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PubMed2003

Genetic evolution of alpha fetoprotein producing gastric cancer.

BACKGROUND: Alpha fetoprotein (AFP) producing gastric cancer is an unusual form of aggressive adenocarcinoma with a complex histological picture, including enteroblastic and hepatoid differentiation. AIMS: To investigate the genetic events underlying the phenotypic diversity in AFP producing gastric cancer and the ability of these tumours to produce AFP ectopically. METHODS: Multiple foci from 19 AFP producing gastric adenocarcinomas were microdissected and loss of heterozygosity (LOH) analysis was performed with a panel of microsatellite markers on nine chromosomal arms. RESULTS: For informative cases, LOH was most frequently detected on 17p (100%), followed by 13q (88%), 3p (87%), 5q and 9p (80%), 11q (70%), 18q (58%), 16q (53%), and 8p (50%). The average fractional allelic loss was 0.72. LOH was detected either homogeneously throughout the microdissected foci, or only in some parts of the neoplastic foci for each case. Heterogeneous patterns of LOH indicated genetic progression and/or divergence in clonal evolution. Furthermore, in six cases with heterogeneous LOH of 13q, 13q LOH was restricted to immunohistochemically AFP positive neoplastic foci. CONCLUSION: AFP-GC arises as an aggressive clone with extensive LOH and high fractional allelic loss. The presence of heterogeneous patterns of LOH suggested that the AFP producing carcinoma foci might evolve through genetic progression and/or genetic divergence. Silencing of the crucial gene on 13q may be involved in the acquisition of the AFP producing phenotype.

Adult↗
PubMed2000

Evolution of temporal isolation in the wild: genetic divergence in timing of migration and breeding by introduced chinook salmon populations.

The timing of migration and breeding are key life-history traits; they are not only adaptations of populations to their environments, but can serve to increase reproductive isolation, facilitating further divergence among populations. As part of a study of divergence of chinook salmon, Oncorhynchus tshawytscha, populations, established in New Zealand from a common source in the early 1900s, we tested the hypotheses that the timing of migration and breeding are under genetic control and that the populations genetically differ in these traits despite phenotypic overlap in timing in the wild. Representatives of families from two populations were collected within a day or two of each other, reared in a common environment, and then released to sea from each of two different rivers, while other family representatives were retained in fresh water to maturity. The date of maturation of fish held in fresh water and the dates of return from the ocean and maturation of fish released to sea all showed significant differences between the two populations and among families within populations. The very high heritabilities and genetic correlations estimated for migration and maturation date indicated that these traits would respond rapidly to selection. Combined with the results of related studies on these chinook salmon populations, it appears that spawning time may not only evolve during the initial phases of divergence, but it may play an important role in accelerating divergence in other traits.

Animals↗
PubMed2001

Mutation processes at the protein level: is Lamarck back?

The experimental evidence accumulated for the last half of the century clearly suggests that inherited variation is not restricted to the changes in genomic sequences. The prion model, originally based on unusual transmission of certain neurodegenerative diseases in mammals, provides a molecular mechanism for the template-like reproduction of alternative protein conformations. Recent data extend this model to protein-based genetic elements in yeast and other fungi. Reproduction and transmission of yeast protein-based genetic elements is controlled by the "prion replication" machinery of the cell, composed of the protein helpers responsible for the processes of assembly and disassembly of protein structures and multiprotein complexes. Among these, the stress-related chaperones of Hsp100 and Hsp70 groups play an important role. Alterations of levels or activity of these proteins result in "mutator" or "antimutator" affects in regard to protein-based genetic elements. "Protein mutagens" have also been identified that affect formation and/or propagation of the alternative protein conformations. Prion-forming abilities appear to be conserved in evolution, despite the divergence of the corresponding amino acid sequences. Moreover, a wide variety of proteins of different origins appear to possess the ability to form amyloid-like aggregates, that in certain conditions might potentially result in prion-like switches. This suggests a possible mechanism for the inheritance of acquired traits, postulated in the Lamarckian theory of evolution. The prion model also puts in doubt the notion that cloned animals are genetically identical to their genome donors, and suggests that genome sequence would not provide a complete information about the genetic makeup of an organism.

Animals↗
PubMed1997

Intermittent divergence of the protein tyrosine kinase family during animal evolution.

The protein tyrosine kinases (PTKs) are a large protein family consisting of many subfamilies with a variety of domain structures. The basic functions are thought to differ for different subfamilies. To know the dates at which the subfamilies diverged by gene duplications, a phylogenetic tree of the PTKs was inferred by comparing sequences from a wide range of species covering diploblasts and triploblasts. The PTK tree revealed that almost all of the gene duplications that gave rise to different subfamilies occurred rapidly before the diploblast-triploblast split, accompanying with rapid amino acid substitutions. This type of gene duplication was, however, rarely observed after that split. Long after the subfamily divergence, another type of gene duplication that gave rise to diverse tissue-specific genes occurred in each subfamily on the chordate lineage since the separation from arthropods. This type of gene duplication occurred frequently before the fish-tetrapod split, accompanying with rapid amino acid substitutions. In contrast, both the frequency of gene duplications and the rate of the amino acid substitutions were considerably reduced after that split. These results strongly suggest that the PTKs diverged intermittently, but not gradually, during animal evolution.

Amino Acids↗
PubMed2004

Life-history divergence in Chinook salmon: historic contingency and parallel evolution.

By jointly considering patterns of genetic and life-history diversity in over 100 populations of Chinook salmon from California to British Columbia, we demonstrate the importance of two different mechanisms for life-history evolution. Mapping adult run timing (the life-history trait most commonly used to characterize salmon populations) onto a tree based on the genetic data shows that the same run-time phenotypes exist in many different genetic lineages. In a hierarchical gene diversity analysis, differences among major geographic and ecological provinces explained the majority (62%) of the overall G(ST), whereas run-time differences explained only 10%. Collectively, these results indicate that run-timing diversity has developed independently by a process of parallel evolution in many different coastal areas. However, genetic differences between coastal populations with different run timing from the same basin are very modest (G(ST) < 0.02), indicating that evolutionary divergence of this trait linked to reproductive isolation has not led to parallel speciation, probably because of ongoing gene flow. A strikingly different pattern is seen in the interior Columbia River Basin, where run timing and other correlated life-history traits map cleanly onto two divergent genetic lineages (G(ST) approximately 0.15), indicating that some patterns of life-history diversity have a much older origin. Indeed, genetic data indicate that in the interior Columbia Basin, the two divergent lineages behave essentially as separate biological species, showing little evidence of genetic contact in spite of the fact that they comigrate through large areas of the river and ocean and in some locations spawn in nearly adjacent areas.

Animal Migration↗
PubMed2005

Adaptive evolution after gene duplication in alpha-KT x 14 subfamily from Buthus martensii Karsch.

A series of isoforms of alpha-KT x 14 (short chain potassium channel scorpion toxins) were isolated from the venom of Buthus martensii Karsch by RACE and screening cDNA library methods. These isoforms adding BmKK1--3 and BmSKTx1--2 together shared high homology (more than 97%) with each other. The result of genomic sequence analysis showed that a length 79 bp intron is inserted Ala codes between the first and the second base at the 17th amino acid of signal peptide. The introns of these isoforms also share high homology with those of BmKK2 and BmSKT x 1 reported previously. Sequence analysis of many clones of cDNA and genomic DNA showed that a species population or individual polymorphism of alpha-KT x 14 genes took place in scorpion Buthus martensii Karsch and accelerated evolution played an important role in the forming process of alpha-KT x 14 scorpion toxins subfamily. The result of southern hybridization indicated that alpha-KT x 14 toxin genes existed in scorpion chromosome with multicopies. All findings maybe provided an important evidence for an extensive evolutionary process of the scorpion "pharmacological factory": at the early course of evolution, the ancestor toxic gene duplicated into a series of multicopy genes integrated at the different chromosome; at the late course of evolution, subsequent functional divergence of duplicate genes was generated by mutations, deletions and insertion.

Adaptation, Physiological↗
PubMed2006

Molecular and functional evolution of Tetrahymena metallothioneins: new insights into the gene family of Tetrahymena thermophila.

A new metallothionein (MTT-5) gene isoform has been cloned and characterized from the ciliate Tetrahymena thermophila. Its amino acid sequence shows only limited similarity with other Tetrahymena MTs. To investigate the transcriptional activity of this gene toward heavy metals (Cd, Cu, Zn), mRNA levels were evaluated by real-time quantitative PCR. Results show that the three metals induce different MTT-5-mRNA levels, Cd treatment eliciting the most effective induction in the first 30 min. Phylogenetic analyses of all Tetrahymena MT protein sequences revealed that MTT-5 is closely related to Cd-induced isoforms and quite separate from Cu-induced ones. Our results indicate that Cd and Cu MTs diverged early in evolution, before the speciation event which separated the Tetrahymena borealis group from the Tetrahymena australis group. The mutation rate in the Tetrahymena MT group is heterogeneous, being very low for MT-1 and MTT-1 and higher for the other isoforms, particularly for MTT-5, which shows the maximum divergence among the Cd-induced MTs. This observation, together with the evidence of its inducibility by Zn - a unique condition among T. thermophila MTs - indicates that MTT-5 underwent a particular evolutionary history, independent of other MT isoforms.

Amino Acid Sequence↗
PubMed1988

The right to refuse treatment with antipsychotic medications: retrospect and prospect.

The right to refuse antipsychotic medication is now more than a decade old. Its evolution has taken divergent forms, driven either by the needs of patients' treatment or the mandate of patients' rights. Regardless of the model employed, refusal is not uncommon, but refusing patients appear almost always to receive treatment in the end. These findings point up the essential illogic of allowing committed persons to refuse treatment that would permit their freedom to be restored. The future evolution of the right may proceed differently in federal and state courts, but whether at the level of legal theory or actual practice, some accommodation will restore the equivalence between the power to commit and the power to treat.

Commitment of Persons with Psychiatric Disorders↗
PubMed2002

Ty1 /copia- and Ty3 /gypsy-like DNA sequences in Helianthus species.

Two repeated DNA sequences isolated from a partial genomic DNA library of Helianthus annuus, p HaS13 and p HaS211, were shown to represent portions of the int gene of a Ty3 /gypsy retroelement and of the RNase-Hgene of a Ty1 /copia retroelement, respectively. Southern blotting patterns obtained by hybridizing the two probes to BglII- or DraI-digested genomic DNA from different Helianthus species showed p HaS13 and p HaS211 were parts of dispersed repeats at least 8 and 7 kb in length, respectively, that were conserved in all species studied. Comparable hybridization patterns were obtained in all species with p HaS13. By contrast, the patterns obtained by hybridizing p HaS211 clearly differentiated annual species from perennials. The frequencies of p HaS13- and p HaS211-related sequences in different species were 4.3x10(4)-1.3x10(5) copies and 9.9x10(2)-8.1x10(3) copies per picogram of DNA, respectively. The frequency of p HaS13-related sequences varied widely within annual species, while no significant difference was observed among perennial species. Conversely, the frequency variation of p HaS211-related sequences was as large within annual species as within perennials. Sequences of both families were found to be dispersed along the length of all chromosomes in all species studied. However, Ty3 /gypsy-like sequences were localized preferentially at the centromeric regions, whereas Ty1/ copia-like sequences were less represented or absent around the centromeres and plentiful at the chromosome ends. These findings suggest that the two sequence families played a role in Helianthusgenome evolution and species divergence, evolved independently in the same genomic backgrounds and in annual or perennial species, and acquired different possible functions in the host genomes.

Amino Acid Sequence↗
PubMed2006

[Progress in the study of gene duplication].

Gene duplication is one of the most important factors that influence the evolution of genome size, the origination of novel gene, the genetic robustness against null mutations, the speciation, etc. Duplication can be created by unequal crossing over, retroposition, or whole genome (or chromosomal) duplication. In this review, we summarized the studies of the molecular mechanisms of gene duplication, the preservation of duplicated gene, the selections acting on duplicated gene, the alternative ways of divergence and the evolution rate.

Animals↗
PubMed2005

Structural and functional divergence of MutS2 from bacterial MutS1 and eukaryotic MSH4-MSH5 homologs.

MutS homologs, identified in nearly all bacteria and eukaryotes, include the bacterial proteins MutS1 and MutS2 and the eukaryotic MutS homologs 1 to 7, and they often are involved in recognition and repair of mismatched bases and small insertion/deletions, thereby limiting illegitimate recombination and spontaneous mutation. To explore the relationship of MutS2 to other MutS homologs, we examined conserved protein domains. Fundamental differences in structure between MutS2 and other MutS homologs suggest that MutS1 and MutS2 diverged early during evolution, with all eukaryotic homologs arising from a MutS1 ancestor. Data from MutS1 crystal structures, biochemical results from MutS2 analyses, and our phylogenetic studies suggest that MutS2 has functions distinct from other members of the MutS family. A mutS2 mutant was constructed in Helicobacter pylori, which lacks mutS1 and mismatch repair genes mutL and mutH. We show that MutS2 plays no role in mismatch or recombinational repair or deletion between direct DNA repeats. In contrast, MutS2 plays a significant role in limiting intergenomic recombination across a range of donor DNA tested. This phenotypic analysis is consistent with the phylogenetic and biochemical data suggesting that MutS1 and MutS2 have divergent functions.

Adenosine Triphosphatases↗
PubMed2002

Evolution of dinoflagellate unigenic minicircles and the partially concerted divergence of their putative replicon origins.

Dinoflagellate chloroplast genes are unique in that each gene is on a separate minicircular chromosome. To understand the origin and evolution of this exceptional genomic organization we completely sequenced chloroplast psbA and 23S rRNA gene minicircles from four dinoflagellates: three closely related Heterocapsa species (H. pygmaea, H. rotundata, and H. niei) and the very distantly related Amphidinium carterae. We also completely sequenced a Protoceratium reticulatum minicircle with a 23S rRNA gene of novel structure. Comparison of these minicircles with those previously sequenced from H. triquetra and A. operculatum shows that in addition to the single gene all have noncoding regions of approximately a kilobase, which are likely to include a replication origin, promoter, and perhaps segregation sequences. The noncoding regions always have a high potential for folding into hairpins and loops. In all six dinoflagellate strains for which multiple minicircles are fully sequenced, parts of the noncoding regions, designated cores, are almost identical between the psbA and 23S rRNA minicircles, but the remainder is very different. There are two, three, or four cores per circle, sometimes highly related in sequence, but no sequence identity is detectable between cores of different species, even within one genus. This contrast between very high core conservation within a species, but none among species, indicates that cores are diverging relatively rapidly in a concerted manner. This is the first well-established case of concerted evolution of noncoding regions on numerous separate chromosomes. It differs from concerted evolution among tandemly repeated spacers between rRNA genes, and that of inverted repeats in plant chloroplast genomes, in involving only the noncoding DNA cores. We present two models for the origin of chloroplast gene minicircles in dinoflagellates from a typical ancestral multigenic chloroplast genome. Both involve substantial genomic reduction and gene transfer to the nucleus. One assumes differential gene deletion within a multicopy population of the resulting oligogenic circles. The other postulates active transposition of putative replicon origins and formation of minicircles by homologous recombination between them.

Animals↗
PubMed2001

Performance of a divergence time estimation method under a probabilistic model of rate evolution.

Rates of molecular evolution vary over time and, hence, among lineages. In contrast, widely used methods for estimating divergence times from molecular sequence data assume constancy of rates. Therefore, methods for estimation of divergence times that incorporate rate variation are attractive. Improvements on a previously proposed Bayesian technique for divergence time estimation are described. New parameterization more effectively captures the phylogenetic structure of rate evolution on a tree. Fossil information and other evidence can now be included in Bayesian analyses in the form of constraints on divergence times. Simulation results demonstrate that the accuracy of divergence time estimation is substantially enhanced when constraints are included.

Bayes Theorem↗
PubMed2007

A structure-centric view of protein evolution, design, and adaptation.

Proteins, by virtue of their central role in most biological processes, represent one of the key subjects of the study of molecular evolution. Inherent in the indispensability of proteins for living cells is the fact that a given protein can adopt a specific three-dimensional shape that is specified solely by the protein's sequence of amino acids. Over the past several decades, structural biologists have demonstrated that the array of structures that proteins may adopt is quite astounding, and this has lead to a strong interest in understanding how protein structures change and evolve over time. In this review we consider a large body of recent work that attempts to illuminate this structure-centric picture of protein evolution. Much of this work has focused on the question of how completely new protein structures (i.e., new folds or topologies) are discovered by protein sequences as they evolve. Pursuant to this question of structural innovation has been a desire to describe and understand the observation that certain types of protein structures are far more abundant than others and how this uneven distribution of proteins implicates on the process through which new shapes are discovered. We consider a number of theoretical models that have been successful at explaining this heterogeneity in protein populations and discuss the increasing amount of evidence that indicates that the process of structural evolution involves the divergence of protein sequences and structures from one another. We also consider the topic of protein designability, which concerns itself with understanding how a protein's structure influences the number of sequences that can fold successfully into that structure. Understanding and quantifying the relationship between the physical feature of a structure and its designability has been a long-standing goal of the study of protein structure and evolution, and we discuss a number of recent advances that have yielded a promising answer to this question. Finally, we review the relatively new field of protein structural phylogeny, an area of study in which information about the distribution of protein structures among different organisms is used to reconstruct the evolutionary relationships between them. Taken together, the work that we review presents an increasingly coherent picture of how these unique polymers have evolved over the course of life on Earth.

Adaptation, Biological↗
PubMed2001

Human 5-HT(5) receptors: the 5-HT(5A) receptor is functional but the 5-HT(5B) receptor was lost during mammalian evolution.

We have isolated from a human genomic library the human 5-hydroxytryptamine 5-HT(5A) and 5-HT(5B) genes. The human 5-HT(5A) gene encodes a protein with similar characteristics to its mouse homologue. When expressed in monkey COS-7 cells, the human 5-HT(5A) receptor displayed a high affinity for tritiated 5-carbamidotryptamine ([3H]5-CT; K(D)=2.8 nM) and iodinated lysergic acid diethylamide ([125I]LSD; K(D)=187 pM). These binding sites displayed the following displacement profile: Ergotamine>Methiothepin>5-CT, Ritanserin>5-HT. Reverse transcriptase polymerase chain reaction (RT-PCR) experiments revealed the presence of human 5-HT(5A) mRNA in the central nervous system but not in peripheral organs. When expressed in Xenopus oocytes, the 5-HT(5A) receptor was able to couple to the inwardly rectifying K(+) channel, GIRK(1). In contrast to the human 5-HT(5A) gene and the mouse 5-HT(5B) gene, the human 5-HT(5B) gene does not encode a functional protein because its coding sequence is interrupted by stop codons. Our results suggest, therefore, that the 5-HT(5B) receptor has been lost during evolution after the divergence between rodents and primates. The 5-HT(5B) receptor is the first example of a brain-specific protein that is absent in human.

3T3 Cells↗
PubMed2005

Structural evolution of the protein kinase-like superfamily.

The protein kinase family is large and important, but it is only one family in a larger superfamily of homologous kinases that phosphorylate a variety of substrates and play important roles in all three superkingdoms of life. We used a carefully constructed structural alignment of selected kinases as the basis for a study of the structural evolution of the protein kinase-like superfamily. The comparison of structures revealed a "universal core" domain consisting only of regions required for ATP binding and the phosphotransfer reaction. Remarkably, even within the universal core some kinase structures display notable changes, while still retaining essential activity. Hence, the protein kinase-like superfamily has undergone substantial structural and sequence revision over long evolutionary timescales. We constructed a phylogenetic tree for the superfamily using a novel approach that allowed for the combination of sequence and structure information into a unified quantitative analysis. When considered against the backdrop of species distribution and other metrics, our tree provides a compelling scenario for the development of the various kinase families from a shared common ancestor. We propose that most of the so-called "atypical kinases" are not intermittently derived from protein kinases, but rather diverged early in evolution to form a distinct phyletic group. Within the atypical kinases, the aminoglycoside and choline kinase families appear to share the closest relationship. These two families in turn appear to be the most closely related to the protein kinase family. In addition, our analysis suggests that the actin-fragmin kinase, an atypical protein kinase, is more closely related to the phosphoinositide-3 kinase family than to the protein kinase family. The two most divergent families, alpha-kinases and phosphatidylinositol phosphate kinases (PIPKs), appear to have distinct evolutionary histories. While the PIPKs probably have an evolutionary relationship with the rest of the kinase superfamily, the relationship appears to be very distant (and perhaps indirect). Conversely, the alpha-kinases appear to be an exception to the scenario of early divergence for the atypical kinases: they apparently arose relatively recently in eukaryotes. We present possible scenarios for the derivation of the alpha-kinases from an extant kinase fold.

Adenosine Triphosphate↗
PubMed1994

Molecular cloning of a lamprey homologue of the mammalian MHC class III gene, complement factor B.

To elucidate the origin and evolution of the complement system and the MHC, we isolated cDNA clones for the MHC class III complement factor B (Bf) gene from lamprey, one of the most primitive extant vertebrates. A part of the serine protease domain of the lamprey Bf was amplified by reverse transcriptase-PCR using the degenerated primers corresponding to the conserved amino acid stretches between the mouse Bf and C2 sequences. A full-length lamprey Bf cDNA clone was isolated from the lamprey liver cDNA library using a PCR-amplified DNA clone as a probe. The deduced amino acid sequence of 763 residues showed essentially the same domain structure as mammalian Bf or C2, consisting of three short consensus repeat domains, a von Willebrand domain, and a serine protease domain. Lamprey Bf showed 33 and 29% overall amino acid similarity to mouse Bf and mouse C2, respectively, whereas amino acid similarity between mouse Bf and mouse C2 was 36%, suggesting that the gene duplication of Bf/C2 occurred in the main line of vertebrate evolution after the divergence of cyclostomes. This is the first report of the molecular cloning from cyclostomes of a component of the mammalian MHC that offers the possibility of genetic analysis of the presumably primitive MHC of cyclostomes.

Amino Acid Sequence↗
PubMed2005

Structural analysis of Escherichia coli ThiF.

Escherichia coli ThiF is an enzyme in the biosynthetic cascade for generating the essential cofactor thiamin pyrophosphate. In this cascade, ThiF catalyzes adenylation of the C terminus of ThiS. We report here the crystal structures of ThiF, alone and in complex with ATP. The structures provide insight into a preference for ATP during adenylation of the protein ThiS. Additionally, the structures reveal an ordered crossover loop predicted to clamp the flexible tail of ThiS into the ThiF active site during the adenylation reaction. The importance of the crossover loop for ThiF activity is highlighted by mutational analysis. Comparison of ThiF with the structural homologues MoeB, APPBP1-UBA3, and SAE1-SAE2 reveals that the ATP-binding site, including an arginine-finger, is maintained throughout evolution, and shows divergence occurring in protein substrate-binding sites and regions devoted to unique steps in the specific function of each enzyme.

Adenosine Triphosphate↗