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Isologous diversification: a theory of cell differentiation.

An isologous diversification theory for cell differentiation is processed, based on simulations of interacting cells with biochemical networks and the cell division process following consumption of some chemicals. According to the simulations of the interaction-based dynamical systems model, the following scenario of the cell differentiation is proposed. (1) Up to some threshold number, divisions bring about almost identical cells with synchronized biochemical oscillations. (2) As the number is increased, the oscillations lose synchrony, leading to groups of cells with different phases of oscillations. (3) Amplitudes of oscillation and averaged chemical compositions start to differ by groups of cells. The differentiated behavior of states is transmitted to daughter cells. (4) Recursivity is formed so that the daughter cells keep the identical chemical character. This "memory" is made possible through the transfer of initial conditions. (5) Successive differentiation proceeds. The mechanism of tumor cell formation, origin of stem cells, anomalous differentiation by transplantations, apoptosis and other features of cell differentiation process are also discussed, with some novel predictions.

Animals↗

Rapid diversification of marine picophytoplankton with dissimilar light-harvesting structures inferred from sequences of Prochlorococcus and Synechococcus (Cyanobacteria).

Cultured isolates of the unicellular planktonic cyanobacteria Prochlorococcus and marine Synechococcus belong to a single marine picophytoplankton clade. Within this clade, two deeply branching lineages of Prochlorococcus, two lineages of marine A Synechococcus and one lineage of marine B Synechococcus exhibit closely spaced divergence points with low bootstrap support. This pattern is consistent with a near-simultaneous diversification of marine lineages with divinyl chlorophyll b and phycobilisomes as photosynthetic antennae. Inferences from 16S ribosomal RNA sequences including data for 18 marine picophytoplankton clade members were congruent with results of psbB and petB and D sequence analyses focusing on five strains of Prochlorococcus and one strain of marine A Synechococcus. Third codon position and intergenic region nucleotide frequencies vary widely among members of the marine picophytoplankton group, suggesting that substitution biases differ among the lineages. Nonetheless, standard phylogenetic methods and newer algorithms insensitive to such biases did not recover different branching patterns within the group, and failed to cluster Prochlorococcus with chloroplasts or other chlorophyll b-containing prokaryotes. Prochlorococcus isolated from surface waters of stratified, oligotrophic ocean provinces predominate in a lineage exhibiting low G + C nucleotide frequencies at highly variable positions.

Animals↗

Largest bird from the Early Cretaceous and its implications for the earliest avian ecological diversification.

With only one known exception, early Cretaceous birds were smaller than their closest theropod dinosaur relatives. Here we report on a new bird from the Early Cretaceous feathered-dinosaur-bearing continental deposits of Liaoning, northeast China, which is not only larger than Archaeopteryx but is nearly twice as large as the basal dromaeosaur Microraptor. The new taxon, Sapeornis chaoyangensis gen. et sp. nov., has a more basal phylogenetic position than all other birds except for Archaeopteryx. Its exceptionally long forelimbs, well-developed deltoid crest of the humerus, proximally fused metacarpals, relatively short hindlimbs and short pygo-style indicate powerful soaring capability and further suggest that by the Early Cretaceous ecological diversification of early birds was greater than previously assumed. Electronic supplementary material to this paper can be obtained by using the Springer LINK server located at http://dx.doi.org/10.1007/s00114-001-0276-9.

Animals↗

Diversification and independent evolution of troponin C genes in insects.

Troponin C (TpnC), the calcium-binding subunit of the troponin regulatory complex in the muscle thin filament, is encoded by multiple genes in insects. To understand how TpnC genes have evolved, we characterized the gene number and structure in a number of insect species. The TpnC gene complement is five genes in Drosophilidae as previously reported for D. melanogaster. Gene structures are almost identical in D. pseudoobscura, D. suboboscura, and D. virilis. Developmental patterns of expression are also conserved in Drosophila subobscura and D. virilis. Similar, but not completely equivalent, TpnC gene repertoires have been identified in the Anopheles gambiae and Apis mellifera genomes. Insect TpnC sequences can be divided into three groups, allowing a systematic classification of newly identified genes. The pattern of expression of the Apis mellifera genes essentially agrees with the pattern in Drosophilidae, providing further functional support to the classification. A model for the evolution of the TpnC genes is proposed including the most likely pathway of insect TpnC diversification. Our results suggest that the rapid increase in number and sequence specialization of the adult Type III isoforms can be correlated with the evolution of the holometabolous mode of development and the acquisition of asynchronous indirect flight muscle function in insects. This evolutionarily specialization has probably been achieved independently in different insect orders.

Amino Acid Sequence↗

Adaptive diversification of vomeronasal receptor 1 genes in rodents.

The vomeronasal receptor 1 (V1R) are believed to be pheromone receptors in rodents. Here we used computational methods to identify 95 and 62 new putative V1R genes from the draft rat and mouse genome sequence, respectively. The rat V1R repertoire consists of 11 subfamilies, 10 of which are shared with the mouse, while rat appears to lack the H and I subfamilies found in mouse and possesses one unique subfamily (M). The estimations of the relative divergence times suggest that many subfamilies originated after the split of rodents and primates. The analysis also reveals that these clusters underwent an expansion very close to the split of mouse and rat. In addition, maximum likelihood analysis showed that the nonsynonymous and synonymous rate ratio for most of these clusters was much higher than one, suggesting the role of positive selection in the diversification of these duplicated V1R genes. Because V1R are thought to mediate the process of signal transduction in response to pheromone detection, we speculate that the V1R genes have evolved under positive Darwinian selection to maintain the ability to discriminate between large and complex pheromonal mixtures.

Adaptation, Physiological↗

Inter- and intralocus recombination drive MHC class IIB gene diversification in a teleost, the three-spined stickleback Gasterosteus aculeatus.

The mutational mechanism underlying the striking diversity in MHC (major histocompatibility complex) genes in vertebrates is still controversial. In order to evaluate the role of inter- and intragenic recombination in MHC gene diversification, we examined patterns of nucleotide polymorphism across an exon/intron boundary in a sample of 31 MHC class IIB sequences of three-spined stickleback (Gasterosteus aculeatus). MHC class IIB genes of G. aculeatus were previously shown to be under diversifying (positive) selection in mate choice and pathogen selection experiments. Based on recoding of alignment gaps, complete intron 2 sequences were grouped into three clusters using maximum-parsimony analysis. Two of these groups had >90% bootstrap support and were tentatively assigned single locus status. Intron nucleotide diversity within and among loci was low (p-distance within and among groups = 0.016 and 0.019, respectively) and fourfold lower than the rate of silent mutations in exon 2, suggesting that noncoding regions are homogenized by frequent interlocus recombination. A substitution analysis using GENECONV: revealed as many intergenic conversion events as intragenic ones. Recombination between loci may explain the occurrence of sequence variants that are particularly divergent, as is the case in three-spined stickleback, with nucleotide diversity attaining dN = 0.39 (peptide-binding residues only). For both MHC class II loci we also estimated the amount of intragenic recombination as population rate (4N(e)r) under the coalescent and found it to be approximately three times higher compared to point mutations (Watterson estimate per gene, 4N(e)mu). Nonindependence of molecular evolution across loci and frequent recombination suggest that MHC class II genes of bony fish may follow different evolutionary dynamics than those of mammals. Our finding of widespread recombination suggests that phylogenies of MHC genes should not be based on coding segments but rather on noncoding introns.

Animals↗

New aspects on lanosterol 14alpha-demethylase and cytochrome P450 evolution: lanosterol/cycloartenol diversification and lateral transfer.

Sterol 14alpha-demethylase (CYP51) is a member of the cytochrome P450 superfamily, widely found in animals, fungi, and plants but present in few prokaryotic groups. CYP51 is currently believed to be the ancestral cytochrome P450 that has been transferred from prokaryotes to eukaryotic kingdoms. We propose an alternate view of CYP51 evolution that has an impact on understanding the evolution of the entire CYP superfamily. Two hundred forty-nine bacterial and four archaeal CYP sequences have been aligned and a bacterial CYP tree designed, showing a separation of two branches. Prokaryotic CYP51s cluster to the minor branch, together with other eukaryote-like CYPs. Mycobacterial and methylococcal CYP51s cluster together (100% bootstrap probability), while Streptomyces CYP51 remains on a distant branch. A CYP51 phylogenetic tree has been constructed from 44 sequences resulting in a ((plant, bacteria),(animal, fungi)) topology (100% bootstrap probability). This is in accordance with the lanosterol/cycloartenol diversification of sterol biosynthesis. The lanosterol branch (nonphotosynthetic lineage) follows the previously proposed topology of animal and fungal orthologues (100% bootstrap probability), while plant and D. discoideum CYP51s belong to the cycloartenol branch (photosynthetic lineage), all in accordance with biochemical data. Bacterial CYP51s cluster within the cycloartenol branch (69% bootstrap probability), which is indicative of a lateral gene transfer of a plant CYP51 to the methylococcal/mycobacterial progenitor, suggesting further that bacterial CYP51s are not the oldest CYP genes. Lateral gene transfer is likely far more important than hitherto thought in the development of the diversified CYP superfamily. Consequently, bacterial CYPs may represent a mixture of genes with prokaryotic and eukaryotic origin.

Bacteria↗

Phylogenetic timing of the fish-specific genome duplication correlates with the diversification of teleost fish.

For many genes, ray-finned fish (Actinopterygii) have two paralogous copies, where only one ortholog is present in tetrapods. The discovery of an additional, almost-complete set of Hox clusters in teleosts (zebrafish, pufferfish, medaka, and cichlid) but not in basal actinopterygian lineages ( Polypterus) led to the formulation of the fish-specific genome duplication hypothesis. The phylogenetic timing of this genome duplication during the evolution of ray-finned fish is unknown, since only a few species of basal fish lineages have been investigated so far. In this study, three nuclear genes ( fzd8, sox11, tyrosinase) were sequenced from sturgeons (Acipenseriformes), gars (Semionotiformes), bony tongues (Osteoglossomorpha), and a tenpounder (Elopomorpha). For these three genes, two copies have been described previously teleosts (e.g., zebrafish, pufferfish), but only one orthologous copy is found in tetrapods. Individual gene trees for these three genes and a concatenated dataset support the hypothesis that the fish-specific genome duplication event took place after the split of the Acipenseriformes and the Semionotiformes from the lineage leading to teleost fish but before the divergence of Osteoglossiformes. If these three genes were duplicated during the proposed fish-specific genome duplication event, then this event separates the species-poor early-branching lineages from the species-rich teleost lineage. The additional number of genes resulting from this event might have facilitated the evolutionary radiation and the phenotypic diversification of the teleost fish.

Animals↗

Evolution and diversification of RNA silencing proteins in fungi.

Comprehensive phylogenetic analyses of fungal Argonaute, Dicer, and RNA-dependent RNA polymerase-like proteins have been performed to gain insights into the diversification of RNA silencing pathways during the evolution of fungi. A wide range of fungi including ascomycetes, basidiomycetyes, and zygomycetes possesses multiple RNA silencing components in the genome, whereas a portion of ascomycete and basidiomycete fungi apparently lacks the whole or most of the components. The number of paralogous silencing proteins in the genome differs considerably among fungal species, suggesting that RNA silencing pathways have diversified significantly during evolution in parallel with developing the complexity of life cycle or in response to environmental conditions. Interestingly, orthologous silencing proteins from different fungal clades are often clustered more closely than paralogous proteins in a fungus, indicating that duplication events occurred before speciation events. Therefore, the origin of multiple RNA silencing pathways seems to be very ancient, likely having occurred prior to the divergence of the major fungal lineages.

Ascomycota↗

Diversification of exogenous genes in vivo in Neurospora.

We have adapted the meiotic recombination hotspot cog of Neurospora crassa for shuffling exogenous DNA, providing a means of generating novel genes in situ from sequences introduced into chromosomes. Genes to be diversified are inserted between the his-3 locus and cog. Diversification crosses are heterozygous both for alleles of the exogenous DNA and for auxotrophic alleles of his-3. Progeny selected for ability to grow without histidine supplementation are enriched for exchange events within the exogenous DNA. Exchange events initiated by cog can propagate past DNA sequences mismatched for more than 370 bp and complete exchanges in patches of matched sequence as short as 24 bp, parameters that make the system suited for use in the directed evolution of genes for protein engineering. Here we demonstrate the system by shuffling human immunoglobulin kappa chain genes and also endoglucanase genes derived from different species of fungi.

Cellulase↗

Diversification of minimally invasive parathyroidectomy for primary hyperparathyroidism: minimally invasive video-assisted parathyroidectomy and minimally invasive open videoscopically magnified parathyroidectomy with local anesthesia.

With the expansion of minimally invasive parathyroid surgery for primary hyperparathyroidism, new approaches and techniques evolved, creating new surgical algorithms with consequences for indication for surgery and patient selection. The presented methods of selective, minimally invasive parathyroidectomy represent this development of diversification. Minimally invasive video-assisted parathyroidectomy (MIVAP) has advanced to bilateral exploration, avoiding preoperative localization other than ultrasonography. Furthermore, a new technique of minimally invasive open parathyroidectomy with the option of videoscopic magnification under local anesthesia (MIPLA) for localizable adenomas is introduced. A series of 103 patients were operated on for primary hyperparathyroidism using minimally invasive procedures: 87 with MIVAP and 16 with MIPLA. With MIVAP the conversion rate to cervicotomy for multiglandular disease or technical difficulties was 16% (n = 14). With MIPLA, conversion to general intubation anesthesia or additional sedation was necessary in four patients. A transient laryngeal nerve palsy was observed in one patient with MIVAP. Bilateral exploration was carried out during 29 MIVAPs and 2 MIPLAs. The duration of surgery differed, with a median 63 minutes for MIVAP and 39 minutes for MIPLA. Surgery under local anesthesia was completed in 4 patients with MIVAP and in 14 with MIPLA. All patients were cured of primary hyperparathyroidism. Preliminary results of diversified procedures demonstrate effects regarding omission of preoperative diagnostics, overall cost reduction, and increasing patient selection for selective parathyroid surgery because of primary hyperparathyroidism.

Adenoma↗

Diversification of hepatitis C viruses in South America reveals a novel genetic lineage.

Hepatitis C virus (HCV) has high genomic variability and, since its discovery, at least six different types and an increasing number of sub-types have been reported. Genotype 1 is the most prevalent genotype found in South America. Recent phylogenetic analysis of strains isolated in Uruguay revealed the presence of a different genetic lineage from major sub-types 1a and 1b. In order to study if type 1 HCV strains circulating in the South American region can be associated with this genetic lineage, sequence data obtained from the 5' non-coding region from 6 type 1 patients from Chile, were compared with sequences obtained from 12 type 1 Uruguayan and 9 type 1 Brazilian patients as well as 17 different strains of all types isolated elsewhere. The phylogenetic analysis revealed the existence of type 1 strains of this novel genetic lineage in all South American countries studied, and indicates a diversification of HCV viruses in the South American region.

5' Untranslated Regions↗

Molecular diversification in spider venoms: a web of combinatorial peptide libraries.

Spider venoms are a rich source of novel pharmacologically and agrochemically interesting compounds that have received increased attention from pharmacologists and biochemists in recent years. The application of technologies derived from genomics and proteomics have led to the discovery of the enormous molecular diversity of those venoms, which consist mainly of peptides and proteins. The molecular diversity of spider peptides has been revealed by mass spectrometry and appears to be based on a limited set of structural scaffolds. Genetic analysis has led to a further understanding of the molecular evolution mechanisms presiding over the generation of these combinatorial peptide libraries. Gene duplication and focal hypermutation, which has been described in cone snails, appear to be common mechanisms to venomous mollusks and spiders. Post-translational modifications, fine structural variations and new molecular scaffolds are other potential mechanisms of toxin diversification, leading to the pharmacologically complex cocktails used for predation and defense.

Amino Acid Sequence↗

Conservation and diversification of SCARECROW in maize.

The SCARECROW (SCR) gene in Arabidopsis is required for asymmetric cell divisions responsible for ground tissue formation in the root and shoot. Previously, we reported that Zea mays SCARECROW (ZmSCR) is the likely maize ortholog of SCR. Here we describe conserved and divergent aspects of ZmSCR. Its ability to complement the Arabidopsis scr mutant phenotype suggests conservation of function, yet its expression pattern during embryogenesis and in the shoot system indicates divergence. ZmSCR expression was detected early during embryogenesis and localized to the endodermal lineage in the root, showing a gradual regionalization of expression. Expression of ZmSCR appeared to be analogous to that of SCR during leaf formation. However, its absence from the maize shoot meristem and its early expression pattern during embryogenesis suggest a diversification of ZmSCR in the patterning processes in maize. To further investigate the evolutionary relationship of SCR and ZmSCR, we performed a phylogenetic analysis using Arabidopsis, rice and maize SCARECROW-LIKE genes (SCLs). We found SCL23 to be the most closely related to SCR in both eudicots and monocots, suggesting that a gene duplication resulting in SCR and SCL23 predates the divergence of dicots and monocots.

Arabidopsis↗

Development of T-cell function in relation to T-cell set diversification in nu/nu mice.

The differentiation pattern of splenic T-cell populations in germ- and pathogen-free nu/nu mice, as compared to nu/+ littermates, is characterized by two abnormal features: the expression of TL determinants on peripheral T cells and the delayed onset of their differentiation from the predominant Lyt-123:TL+ set into TL- cells of Lyt-1+ and Lyt-123+ phenotype, which, in these mice, does not occur until 10 weeks of age. We report here that the delayed onset of mitogen- or alloantigen-induced interleukin-2 synthesis and T-cell proliferation as well as the development of cytotoxic T-lymphocyte activity of enriched T-cell populations is strictly correlated with the time point of T-cell subset diversification in nu/nu mice and depends in particular on the presence of the Lyt-1 (TL-:Lyt-2-) T-cell set which is lacking in splenic T-cell populations of germ-free young nu/nu mice.

Age Factors↗

Two mechanisms of antigenic diversification of foot-and-mouth disease virus.

The amino acid replacements that underlay the diversification of the main antigenic site A (VP1 residues 138 to 150) of foot-and-mouth disease virus (FMDV) of serotype C have been identified. Sixteen new VP1 sequences of isolates from 1926 until 1989 belonging to subtypes C1, C2, C3, C4, C5, and unclassified are reported. The reactivities in enzyme-linked immunoelectrotransfer blot assays of capsid protein VP1 with a panel of neutralizing monoclonal antibodies that recognize sites A or C (the VP1 carboxy-terminus) have been correlated with the amino acid sequence at the relevant epitopes. The analyses involving the immunodominant site A reveal two mechanisms of antigenic change. One is a gradual increase in antigenic distance brought about by accumulation of amino acid replacements at two hypervariable segments within site A. A second mechanism consists of an abrupt antigenic change manifested by loss of many epitopes, caused by one replacement at a critical position (particularly Ala (145)----Val or His (146)----Gln). The identification of the amino acid substitutions responsible for such large antigenic changes provides new information for the design of synthetic anti-FMD vaccines. However, the screening of isolates from six decades suggests that the virus, even within the confines of a single serotype, has exploited a minimum of its potential for antigenic variation.

Amino Acid Sequence↗

Transporter associated with antigen-processing-1 (TAP1) alleles in Gorilla gorilla: diversification of the locus postspeciation.

The transporter associated with antigen-processing (TAP) proteins are required for the transport of cytosolic peptides into the endoplasmic reticulum for assembly with class I major histocompatibility molecules. In the rat, allelic variants of the TAP genes impart specificity to the process of peptide transport. However, differential transport has yet to be demonstrated with the human molecules. TAP genes from humans and rodents have been studied thus far; analysis of another species more closely related to humans is necessary for a clearer understanding of the evolution of TAP genes. Three TAP1 alleles from four gorilla cell lines were characterized in this study. There is limited genetic distance at the locus, either within the gorilla (0.2%) or between the two hominoid species (0.8%). Nucleotide substitution analysis demonstrates that TAP1 and TAP2 are evolving at comparable rates under similar selection pressures. This pattern is in marked contrast to that observed for MHC class I genes of hominoids or rodents. Although there is limited evidence for trans-species evolution of the gorilla locus, the bulk of the diversification occurred after speciation as evidenced by a lack of shared amino acid polymorphism with human homologues. An evolutionary scheme predicts that the ancestral hominoid TAP1 molecule most closely resembled the human TAP1*02011.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Cell and molecular biology of neural crest cell lineage diversification.

Neural crest cells are multipotent progenitor cells, but it is not understood how these cells generate their diverse differentiated progeny. This review considers the issues of whether neural crest cells self-renew, whether they generate partially committed intermediate progenitors, and how the local embryonic environment may act to control this diversification process. Novel molecular markers for neural crest cells are also discussed.

Animals↗