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Evolutionary diversification of cranial and spinal nerves and their targets in the gymnophione amphibians.

The ancestral gymnophione (caecilian) became elongate and limbless early in its history. Further structural reduction, including loss of components, followed by redirection and occasionally cooption of remaining structures, particularly muscles and nerves, has evolved. Function may remain that of the ancestral condition, or may change dramatically. Examples include the evolution of the tentacle, the jaw-closing apparatus, and the hypobranchial musculature, including their innervation. 'Regressive' evolution has provided opportunity for new structural-functional relationships and for increased variation.

Amphibians↗

Evolution of genetic codes through isologous diversification of cellular states.

Evolution of genetic codes is studied as change in the choice of enzymes that are used to synthesize amino acids from the genetic information of nucleic acids. We propose the following theory: the differentiation of physiological states of a cell allows for a choice of enzymes, and this choice is later fixed genetically through evolution. To demonstrate this theory, a dynamical systems model consisting of the concentrations of metabolites, enzymes, amino acyl tRNA synthetase, and tRNA - amino acid complexes in a cell is introduced and studied numerically. It is shown that the biochemical states of cells are differentiated by cell-cell interactions, and each differentiated type starts to use a different synthetase. Through the mutation of genes, this difference in the genetic code is amplified and stabilized. The relevance of this theory to the evolution of non-universal genetic code in mitochondria is suggested. The present theory is based on our recent theory of isologous symbiotic speciation, which is briefly reviewed. According to the theory, phenotypes of organisms are first differentiated into distinct types through the interaction and developmental dynamics, even though they have identical genotypes; later, with mutation in the genotype, the genotype also differentiates into discrete types, while maintaining the "symbiotic" relationship between the types. Relevance of the theory to natural as well as artificial evolution is discussed.

Biological Clocks↗

The nature of diversity and diversification at the ABO locus.

In this study we analyzed the complete genomic sequences, except intron 1, and 2 regulatory regions of 6 common (ABO*A101, ABO*A201, ABO*B101, ABO*O01, ABO*O02, and ABO*O03) and 18 rare ABO alleles, 3 of which were new. This was done by phylogenetic analysis and correlating sequence data with the ABO phenotypes. The study revealed multiple polymorphisms in noncoding regions. The intron-based phylogenetic analysis revealed 5 main lineages: ABO*A, ABO*B, ABO*O01, ABO*O02, and ABO*O03. The genomic sequences of most rare ABO alleles differed slightly from those of the common alleles. Singular mutations or hybrid alleles were most common, but a few exhibited mosaic sequence pattern containing multiple exon and/or intron motifs from other ABO lineages. Thus, both an accumulation of mutations as well as an assortment of the mutations by recombination seems to be responsible for the ABO gene diversity. The prevalence of replacement mutations indicates positive selection for allelic diversity. Phenotype-genotype correlation showed that sequence variations within the complete coding sequence can affect A- and B-antigen expression. All variant ABO*A/B alleles and one new ABO*O03-like allele were associated with weak ABO phenotypes. These findings are suggestive of the requirement of a comprehensive coding sequence database for sequence-based phenotype prediction.

ABO Blood-Group System↗

Codon insertion and deletion functions as a somatic diversification mechanism in human antibody repertoires.

UNLABELLED: It has been suggested that codon insertion and/or deletion may represent a mechanism that, along with hypermutation, contributes to the affinity maturation of antibodies. We used repertoire cloning to examine human antibodies directed against 3 carbohydrate antigens and 1 protein antigen for the presence of such modifications. We find that both the insertion and deletion of codons occur frequently in antigen-specific responses following vaccination. Codon insertions and deletions were observed most often in the complementarity determining regions, and less frequently in the framework regions, of VH, Vkappa, and Vlambda gene segments, and involved motifs known to be preferred targets of somatic hypermutation. Clonal lineage analysis shows that these events occur through out the course of the somatic maturation of individual antibody clones. We also determined that these alterations of paratope structure have varying effects on the relative affinity of the binding site for its cognate antigen. REVIEWERS: This article was reviewed by Mark Shlomchik, Deborah Dunn-Walters (nominated by Dr. Andrew Macpherson), and Rachel M. Gerstein. OPEN PEER REVIEW: Reviewed by Mark Shlomchik, Deborah Dunn-Walters (nominated by Dr. Andrew Macpherson), and Rachel M. Gerstein. For the full reviews, please go to the Reviewers' comments section.

Journal Article↗

Tyrosine kinase signalling in breast cancer. Epidermal growth factor receptor: convergence point for signal integration and diversification.

Cross-communication between different signalling systems is critical for the integration of multiple and changing environmental influences on individual cells. The epidermal growth factor receptor (EGFR) has been identified as a key element in the complex signalling network that is utilized by various classes of cell-surface receptors. This nonclassical mode of signalling system cross-talk, in distinction to receptor activation induced by cognate ligands, has been termed 'signal transactivation'. With the EGFR as the convergence point and distribution focus, this scenario may involve signals emitted by other members of the tyrosine kinase family, cytokine receptors, ion channels, G-protein-coupled receptors and integrins.

Breast↗

Multiple adenosine 3',5'-cyclic [corrected] monophosphate response element DNA-binding proteins generated by gene diversification and alternative exon splicing.

The protein sequence deduced from the open reading frame of a human placental cDNA encoding a cAMP-responsive enhancer (CRE)-binding protein (CREB-327) has structural features characteristic of several other transcriptional transactivator proteins including jun, fos, C/EBP, myc, and CRE-BP1. Results of Southwestern analysis of nuclear extracts from several different cell lines show that there are multiple CRE-binding proteins, which vary in size in cell lines derived from different tissues and animal species. To examine the molecular diversity of CREB-327 and related proteins at the nucleic acid level, we used labeled cDNAs from human placenta that encode two different CRE-binding proteins (CREB-327 and CRE-BP1) to probe Northern and Southern blots. Both probes hybridized to multiple fragments on Southern blots of genomic DNA from various species. Alternatively, when a human placental c-jun probe was hybridized to the same blot, a single fragment was detected in most cases, consistent with the intronless nature of the human c-jun gene. The CREB-327 probe hybridized to multiple mRNAs, derived from human placenta, ranging in size from 2-9 kilobases. In contrast, the CRE-BP1 probe identified a single 4-kilobase mRNA. Sequence analyses of several overlapping human genomic cosmid clones containing CREB-327 sequences in conjunction with polymerase chain reaction indicates that the CREB-327/341 cDNAs are composed of at least eight or nine exons, and analyses of human placental cDNAs provide direct evidence for at least one alternatively spliced exon. Analyses of mouse/hamster-human hybridoma DNAs by Southern blotting and polymerase chain reaction localizes the CREB-327/341 gene to human chromosome 2. The results indicate that there is a dichotomy of CREB-like proteins, those that are related by overall structure and DNA-binding specificity as well as those that are related by close similarities of primary sequences.

Amino Acid Sequence↗

Evolutionary diversification of pigment pattern in Danio fishes: differential fms dependence and stripe loss in D. albolineatus.

The developmental bases for species differences in adult phenotypes remain largely unknown. An emerging system for studying such variation is the adult pigment pattern expressed by Danio fishes. These patterns result from several classes of pigment cells including black melanophores and yellow xanthophores, which differentiate during metamorphosis from latent stem cells of presumptive neural crest origin. In the zebrafish D. rerio, alternating light and dark horizontal stripes develop, in part, owing to interactions between melanophores and cells of the xanthophore lineage that depend on the fms receptor tyrosine kinase; zebrafish fms mutants lack xanthophores and have disrupted melanophore stripes. By contrast, the closely related species D. albolineatus exhibits a uniform pattern of melanophores, and previous interspecific complementation tests identified fms as a potential contributor to this difference between species. Here, we survey additional species and demonstrate marked variation in the fms-dependence of hybrid pigment patterns, suggesting interspecific variation in the fms pathway or fms requirements during pigment pattern formation. We next examine the cellular bases for the evolutionary loss of stripes in D. albolineatus and test the simplest model to explain this transformation, a loss of fms activity in D. albolineatus relative to D. rerio. Within D. albolineatus, we demonstrate increased rates of melanophore death and decreased melanophore migration, different from wild-type D. rerio but similar to fms mutant D. rerio. Yet, we also find persistent fms expression in D. albolineatus and enhanced xanthophore development compared with wild-type D. rerio, and in stark contrast to fms mutant D. rerio. These findings exclude the simplest model in which stripe loss in D. albolineatus results from a loss of fms-dependent xanthophores and their interactions with melanophores. Rather, our results suggest an alternative model in which evolutionary changes in pigment cell interactions themselves have contributed to stripe loss, and we test this model by manipulating melanophore numbers in interspecific hybrids. Together, these data suggest evolutionary changes in the fms pathway or fms requirements, and identify changes in cellular interactions as a likely mechanism of evolutionary change in Danio pigment patterns.

Alleles↗

Diversification of gene function: homologs of the floral regulator FLO/LFY control the first zygotic cell division in the moss Physcomitrella patens.

After fertilization, the zygote undergoes dynamic changes in chromosomal and cytoplasmic organization, and begins the cell cycles that eventually lead to formation of the multicellular embryo. Specific transcription factors that initiate this cascade of events in land plants have not been identified. We have identified two FLO/LFY genes, PpLFY1 and PpLFY2, that regulate the first cell division after formation of the zygote in the moss Physcomitrella patens. The deduced amino acid sequences of the two PpLFY genes are 94.8% identical to each other and show similar expression patterns. While fertilization occurred in the PpLFY disruptants, the development of double disruptant zygotes was arrested at the single-cell stage. When the double disruptants, as the female parent, were crossed with the wild type, as the male parent, normal sporophytes were formed, supporting the notion that the PpLFY genes function after fertilization to regulate the first mitotic cell division in zygotes. The rare sporophytes that formed on the PpLFY double disruptants showed mostly normal organogenesis, but had abnormalities in the pattern of cell division, supporting a role of PpLFY genes in regulating cell division. The FLO/LFY genes in angiosperms are conserved master regulators of floral identity without any obvious effects on cell division. By contrast, our study suggests that FLO/LFY genes have functions throughout sporophyte development in the basal land plant lineages.

Arabidopsis↗

Anterior-posterior subdivision and the diversification of the mesoderm in Drosophila.

We have used a novel cell marker, in which the twist promoter directs the synthesis of the cell surface protein CD2 (twi-CD2) to examine the development of the mesoderm in the Drosophila embryo after gastrulation and to locate the progenitor cell populations for different mesodermal derivatives. We find that the early mesoderm in each segment is divided into a more anterior region with relatively low levels of twist and twi-CD2 expression and a more posterior region where twist and twi-CD2 expression are high. This subdivision coincides with regional assignments of cells to form different progenitors: dorsal anterior cells invaginate to form an internal layer from which the visceral mesoderm is derived. Ventral anterior cells form progenitors of mesodermal glial cells. Dorsal posterior cells form heart. Ventral and dorsal posterior cells form somatic muscles. We conclude that the metamerically repeated anterior-posterior subdivision of the mesoderm is an essential element in laying out the pattern of mesodermal progenitor cells and in distinguishing between an internal cell layer which will give rise to the progenitors of visceral muscles and an external layer which will generate the somatic muscles and the heart.

Animals↗

Terminal diversification of the myocyte lineage generates Purkinje fibers of the cardiac conduction system.

The rhythmic contraction of the vertebrate heart is dependent on organized propagation of electrical excitation through the cardiac conduction system. Because both muscle- and neuron-specific genes are co-expressed in cells forming myocardial conduction tissues, two origins, myogenic and neural, have been suggested for this specialized tissue. Using replication-defective retroviruses, encoding recombinant beta-galactosidase (beta-gal), we have analyzed cell lineage for Purkinje fibers (i.e., the peripheral elements of the conduction system) in the chick heart. Functioning myocyte progenitors were virally tagged at embryonic day 3 of incubation (E3). Clonal beta-gal+ populations of cells, derived from myocytes infected at E3 were examined at 14 (E14) and 18 (E18) days of embryonic incubation. Here, we report that a subset of clonally related myocytes differentiates into conductile Purkinje fibers, invariably in close spatial association with forming coronary arterial blood vessels. These beta-gal+ myogenic clones, containing both working myocytes and Purkinje fibers, did not incorporate cells contributing to tissues of the central conduction system (e.g. atrioventricular ring and bundles). In quantitative analyses, we found that whereas the number of beta-gal+ myocyte nuclei per clone more than doubled between E14 and E18, the number of beta-gal+ Purkinje fiber nuclei remained constant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Phylogenetic analyses of Zostera species based on rbcL and matK nucleotide sequences: implications for the origin and diversification of seagrasses in Japanese waters.

Seagrasses are composed of four families belonging to angiosperms and they are thought to become adaptive to aquatic life independently. Zosteraceae is one such family and because of the relatively high species diversity around Japan and Korea coast areas, the family might have arisen therefrom. To elucidate the origin and evolution of Zosteraceae which consists of three genera, Phyllospadix, Zostera, and Heterozostera, 2.8 kb nucleotide sequences of rbcL and matK genes in the chloroplast genome were examined for various species, including cosmopolitan Z. marina and endemic Z. caulescens. The phylogenetic analysis reveals the following three features. First, based on the synonymous nucleotide substitution rate of the rice chloroplast genome, we estimated the divergence times between Zosteraceae and its closest relative, Potamogetonaceae, and between different genera, Zostera and Phyllospadix, as approximately 100 million years (myr) and 36 myr, respectively, suggesting that Zosteraceae emerged somewhere in the period from 36 myr ago to 100 myr ago. Second, two subgenera of Zostera, Zostera and Zosterella, exhibit their reciprocal monophyly and appear to have differentiated from each other approximately 33 myr ago. However, the third genus Heterozostera branched off only 5 myr ago from the stem lineage leading to Zosterella and this seems too recent in comparison with the ancient divergence of the two subgenera. Third, we estimated the most recent common ancestor of subgenus Zostera as 6 myr. In Z. marina four haplotypes were found in the sample and have diversified in the past 1.5 myr. One haplotype is shared by both sides of the Japan Archipelago and its closely related haplotypes occur also in eastern Pacific Ocean. Based on these phylogeographic analyses, we propose a provisional age related classification of Zosteraceae to argue the origin and evolution.

Base Sequence↗

Diversification of the rice Waxy gene by insertion of mobile DNA elements into introns.

The waxy (wx) gene of Oryza glaberrima was cloned, and its nucleotide sequence was determined. A waxy mutant of O. glaberrima showing a glutinous phenotype was found to contain a substitution mutation generating a termination codon in the coding region of the wx gene. The Wx sequence of O. glaberrima was different from that of Oryza sativa by substitutions and insertions/deletions, among which only a few substitutions occurred in several exons not to severely alter the amino acid sequence of the Wx protein. The most striking difference observed in introns was a 139-bp deletion (or insertion) in intron 10 of O. glaberrima (or O. sativa). In O. sativa, 125 bp of the 139-bp sequence was flanked by direct repeats of a 14-bp sequence. A sequence homologous to the 125-bp sequence was found in the region preceding exon 2; this sequence was also flanked by direct repeats of another 14-bp sequence. This result and the observation that the 125-bp sequence was interspersed in rice genomes indicate that they are SINEs (short interspersed elements) in the plant system. We also identified a DNA sequence with long terminal inverted repeats in intron 13 of both O. glaberrima and O. sativa. This sequence was present in multiple copies in rice genomes, suggesting that it is a transposable element. These results obtained suggest that mobile DNA elements have diversified the rice Waxy gene by inserting into introns, each of which may originally have a length of about 100 bp.

Amino Acid Sequence↗

Polymorphic distribution and molecular diversification of mitochondrial plasmid-like DNAs in the genus Oryza.

Four kinds of circular plasmid-like DNA, designated B1, B2, B3 and B4, have been found in the mitochondria of rice (Oryza sativa L.). We analyzed the distribution of families of plasmid-like DNAs homologous to those of O. sativa in 40 strains of the genus Oryza with AA, BB, BBCC, CC, CCDD and EE genomes. Plasmid-like DNAs were observed only strains having AA, CC and CCDD genomes. The distribution patterns of strains with AA genome were highly polymorphic. We amplified the plasmid-like DNAs from strains with the AA genome by PCR and examined restriction fragments length polymorphisms (RFLPs). RFLPs were detected among families of plasmid-like DNA amplified from different strains. This result indicated that some mutations, such as base substitutions and the insertion or deletion of a small fragment of DNA, had occurred and had accumulated during the differentiation of strains with an AA genome.

Base Sequence↗