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Isolation of large numbers of chromosome 3-specific cosmids containing clusters of rare restriction-endonuclease sites.

We tested 519 chromosome 3-specific cosmids for the presence of rare restriction-endonuclease sites in a search for cosmids containing HTF islands. We have identified 49 cosmids (9% of those tested) that contain multiple rare restriction-endonuclease sites. The cosmids were digested with several common cutting restriction endonucleases to liberate small fragments which were tested as unique-sequence chromosome 3-specific hybridization probes and for evolutionary sequence conservation. Unique-sequence hybridization probes isolated from the cosmids were hybridized to a somatic cell hybrid deletion mapping panel to subchromosomally localize the cosmids. Fragments from many of these cosmids demonstrated conservation of sequence through evolution, and these fragments hybridize to distinct transcripts. These cosmids should therefore prove a useful resource for the identification of many chromosome 3-specific genes, in addition to having potential use as linking clones for pulsed-field gel mapping studies.

Biological Evolution↗

Variable heavy-chain gene analysis of follicular lymphomas: subclone selection rather than clonal evolution over time.

To investigate B-cell receptor evolution in follicular lymphomas (FLs), immunoglobulin variable heavy chain (V(H)) gene regions of 3 FLs were analyzed at different time points. One FL with a high somatic mutation load and intraclonal V(H) gene diversity was investigated in situ. V(H) gene transcripts were amplified and sequenced from samples of approximately 50 tumor cells isolated from frozen tissue sections by laser microdissection. Interestingly, the mutation pattern of the prevalent subclone in the relapse biopsy was virtually identical to that of a subclone isolated by microdissection from the presentation biopsy 9 years earlier. In a second FL, proof was obtained that the subclone that dominated the relapse sample had already been present in the initial biopsy. The finding that subclones found in the relapses of these FLs had not evolved over time but were preexistent, challenges the concept of antigen-driven B-cell receptor evolution during disease course.

Cell Transformation, Neoplastic↗

The other chromatin.

Current understanding of heterochromatin, thanks to molecular data, focuses on its performing several functions in evolution and development. Heterochromatin shows characteristic distribution patterns in karyotypes and contributes to the broad scattering of genome sizes through biological taxa. Heterochromatin remains compacted and thus different from properly stained euchromatin during somatic interphase. A minimum amount of heterochromatin, however, is required for it to be visible in light microscopy. It may further escape notice during the dynamic processes of embryogenesis and gametogenesis. Present-day biology is in search of specific proteins and DNA sequences that comprise heterochromatin. The data that result from overcoming the threshold of visibility will support understanding of interference by heterochromatin in ontogeny and evolution. The contributions of Sigrid and Wolfgang Beermann to the study of heterochromation diminution (DNA elimination) are recalled, and we also discuss the functions and effects of heterochromatin on differential DNA endoreplication and in speciation.

Animals↗

Invertebrates versus vertebrates innate immunity: In the light of evolution.

Invertebrates use a nonadaptive, innate immunity, the expression of germline encoded receptors, to identify the allogeneic and xenogeneic attributes. Vertebrates also have the capacity to express ontogenically related adaptive immunity which is a somatically selected gene rearrangement process. Several commonly accepted generalizations are utilized to explain the enigmatic lack of the adaptive immunity in invertebrates. All point to the primitive nature of the innate immunity and the primitive organization of the body plan and the life history patterns of invertebrates. Seven of the most common generalizations are reviewed and confuted by virtue of a biased literature presentation. Subsequently, three evolutionary puzzles are raised and the accepted paradigm that the vertebrate immunity is pathogenically directed is further challenged. This leads to an alternative idea suggesting that preserving the individuality against the threat of invading conspecific cells might have been the original function of the immune system. This ancient system has been co-opted later on to serve as a defence mechanism against pathogens. The secondary role arose in the form of a multiplicity of newly developed phenomena, one of them being the vertebrate adaptive immunity. This proposal is supported by the fact that vertebrates still exhibit two distinct but common types of naturally occurring transplantation events (natural chimerism) and by a variety of recent studies, providing evidence for the crucial role of the vertebrate's innate immunity in signalling and triggering the acquired effector mechanisms.

Adaptation, Physiological↗

X-chromosome inactivation and evolution in marsupials and other mammals.

Sex chromosome dosage compensation in Australian marsupials exhibits several characteristics not ordinarily manifested in eutherian mammals. They are: 1) preferential inactivation of the paternally derived X-chromosome in somatic tissues; 2) a state of partial inactivity at some paternally derived X-linked gene loci in some cells; 3) absence of dosage compensation in some cell types; 4) absence of nuclear sex dimorphism at interphase; 5) discordance between late DNA replication and gene inactivation in some cell types; 6) failure of the X-chromosome to behave as a single unit. Despite these seemingly major differences between the dosage compensation systems of Australian marsupials and eutherians, there are also many underlying similarities. We propose that the two systems arose from a common ancestral mechanism in which the X-chromosome was regulated in a piecemeal fashion, rather than as a whole. To determine more precisely the sequence and timing of evolutionary events, we have initiated an investigation of dosage compensation in American marsupials, which diverged from Australian marsupials soon after the divergence of marsupials from eutherian mammals.

Animals↗

Physiological adaptations and the concepts of optimal reproductive strategy and physiological constraint in marine invertebrates.

The dominant 'demographic' theory of life history evolution supposes that different lifetime patterns of reproduction are the result of selection of alternative optimal solutions for the allocation of limited resources between somatic and reproductive functions. A number of trade-off possibilities have been recognized--those between current reproductive output and residual reproductive value and between fecundity and initial offspring size being considered especially important. Many theoretical studies assume that natural selection will favour the adoption of optimal solutions, but it has been pointed out that such solutions may not be obtainable due to design constraints and the development of physiological adaptations to specific reproductive traits which limit subsequent evolutionary potential. The validity of this idea is examined in this paper through a review of the major reproductive strategies available to marine invertebrates and the physiological adaptations associated with them. The ecologically important distinction between planktotrophic and lecithotrophic development is not necessarily associated with major physiological adaptations in the adults, but the distinction between strictly semelparous and iteroparous life histories is. This is demonstrated in a survey of the endocrinological and environmental control of reproductive processes in related organisms with contrasting modes or reproduction. Particular reference is made to the Polychaeta, in which the contrast between semelparous and iteroparous life histories is particularly marked. A similar contrast is found between cephalopoda and other mollusca, and the discussion of physiological adaptations is extended to include these groups and the Echinodermata.

Adaptation, Physiological↗

Immunoglobulin differentiation is dictated by repeated recombination sequences within the V region prototype gene: a hypothesis.

Analysis of the available DNA sequences of immunoglobulin light chain genes reveals a unique structural pattern. A stretch of about 15 nucleotides repeats five times within the variable (V) region gene, with few base changes. Identification of these homologous sequences is apparent in the embryonic V(lambda) gene and might also be recognized in V(kappa) genes isolated from a myeloma. Although different from each other, the V(lambda) and V(kappa) hyperhomologous sequences display a remarkable resemblance to different prokaryote sequences associated with recombinational events. The homologous sequences appear at all three sites where hypervariable regions of the mature peptide are encoded. In addition, they are located at the site where V/constant (C) recombination is supposed to take place. Consequently, a general model is proposed for immunoglobulin differentiation. The hyperhomologous loci are postulated to be comprised of recombination sequences which makes them available for a mechanism of single-stranded DNA exposure. B cell maturation begins with V/C recombination, a step that is rate limiting. The fidelity of the process is ensured by extensive DNA homology between the two embryonic subgenes of V and C. Next, an error-prone repair system is activated and thereby introduces changes into the content of the immunoglobulin gene at the exposed loci. The process ends when mutations make the recombination sequence unrecognizable as such. The model is consistent with large amounts of data and is compatible with the view that immunoglobulin diversity is being generated somatically.

Animals↗

[Evolutionary regularities of the appearance of polyploidy in salivary glands of gastropod mollusks. III. A subclass of Pectinibranchia: Orders Discopoda, Echinospirida, Aspidophora and Entomostoma (Mesogastropoda)].

By means of histological methods and DNA cytophotometry, a study was made of the salivary glands of 16 species of gastropod molluscs belonging to the subclass Pectinibranchia and making a group of Mesogastropoda. Four cell types of salivary glands were distinguished: granular cells (with glycoproteid granular inclusions), mucocytes-I (with sulfatic acid mucopolysaccharides), mucocytes-II (with neutral and acid polysaccharides and proteins), and also the epithelial ciliated cells and mucous duct cells. Data of experiments on starvation and synchronous feeding of molluscs have testified that all described cell types are independent. In some species differentiation on protein and mucous departments within the glandular epithelium was shown. In some marine representatives of the orders Discopoda and Aspidophora polyploid cells with the ploidy levels from 8c to 32c were revealed along with diploid cells. The ecological and phylogenetic regularities of somatic polyploidy manifestation in Mesogastropoda are discussed.

Animals↗

Cell biology, molecular embryology, Lamarckian and Darwinian selection as evolvability.

The evolvability of vertebrate systems involves various mechanisms that eventually generate cooperative and nonlethal functional variation on which Darwinian selection can operate. It is a truism that to get vertebrate animals to develop a coherent machine they first had to inherit the right multicellular ontogeny. The ontogeny of a metazoan involves cell lineages that progressively deny their own capacity for increase and for totipotency in benefit of the collective interest of the individual. To achieve such cell altruism Darwinian dynamics rescinded its original unicellular mandate to reproduce. The distinction between heritability at the level of the cell lineage and at the level of the individual is crucial. However, its implications have seldom been explored in depth. While all out reproduction is the Darwinian measure of success among unicellular organisms, a high replication rate of cell lineages within the organism may be deleterious to the individual as a functional unit. If a harmoniously functioning unit is to evolve, mechanisms must have evolved whereby variants that increase their own replication rate by failing to accept their own somatic duties are controlled. For questions involving organelle origins, see Godelle and Reboud, 1995 and Hoekstra, 1990. In other words, modifiers of conflict that control cell lineages with conflicting genes and new mutant replication rates that deviate from their somatic duties had to evolve. Our thesis is that selection at the level of the (multicellular) individual must have opposed selection at the level of the cell lineage. The metazoan embryo is not immune to this conflict especially with the evolution of set-aside cells and other modes of self-policing modifiers (Blackstone and Ellison, 1998; Ransick et al., 1996. In fact, the conflict between the two selection processes permitted a Lamarckian soma-to-germline feedback loop. This new element in metazoan ontogeny became the evolvability of the vertebrate adaptive immune system and life as we know it now. We offer the hypothesis that metazoan evolution solved this ancient conflict by evolving an immunogenetic mechanism that responds with rapid Lamarckian efficiency by retaining the ancient reverse transcriptase enzyme (RNACopyright DNA copying discovered by Temin in 1959 (see Temin, 1989) and found in 1970 in RNA tumor viruses by Temin and Baltimore), which can produce cDNA from the genome of an RNA virus that infects the cells. It seems that molecular Lamarckism can survive (Lewin, 1993).

Allergy and Immunology↗

Evolution by DNA turnover in the control region of vertebrate mitochondrial DNA.

The control region of animal mitochondrial DNA is heterogeneous, including both highly conserved and highly variable sequences. Within the variable regions, variable number tandem repeat sequences have been described for numerous species. Repeats at one location, just upstream of the origin of replication, show an unprecedented level of length variation in somatic tissue. Recent comparison of these sequences in different species indicates a pattern of DNA turnover acting at different rates and over motifs of various sizes.

Animals↗

Gene dosage compensation and the evolution of sex chromosomes.

Dosage compensation is a mechanism by means of which the activity of X-linked or Z-linked genes is made equal in the two sexes of organisms with an XX compared to XY or ZZ compared to ZW basis of sex determination. In mammals, compensation is achieved by the inactivation of one X chromosome in somatic cells of females. In Drosophila, compensation does not involve inactivation. The two X chromosomes in females as well as the single X in males are regulated, and individual genes are thought to respond independently to the regulatory mechanism. It is proposed that in both groups of organisms the evolution of heteromorphic sex chromosomes was gradual and occurred as the direct result of the evolution of dosage compensation rather than the reverse.

Alleles↗

The march of symptoms in a psychotic decompensation. Case report and theoretical implications.

The onset and evolution of symptoms were studied in a female patient with a history of recurrent depressive psychoses. In each episode, her psychotic decompensations were characterized by an orderly and progressive sequence including similar psychological or somatic precipitants, mounting anxiety, nystagmoid eye movements associated with panic, unfolding delusions, and olfactory hallucinations, culminating in a complete psychotic regression. The evolving sequence repeated during each episode in the present case is compared with that of a similarly stereotyped progression of symptoms in temporal lobe and Jacksonian seizures. Kindling is suggested as a model relevant to the understanding of both epilepsy and the functional psychoses. Detailed observation of the evolution of symptoms during psychotic episodes may provide important clues to the underlying pathological anatomy and physiology of psychotic illness.

Adolescent↗

Variable domains and a VpreB-like molecule are present in a jawless vertebrate.

Immunoglobulins (Igs) and T cell antigen receptors (TCRs) that undergo somatic diversification have not been identified in the two extant orders of jawless vertebrates, which occupy essential positions in terms of understanding the evolution of the emergence of adaptive immunity. Using a single motif-dependent PCR-based approach coupled with a vector that allows selection of cDNAs encoding secretion signal sequences, four different genes encoding Ig V-type domains were identified in the sea lamprey (Petromyzon marinus). One of the predicted proteins encoded by these genes shares structural characteristics with mammalian VpreB molecules, including the absence of a recognizable transmembrane region, a relatively high proportion of charged amino acids in its C-terminal tail and distinctive features of its secretion signal peptide. This is the first indication of a molecule related to the B cell receptor (BCR) complex in a species that diverged prior to the jawed vertebrates in which RAG-mediated adaptive immunity is first encountered.

Amino Acid Sequence↗

Identification of five different insulin-like growth factor binding proteins (IGFBPs) from adult rat serum and molecular cloning of a novel IGFBP-5 in rat and human.

Five different insulin-like growth factor binding proteins (IGFBPs) were isolated from adult rat serum using gel filtration, ligand affinity chromatography, and two steps of reversed-phase high performance liquid chromatography. Three of them were identified as IGFBP-2, -3, and -4 by their amino-terminal amino acid sequences. One of the remaining two proteins was the rat homologue of the partially characterized IGFBP isolated originally from human cerebrospinal fluid, while the other appeared to be a novel member of the IGFBP family. IGFBP-1 was not found in the adult rat serum under our experimental procedures. cDNAs encoding the novel IGFBP were isolated and characterized from a rat ovary and a human placenta library. The mature protein predicted for both species contained 252 amino acids including 18 cysteines that were located in the homologous positions as IGFBP-1, -2, -3, and -4. We propose to name this protein IGFBP-5. Northern analysis of IGFBP-5 mRNA in rat tissues demonstrated that transcription of this gene is highly active in kidney, although the mRNA was detectable in all tissues examined. Alignment of the amino acid sequences of the five rat IGFBPs revealed a 47-60% similarity, indicating that their individual genes diverged from a single ancestral gene by successive gene duplication in a short time frame during evolution. The chromosomal localizations of IGFBP-1, -2, -3, -4, and -5 genes in human have been determined using polymerase chain reaction on somatic cell hybrid DNAs of human and hamster, and the results showed that they were located on chromosomes 7, 2, 7, 17, and 5, respectively.

Amino Acid Sequence↗

Evolution of longevity in mammals.

Maximum life span is a characteristic of each species, and a diversity of maximum species life spans is seen in each mammalian order. It is argued here that different clusters of related long-lived species evolved independently. A variety of genes could have been involved such as genes for somatic maintenance and genes for resistance to causes of death, including fatal diseases. There are explanations based on natural selection for the long maximum human life span, half of which is post-reproductive.

Animals↗

Clinical transformation of chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is usually stable over months to years however a small proportion of cases may transform to more aggressive forms. These transformations include diffuse lymphoma (Richter syndrome), prolymphocytic transformation, acute lymphoblastic leukemia and multiple myeloma. There are a variety of techniques to determine whether the transformation represents a clonal evolution of the original CLL or an independent disease. These include cytogenetic analysis, immunoglobulin gene rearrangement by Southern blot analysis, and anti-idiotypic antibodies. While identity can be determined by gene rearrangement and anti-idiotypic antibodies, lack of identity can occur because of somatic mutation within a single clone. Thus, even with optimal techniques it is difficult to definitively exclude lack of identity in some instances. In most cases where transformation has taken place, definitive studies were not performed. In instances where detailed data are available, most do not suggest clonal evolution. Further studies are needed to allow definite conclusions.

Cell Transformation, Neoplastic↗

[Organization and evolution of animal colonies].

Based on the theory of organization and evolution of colonies in an extinct group of hemichordates graptolites (Urbanek, 1960, 1973) the relationship between the events in the late astogeny of bryozoan colonies and their somatic and reproductive cycle. The bryozoan colonies with simple organization are compared with graptoloid colonies and their structure is interpreted within the framework of the morphogen gradient theory. A morphogen produced by the founder-zooid (oozooid) diffuses along the long axis of the colonies and regulates the phenotypic expression of the size and structure of zooids. Evolutionary changes in the graptoloid colonies involve introduction of new characters and their spreading is also accompanied by gradient changes of their manifestation. Evolutionary mechanisms in bryozoan colonies are considered in terms of penetrance and expressivity of genes. In contrast to graptolites, many bryozoan colonies display multiple zones of astogeny changes and repetitions.

Animals↗