypes). Although K1 allotype protein sequences differed at up to 41% of the amino acid positions, 3' untranslated, 5', and 3' flanking regions were conserved, and in the coding regions 78-80% of the codons with differences had replacement changes. Proportions of silent changes and changes in noncoding regions were comparable. Thus, in spite of their markedly different protein sequences, the K1b4, b5, and b9 allotypes appeared to be products of allelic genes. Molecular genetic analyses suggested that they may have undergone rapid divergence after an ancestral K2-like gene duplicated. Some rabbits were found to have two similar T-cell receptor C beta genes as do humans and many strains of mice, but others appeared to have three different C beta. In addition, we found allotypic forms of C beta. Some of the C beta allotypic differences occurred at positions where analogous C kappa allotypic differences were found. We also found V beta in mouse and human that were more similar to rabbit V beta than closely linked rabbit genes were to each other. This contrasts with rabbit immunoglobulin VH gene sequences that reflect concerted evolution. The data suggested that T-cell receptor V beta genes duplicated prior to mammalian radiation.

Alleles↗

Further examples of evolution by gene duplication revealed through DNA sequence comparisons.

To test the theory that evolution by gene duplication occurs as a result of positive Darwinian selection that accompanies the acceleration of mutant substitutions, DNA sequences of recent duplication were analyzed by estimating the numbers of synonymous and nonsynonymous substitutions. For the troponin C family, at the period of differentiation of the fast and slow isoforms, amino acid substitutions were shown to have been accelerated relative to synonymous substitutions. Comparison of the first exon of alpha-actin genes revealed that amino acid substitutions were accelerated when the smooth muscle, skeletal and cardiac isoforms differentiated. Analysis of members of the heat shock protein 70 gene family of mammals indicates that heat shock responsive genes including duplicated copies are evolving rapidly, contrary to the cognitive genes which have been evolutionarily conservative. For the alpha 1-antitrypsin reactive center, the acceleration of amino acid substitution has been found for gene paris of recent duplication.

Actins↗

Modern evolution of a single-copy gene: the immunoglobulin C kappa locus in wild mice.

The immunoglobulin kappa light-chain constant region gene (C kappa) has been cloned and sequenced from five wild mouse species. Analysis of these data has permitted an assessment of single-copy gene evolution during a limited time period as defined by the genus Mus. Sequence conservation was found to be as high (or higher) in the 5' and enhancer regions as in the coding region. The pattern of substitutions throughout these genes suggests that parallel evolution has occurred frequently and that substitutions at replacement sites have not decreased significantly, owing to saturation during this period of approximately 10 Myr. Phylogenetic relationships have been determined among these wild species as well as among members of the genus Rattus.

Animals↗

Energy constraints on the evolution of gene expression.

I here estimate the energy cost of changes in gene expression for several thousand genes in the yeast Saccharomyces cerevisiae. A doubling of gene expression, as it occurs in a gene duplication event, is significantly selected against for all genes for which expression data is available. It carries a median selective disadvantage of s > 10(-5), several times greater than the selection coefficient s = 1.47 x 10(-7) below which genetic drift dominates a mutant's fate. When considered separately, increases in messenger RNA expression or protein expression by more than a factor 2 also have significant energy costs for most genes. This means that the evolution of transcription and translation rates is not an evolutionarily neutral process. They are under active selection opposing them. My estimates are based on genome-scale information of gene expression in the yeast S. cerevisiae as well as information on the energy cost of biosynthesizing amino acids and nucleotides.

Amino Acids↗

The evolution of gene regulation by transcription factors and microRNAs.

Changes in the patterns of gene expression are widely believed to underlie many of the phenotypic differences within and between species. Although much emphasis has been placed on changes in transcriptional regulation, gene expression is regulated at many levels, all of which must ultimately be studied together to obtain a complete picture of the evolution of gene expression. Here we compare the evolution of transcriptional regulation and post-transcriptional regulation that is mediated by microRNAs, a large class of small, non-coding RNAs in plants and animals, focusing on the evolution of the individual regulators and their binding sites. As an initial step towards integrating these mechanisms into a unified framework, we propose a simple model that describes the transcriptional regulation of new microRNA genes.

Computational Biology↗

Isolation and mapping the chicken zona pellucida genes: an insight into the evolution of orthologous genes in different species.

The avian oocyte is surrounded by a specialized extracellular glycoproteinaceous matrix, the perivitelline membrane, which is equivalent to the zona pellucida (ZP) in mammals and the chorion in teleosts. A number of related ZP genes encode the proteins that make up this matrix. These proteins play an important role in the sperm/egg interaction and may be involved in speciation. The human genome is known to contain ZP1, ZP2, ZP3, and ZPB genes, while a ZPAX gene has also been identified in Xenopus. The rapid evolution of these genes has confused the nomenclature and thus orthologous relationships across species. In order to clarify these homologies, we have identified ZP1, ZP2, ZPC, ZPB, and ZPAX genes in the chicken and mapped them to chromosomes 5, 14, 10, 6, and 3, respectively, establishing conserved synteny with human and mouse. The amino acid sequences of these genes were compared to the orthologous genes in human, mouse, and Xenopus, and have given us an insight into the evolution of these genes in a variety of different species. The presence of the ZPAX gene in the chicken has highlighted a pattern of probable gene loss by deletion in mouse and gene inactivation by deletion, and base substitution in human.

Amino Acid Sequence↗

Evolution by gene duplication and compensatory advantageous mutations.

Relaxation of selective constraint is thought to play an important role for evolution by gene duplication, in connection with compensatory advantageous mutant substitutions. Models were investigated by incorporating gene duplication by unequal crossing over, selection, mutation and random genetic drift into Monte Carlo simulations. Compensatory advantageous mutations were introduced, and simulations were carried out with and without relaxation, when genes are redundant on chromosomes. Relaxation was introduced by assuming that deleterious mutants have no effect on fitness, so long as one or more genes free of such mutations remain in the array. Compensatory mutations are characterized by the intermediate deleterious step of their substitutions, and therefore relaxation by gene redundancy is important. Through extensive Monte Carlo simulations, it was found that compensatory mutant substitutions require relaxation in addition to gene duplication, when mutant effects are large. However when mutant effects are small, such that the product of selection coefficient and population size is around unity, evolution by compensatory mutation is enhanced by gene duplication even without relaxation.

Biological Evolution↗

Prevalence of intron gain over intron loss in the evolution of paralogous gene families.

The mechanisms and evolutionary dynamics of intron insertion and loss in eukaryotic genes remain poorly understood. Reconstruction of parsimonious scenarios of gene structure evolution in paralogous gene families in animals and plants revealed numerous gains and losses of introns. In all analyzed lineages, the number of acquired new introns was substantially greater than the number of lost ancestral introns. This trend held even for lineages in which vertical evolution of genes involved more intron losses than gains, suggesting that gene duplication boosts intron insertion. However, dating gene duplications and the associated intron gains and losses based on the molecular clock assumption showed that very few, if any, introns were gained during the last approximately 100 million years of animal and plant evolution, in agreement with previous conclusions reached through analysis of orthologous gene sets. These results are generally compatible with the emerging notion of intensive insertion and loss of introns during transitional epochs in contrast to the relative quiet of the intervening evolutionary spans.

Amino Acid Sequence↗

Tracing the evolution of gene loss in obligate bacterial symbionts.

The gamma-proteobacterial symbionts of insects are a model group for comparative studies of genome reduction. The phylogenetic proximity of these reduced genomes to the larger genomes of well-studied free-living bacteria has enabled reconstructions of the process by which genes and DNA are lost. Three genome sequences are now available for Buchnera aphidicola. Analyses of Buchnera genomes in comparison with those of related enteric bacteria suggest that extensive changes including large deletions, repetitive element proliferation and chromosomal rearrangements occurred initially, followed by extreme stasis in gene order and slow decay of additional genes. This pattern appears to be characteristic of symbiont evolution.

Biological Evolution↗