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Clonal and morphological variation in a posttransplant lymphoproliferative disorder: evolution from clonal T-cell to clonal B-cell predominance.

The majority of posttransplant lymphoproliferative disorders (PTLD) are Epstein-Barr virus (EBV)-associated and of B-cell origin. A much smaller proportion of PTLD are of T-cell origin. We report the clinical, morphological, immunophenotypic, and genotypic results of a unique PTLD, initially diagnosed as immune mediated thrombocytopenia (ITP), which at presentation was predominantly an anaplastic appearing EBV-associated T-cell PTLD and, after reduction in immunosuppression and the administration of antiviral agents, predominantly an EBV-associated plasma cell rich B-cell PTLD. Subsequent chemotherapy resulted in a complete remission. This case has both practical and biological implications. It highlights how PTLD may be misdiagnosed as other entities, how biclonal cases can have different morphological appearances and include both B- and T-cell clones, how PTLD can evolve over time possibly related to immune reconstitution, and why PTLD should be rebiopsied when the disease does not respond to decreased immunosuppression or recurs.

B-Lymphocytes↗

The structure of anchovy outer retinae (Engraulididae, Clupeiformes) - a comparative light- and electron-microscopic study using museum-stored material.

The outer retinal architecture of Engraulididae is uncommon among vertebrates. In some anchovies, e.g., Anchoa, two cone types are arranged alternating in long photoreceptor chains, i.e., polycones. The cones have radially oriented outer segment lamellae in close contact with a complex guanine tapetum, most probably subserving polarization contrast vision. To clarify the distribution of the aberrant polycone architecture within the Engraulididae and to provide indications about polycone evolution, the outer retina morphology of 16 clupeoid species was investigated by light and electron microscopy, predominantly using museum-stored material. The outgroup representatives of four clupeid subfamilies (Clupeonella cultriventris, Dorosoma cepedianum, Ethmalosa fimbriata, Pellonula leonensis) show a row pattern of double cones, partially with single cones at defined positions and a pigment epithelium with lobopodial protrusions containing melanin. The pristigasterid Ilisha africana has double rows of single cones lying between linear curtains of pigment epithelium processes filled with minute crystallites and melanin concentrated near their vitreal tips. Within the Engraulididae, two main architectures are found: Coilia nasus and Thryssa setirostris have linear multiple cones or polycones separated by long pigment epithelium barriers containing tapetal crystallites and melanin in the tips (also found in Setipinna taty), whereas Anchoviella alleni, Encrasicholina heteroloba, Engraulis encrasicolus, Engraulis mordax, Lycengraulis batesii, and Stolephorus indicus exhibit the typical polycone architecture. Cetengraulis mysticetus and Lycothrissa crocodilus show cone patterns and pigment epithelium morphology differing from the other anchovy species. The sets of characters are compared, corroborated with the previous knowledge on clupeoid retinae and discussed in terms of functional morphology and visual ecology. A scenario on polycone evolution is developed that may serve as an aid for the reconstruction of engraulidid phylogeny. Furthermore, this study demonstrates the suitability of museum material for morphological studies, even at the electron microscopic level.

Animals↗

A newly recognized fossil coelacanth highlights the early morphological diversification of the clade.

Previously considered an actinopterygian or an osteichthyan incertae sedis, the Devonian (Givetian-Frasnian) Holopterygius nudus is reinterpreted as a coelacanth. This genus is among the oldest coelacanths known from articulated remains, but its eel-like morphology marks a considerable departure from the conventional coelacanth body plan. A cladistic analysis places Holopterygius as the sister taxon of the Carboniferous (Serpukhovian) genus Allenypterus. Despite the specialized morphology of these genera, they occupy a surprisingly basal position in coelacanth phylogeny; only Diplocercides and Miguashaia are further removed from the crown. A morphometric analysis reveals that coelacanths were anatomically disparate early in their history. Conflicts between this result and those of previous studies challenge the adequacy of systematic character sets for describing historical patterns of morphological variety. Coelacanths have long had an iconic place in the study of vertebrate evolution for their apparent anatomical conservatism over geological time, but Holopterygius provides clear evidence for rapid morphological evolution early in the history of this clade.

Animals↗

Developmental studies of the lamprey and hierarchical evolutionary steps towards the acquisition of the jaw.

The evolution of animal morphology can be understood as a series of changes in developmental programs. Among vertebrates, some developmental stages are conserved across species, representing particular developmental constraints. One of the most conserved stages is the vertebrate pharyngula, in which similar embryonic morphology is observed and the Hox code is clearly expressed. The oral developmental program also appears to be constrained to some extent, as both its morphology and the the Hox-code-default state of the oropharyngeal region are well conserved between the lamprey and gnathostome embryos. These features do not by themselves explain the evolution of jaws, but should be regarded as a prerequisite for evolutionary diversification of the mandibular arch. By comparing the pharyngula morphology of the lamprey and gnathostomes, it has become clear that the oral pattern is not entirely identical; in particular, the positional differentiation of the rostral ectomesenchyme is shifted between these animals. Therefore, the jaw seems to have arisen as an evolutionary novelty by overriding ancestral constraints, a process in which morphological homologies are partially lost. This change involves the heterotopic shift of tissue interaction, which appears to have been preceded by the transition from monorhiny to diplorhiny, as well as separation of the hypophysis. When gene expression patterns are compared between the lamprey and gnathostomes, cell-autonomously functioning genes tend to be associated with identical cell types or equivalent anatomical domains, whereas growth-factor-encoding genes have changed their expression domains during evolution. Thus, the heterotopic evolution may be based on changes in the regulation of signalling-molecule-encoding genes.

Animals↗

Interstrain variations in nephritogenicity of heterologous protein in mice.

Swiss albino, BALB/c, and eight substrains of C3H mice were given daily intraperitoneal injections of horse apoferritin (HAF) for up to 56 days. At varying intervals, renal tissue was examined by light, immunofluorescence, and electron microscopy. Swiss mice developed proliferative glomerulonephritis after 7 to 14 days of HAF, and 45 per cent progressed to severe crescentic glomerulonephritis after from 21 to 56 days of HAF. In Swiss mice, glomerular immune deposits evolved from predominantly IgM mesangial deposits at 7 days to mesangial IgG at 14 days to capillary wall IgG after 21 or more days of HAF injections. BALB/c mice given identical HAF doses never developed severe crescentic glomerulonephritis but rather an extensive global necrotizing glomerulonephritis most prevalent after from 9 to 18 days of HAF. The distinct evolution of glomerular immune deposits observed in Swiss mice was less clear-cut in BALB/c mice, with greater persistence of mesangial deposits and IgM over time. Only 11 per cent of C3H mice (confined to two substrains) developed glomerular lesions by light microscopy after 2 to 3 weeks of HAF administration. No C3H/HeN mice developed glomerulonephritis even after up to 47 days of HAF injection. From 7 days on, 45 per cent of HAF-injected C3H mice had low level IgM mesangial immune deposits but did not manifest the evolution from mesangial to capillary deposition observed in BALB/c and Swiss albino mice. F1 hybrid and congenic mice carrying BALB/c H-2 genetic information developed glomerular lesions similar to those produced in BALB/c mice. These data (1) indicate an interrelated morphologic and immunohistologic evolution of heterologous protein induced glomerular lesions in mice, (2) demonstrate morphologic and immunohistologic differences in glomerular lesions development between genetically disparate mouse strains given identical antigen exposures, and (3) support the genetic control of heterologous protein-induced glomerulonephritis and suggest a role for the major histocompatibility region in this genetic regulation.

Animals↗

Constructional morphology and mode of attachment of the trunk of Corynosoma cetaceum (Acanthocephala: Polymorphidae).

Dead specimens of Corynosoma cetaceum were used to describe the trunk musculature of this species and to infer the use of the trunk as a secondary holdfast. Inferences were based on trunk muscle arrangement, changes in trunk shape, size and distribution of spines, and geometry of tegument thickness. The foretrunk of C. cetaceum is swollen and forms a spiny disk that is bent ventrally. The disk is flattened by several groups of muscles not described previously, which seem able to finely adjust the disk surface over the substratum. Disk attachment appears to be accomplished by two dorsal neck retractor muscles specialized in pulling the anchored proboscis into the foretrunk. This mechanism has been described in other acanthocephalans, becoming surprisingly efficient when used with a flattened, armed foretrunk. The ventrally spined hindtrunk requires force to move downwards in order to attach. A single ventral neck retractor muscle seems specialized in pulling the posterior trunk forward, inducing a downward force due to the muscle's precise points of insertion. This mechanism necessarily generates ventral wrinkling that needs to be eliminated for the spiny surface to be functional. The trunk ventral muscles are apparently arranged so as to concentrate the "excess" of the tegument into a single fold, optimizing the use of the remaining surface for attachment. The size and distribution of spines, as well as the geometry of tegumental thickness, conform to these observations. Morphological changes, seemingly simple, such as structural bending, may have triggered a cascade of subtle modifications and new functions during acanthocephalan evolution, reflecting how morphological integration and novelty interact.

Acanthocephala↗

The scale independence of evolution.

In this paper, I argue that the ultimate causes of morphological, and hence developmental, evolution are scale independent. In other words, micro- and macroevolutionary patterns show fundamental similarities and therefore are most simply explained as being caused by the same kinds of evolutionary forces. I begin by examining the evolution of single lineages and argue that dynamics of adaptive evolution are the same for bacteria in test-tube evolution experiments and fossil lineages. Similarly, I argue that the essential features of adaptive radiations large and small can be attributed to conventional forces such as mutation and diversifying natural selection due to competition. I then address recent claims that the molecular features of metazoan development are the result of clade-level selection for evolvability, and suggest that these features can be more easily explained by conventional individual-level selection for the suppression of deleterious pleiotropic effects. Finally, I ask what must be known if we are to understand the ultimate causes of molecular and developmental diversity.

Biological Evolution↗

Convergent evolution of gene expression in two high-toothed stickleback populations.

Changes in developmental gene regulatory networks enable evolved changes in morphology. These changes can be in cis regulatory elements that act in an allele-specific manner, or changes to the overall trans regulatory environment that interacts with cis regulatory sequences. Here we address several questions about the evolution of gene expression accompanying a convergently evolved constructive morphological trait, increases in tooth number in two independently derived freshwater populations of threespine stickleback fish (Gasterosteus aculeatus). Are convergently evolved cis and/or trans changes in gene expression associated with convergently evolved morphological evolution? Do cis or trans regulatory changes contribute more to gene expression changes accompanying an evolved morphological gain trait? Transcriptome data from dental tissue of ancestral low-toothed and two independently derived high-toothed stickleback populations revealed significantly shared gene expression changes that have convergently evolved in the two high-toothed populations. Comparing cis and trans regulatory changes using phased gene expression data from F1 hybrids, we found that trans regulatory changes were predominant and more likely to be shared among both high-toothed populations. In contrast, while cis regulatory changes have evolved in both high-toothed populations, overall these changes were distinct and not shared among high-toothed populations. Together these data suggest that a convergently evolved trait can occur through genetically distinct regulatory changes that converge on similar trans regulatory environments.

Alleles↗

Molecular evolution of a portion of the mitochondrial 16S ribosomal gene region in scleractinian corals.

Relationships among families and suborders of scleractinian corals are poorly understood because of difficulties 1) in making inferences about the evolution of the morphological characters used in coral taxonomy and 2) in interpreting their 240-million-year fossil record. Here we describe patterns of molecular evolution in a segment of the mitochondrial (mt) 16S ribosomal gene from taxa of 14 families of corals and the use of this gene segment in a phylogenetic analysis of relationships within the order. We show that sequences obtained from scleractinians are homologous to other metazoan 16S ribosomal sequences and fall into-two distinct clades defined by size of the amplified gene product. Comparisons of sequences from the two clades demonstrate that both sets of sequences are evolving under similar evolutionary constraints: they do not differ in nucleotide composition, numbers of transition and transversion substitutions, spatial patterns of substitutions, or in rates of divergence. The characteristics and patterns observed in these sequences as well as the secondary structures, are similar to those observed in mt 16S ribosomal DNA sequences from other taxa. Phylogenetic analysis of these sequences shows that they are useful for evaluating relationships within the order. The hypothesis generated from this analysis differs from traditional hypotheses for evolutionary relationships among the Scleractinia and suggests that a reevaluation of evolutionary affinities in the order is needed.

Animals↗

Alternative adaptations, speciation, and phylogeny (A Review).

Alternative adaptations-different adaptive phenotypes maintained in the same life stage and the same population but not necessarily simultaneously expressed in the same individual-represent contrasting character sets produced by the same genome, in effect allowing a single species to occupy more than one sympatric niche. Such alternatives are particularly likely to give rise to novel adaptations because of selection for extreme dissimilarity between them and because established traits buffer populations against extinction while independently expressed alternatives evolve in new directions. Particular alternatives can be suddenly fixed in populations with little or no genetic change, leading to a period of rapid evolution (especially, of morphology) exaggerating the characteristics of the newly fixed form. This burst of change would facilitate rapid speciation and could produce "punctuated" patterns of evolution. Evidence from a wide variety of organisms shows that alternative phenotypes are exceedingly common in nature and that they are probably important in speciation and macroevolution. Although many of these ideas and observations have been noted piecemeal by previous authors, bringing them together demonstrates the probable importance of alternative adaptations in the origin of major evolutionary novelties and calls for a revision of current and traditional ideas about the role of behavior and ontogeny in the genesis of organic diversity.

Journal Article↗

Direct regulation of knot gene expression by Ultrabithorax and the evolution of cis-regulatory elements in Drosophila.

The regulation of development by Hox proteins is important in the evolution of animal morphology, but how the regulatory sequences of Hox-regulated target genes function and evolve is unclear. To understand the regulatory organization and evolution of a Hox target gene, we have identified a wing-specific cis-regulatory element controlling the knot gene, which is expressed in the developing Drosophila wing but not the haltere. This regulatory element contains a single binding site that is crucial for activation by the transcription factor Cubitus interruptus (Ci), and a cluster of binding sites for repression by the Hox protein Ultrabithorax (UBX). The negative and positive control regions are physically separable, demonstrating that UBX does not repress by competing for occupancy of Ci-binding sites. Although knot expression is conserved among Drosophila species, this cluster of UBX binding sites is not. We isolated the knot wing cis-regulatory element from D. pseudoobscura, which contains a cluster of UBX-binding sites that is not homologous to the functionally defined D. melanogaster cluster. It is, however, homologous to a second D. melanogaster region containing a cluster of UBX sites that can also function as a repressor element. Thus, the knot regulatory region in D. melanogaster has two apparently functionally redundant blocks of sequences for repression by UBX, both of which are widely separated from activator sequences. This redundancy suggests that the complete evolutionary unit of regulatory control is larger than the minimal experimentally defined control element. The span of regulatory sequences upon which selection acts may, in general, be more expansive and less modular than functional studies of these elements have previously indicated.

Animals↗

Repression and loss of gene expression outpaces activation and gain in recently duplicated fly genes.

Evolutionists widely acknowledge that regulatory genetic changes are of paramount importance for morphological and genomic evolution. Nevertheless, mechanistic complexity and a paucity of data from nonmodel organisms have prevented testing and quantifying universal hypotheses about the macroevolution of gene regulatory mechanisms. Here, we use a phylogenetic approach to provide a quantitative demonstration of a previously hypothesized trend, whereby the evolutionary rate of repression or loss of gene expression regions is significantly higher than the rate of activation or gain. Such a trend is expected based on case studies in regulatory evolution and under models of molecular evolution where duplicated genes lose duplicated expression patterns in a complementary fashion. The trend is important because repression of gene expression is a hypothesized mechanism for the origin of evolutionarily novel morphologies through specialization.

Animals↗

Shape evolution of lead telluride and selenide nanostructures under different hydrothermal synthesis conditions.

Face-open nanoboxes of lead telluride and selenide have been synthesized by a simple hydrothermal method. Nano- and microcrystals of various morphologies, including microflowers, semi-microflowers, cubic nanoparticles, etc., have also been observed at different synthesis conditions. Temperature, time, and concentrations of various reactants play a major role in controlling the morphology and shape evolution of the product. This simple synthesis technique for the growth of various nano- and microstructures opens a new route to prepare hierarchical structures of a variety of binary semiconducting materials in a large quantity. A possible growth mechanism of such nano- and microstructures has been proposed.

Crystallization↗

Postmating sexual selection: allopatric evolution of sperm competition mechanisms and genital morphology in calopterygid damselflies (Insecta: Odonata).

Postmating sexual selection theory predicts that in allopatry reproductive traits diverge rapidly and that the resulting differentiation in these traits may lead to restrictions to gene flow between populations and, eventually, reproductive isolation. In this paper we explore the potential for this premise in a group of damselflies of the family Calopterygidae, in which postmating sexual mechanisms are especially well understood. Particularly, we tested if in allopatric populations the sperm competition mechanisms and genitalic traits involved in these mechanisms have indeed diverged as sexual selection theory predicts. We did so in two different steps. First, we compared the sperm competition mechanisms of two allopatric populations of Calopteryx haemorrhoidalis (one Italian population studied here and one Spanish population previously studied). Our results indicate that in both populations males are able to displace spermathecal sperm, but the mechanism used for sperm removal between both populations is strikingly different. In the Spanish population males seem to empty the spermathecae by stimulating females, whereas in the Italian population males physically remove sperm from the spermathecae. Both populations also exhibit differences in genital morphometry that explain the use of different mechanisms: the male lateral processes are narrower than the spermathecal ducts in the Italian population, which is the reverse in the Spanish population. The estimated degree of phenotypic differentiation between these populations based on the genitalic traits involved in sperm removal was much greater than the differentiation based on a set of other seven morphological variables, suggesting that strong directional postmating sexual selection is indeed the main evolutionary force behind the reproductive differentiation between the studied populations. In a second step, we examined if a similar pattern in genital morphometry emerge in allopatric populations of this and other three species of the same family (Calopteryx splendens, C. virgo and Hetaerina cruentata). Our results suggest that there is geographic variation in the sperm competition mechanisms in all four studied species. Furthermore, genitalic morphology was significantly divergent between populations within species even when different populations were using the same copulatory mechanism. These results can be explained by probable local coadaptation processes that have given rise to an ability or inability to reach and displace spermathecal sperm in different populations. This set of results provides the first direct evidence of intraspecific evolution of genitalic traits shaped by postmating sexual selection.

Animals↗

Number of ancestral human species: a molecular perspective.

Despite the remarkable developments in molecular biology over the past three decades, anthropological genetics has had only limited impact on systematics in human evolution. Genetics offers the opportunity to objectively test taxonomies based on morphology and may be used to supplement conventional approaches to hominid systematics. Our analyses, examining chromosomes and 46 estimates of genetic distance, indicate there may have been only around 4 species on the direct line to modern humans and 5 species in total. This contrasts with current taxonomies recognising up to 23 species. The genetic proximity of humans and chimpanzees has been used to suggest these species are congeneric. Our analysis of genetic distances between them is consistent with this proposal. It is time that chimpanzees, living humans and all fossil humans be classified in Homo. The creation of new genera can no longer be a solution to the complexities of fossil morphologies. Published genetic distances between common chimpanzees and bonobos, along with evidence for interbreeding, suggest they should be assigned to a single species. The short distance between humans and chimpanzees also places a strict limit on the number of possible evolutionary 'side branches' that might be recognised on the human lineage. All fossil taxa were genetically very close to each other and likely to have been below congeneric genetic distances seen for many mammals. Our estimates of genetic divergence suggest that periods of around 2 million years are required to produce sufficient genetic distance to represent speciation. Therefore, Neanderthals and so-called H. erectus were genetically so close to contemporary H. sapiens they were unlikely to have been separate species. Thus, it is likely there was only one species of human (H. sapiens) for most of the last 2 million years. We estimate the divergence time of H. sapiens from 16 genetic distances to be around 1.7 Ma which is consistent with evidence for the earliest migration out of Africa. These findings call into question the mitochondrial "African Eve" hypothesis based on a far more recent origin for H. sapiens and show that humans did not go through a bottleneck in their recent evolutionary history. Given the large offset in evolutionary rates of molecules and morphology seen in human evolution, Homo species are likely to be characterised by high levels of morphological variation and low levels of genetic variability. Thus, molecular data suggest the limits for intraspecific morphological variation used by many palaeoanthropologists have been set too low. The role of phenotypic plasticity has been greatly underestimated in human evolution. We call into question the use of mtDNA for studies of human evolution. This DNA is under strong selection, which violates the assumption of selective neutrality. This issue should be addressed by geneticists, including a reassessment of its use for molecular clocks. There is a need for greater cooperation between palaeoanthropologists and anthropological geneticists to better understand human evolution and to bring palaeoanthropology into the mainstream of evolutionary biology.

Animals↗

[Swine cell sublines with different ploidies. I. Karyotypic evolution].

Two swine kidney cell sublines, one of them IB-RS-10-I, with diploid level of chromosomes and the other, IB-RS-10-II, with tetraploid level, were studied as far as their morphology and karyotypic evolution was concerned. Both of them derived from the parental cell line after seven months in continuous culture and maintained in the same type of nutrient medium showed peculiar chromosome alterations for each subline, though in both sublines were observed losses of chromosomes belonging to the gruop GIV.

Animals↗

Systematic prediction of kinetically limited crystal growth morphologies.

We develop a new, combined experimental and theoretical approach to make reliable predictions for the limiting case of surface reaction kinetics controlled growth. We solve the inverse problem of determining the growth velocity from observations of the evolution of the morphology of GaN islands grown by metalorganic chemical vapor deposition and make use of crystal symmetry and established theorems. We are able to predict the growth for both convex and concave surfaces, with faceted and curved features. We also give a general guideline for deducing growth velocities from experimental observations.

Journal Article↗

The UBX-regulated network in the haltere imaginal disc of D. melanogaster.

Hox proteins have been proposed to act at multiple levels within regulatory hierarchies and to directly control the expression of a plethora of target genes. However, for any specific Hox protein or tissue, very few direct in vivo-regulated target genes have been identified. Here, we have identified target genes of the Hox protein Ultrabithorax (UBX), which modifies the genetic regulatory network of the wing to generate the haltere, a modified hindwing. We used whole-genome microarrays and custom arrays including all predicted transcription factors and signaling molecules in the Drosophila melanogaster genome to identify differentially expressed genes in wing and haltere imaginal discs. To elucidate the regulation of selected genes in more detail, we isolated cis-regulatory elements (CREs) for genes that were specifically expressed in either the wing disc or haltere disc. We demonstrate that UBX binds directly to sites in one element, and these sites are critical for activation in the haltere disc. These results indicate that haltere and metathoracic segment morphology is not achieved merely by turning off the wing and mesothoracic development programs, but rather specific genes must also be activated to form these structures. The evolution of haltere morphology involved changes in UBX-regulated target genes, both positive and negative, throughout the wing genetic regulatory network.

Animals↗