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Emergence of salivary gland cell lineage diversity suggests a role for androgen-independent epidermal growth factor receptor signaling.

Diversity of cell lineages within glandular organs is generated postnatally by differentiation of committed progenitor cells. Fundamental regulatory aspects of this process are not understood. The mouse submandibular salivary gland (SSG) served as model to assess the role of epidermal growth factor (EGF) receptor signaling during emergence of cell lineage diversity. Temporal fluctuations in EGF receptor mRNA levels coincident with crucial differentiative cell lineage transitions were revealed by RNase protection analyses. Between days 2 and 5, when proacinar cells are maturing and striated duct cells emerge, EGF receptor mRNA levels were highest and all differentiating cells exhibited EGF receptor immunoreactivity. EGF receptor mRNA levels then declined sharply and immunoreactivity became confined to ductal cells. At day 11 in male mice, and days 11 and 16 in females, a second increase in EGF receptor mRNA was detected coincident with emergence of granular convoluted tubule (GCT) cells. With completion of androgen-dependent GCT cell differentiation at the onset of puberty, EGF receptor mRNA levels and intensity of immunoreactivity decreased. Androgen effects on EGF receptor mRNA or immunoreactivity could not be detected. These temporally distinct patterns of EGF receptor expression suggest that this signaling pathway is a mechanism of potential importance in emergence of cell lineage diversity in a glandular organ.

Androgens↗

Smooth Muscle Lineage Diversity in the Chick Embryo

Lineage analysis studies in the avian embryo have identified two types of smooth muscle cells (SMCs) in the tunica media of large elastic arteries; one that originates within the cardiac neural crest and is ectoderm in origin (Ect) and another that arises from local mesenchyme of mesodermal origin (Mes). To determine if differences in primary embryonic lineage can give rise to SMCs with stable differences in growth and differentiation properties, we isolated Ect and Mes SMCs from the Day 14 chick embryo aorta. We report that despite different primary embryonic origins, Ect and Mes SMCs express nearly identical levels of seven SMC differentiation markers in vitro, consistent with their common smooth muscle developmental fates in vivo. By contrast, Ect SMCs displayed a greater capacity for growth in serum-free medium than Mes SMCs, but only under conditions permitting short-range cell-cell interactions. Most of the peptide growth factors tested that might account for serum-independent growth (PDGF-AA, PDGF-BB, basic FGF, EGF, or activin) stimulated DNA synthesis to similar extents in Ect and Mes SMCs. However, we found dramatic, lineage-dependent differences in SMC responses to transforming growth factor-beta (TGF-beta). Exposure to TGF-beta1 (0.4 to 400 pmole/liter) consistently increased DNA synthesis in Ect SMCs, whereas in paired cultures of Mes SMCs, TGF-beta1 was growth inhibitory. In SMC cultures transfected with p3TP-lux, a luciferase reporter controlled by the TGF-beta1-response elements of the human PAI-1 promoter, TGF-beta1 (120 pM) produced 12 ± 2-fold increases in luciferase activity in Ect SMCs and only 3 ± 1.5-fold increases in Mes SMCs. Analysis of TGF-beta receptor phenotypes by Northern blot, radioligand binding, and crosslinking assays showed that Ect and Mes SMCs expressed similar levels of types I, II, and III TGF-beta receptors. However, using a polyclonal antibody specific for the chick type II TGF-beta receptor subunit, we demonstrate that Mes SMCs produce a fully glycosylated form of this protein while Ect SMCs elaborate only an unglycosylated type II TGF-beta receptor. These results show that Ect and Mes SMCs exhibit lineage-dependent differences in growth and receptor-mediated transcriptional responses to at least one important class of SMC morphogens and growth modifiers, e.g., the TGF-betas. Our findings suggest that different SMC populations within a common vessel wall may respond in lineage-dependent ways to signals that direct formation of the tunica media in the embryo and to factors involved in the progression of vascular disease later in life.

Journal Article↗

The analysis of near full-length genome sequences of human immunodeficiency virus type 1 BF intersubtype recombinant viruses from Chile, Venezuela and Spain reveals their relationship to diverse lineages of recombinant viruses related to CRF12_BF.

Human immunodeficiency virus type 1 (HIV-1) BF intersubtype recombinant viruses are common in Argentina and Uruguay, where CRF12_BF and related recombinants are frequently found, and, in a lower proportion, in Brazil. Full-length genome sequences have been characterized in several of these recombinant viruses. Here, we analyze six newly derived near full-length genome sequences of BF recombinant viruses, three from Chile, one from Venezuela and two from Spain. Five of them had known epidemiological links to Argentina. Genomes were amplified by PCR from plasma RNA or from peripheral blood mononuclear cells' DNA. Mosaic structures and phylogenetic relationships were analyzed by bootscanning, neighbour-joining phylogenetic trees and by examination of subtype signature nucleotides. One virus from Spain had a mosaic structure fully coincident with CRF12_BF. The others had unique mosaic structures, except the viruses from two Chilean sisters infected vertically from the same mother, who showed identical recombination patterns. Each of the unique recombinants had one to six breakpoints coincident with CRF12_BF and three also had two or three breakpoints coincident with a previously characterized unique recombinant from Argentina (A025) related to CRF12_BF. A phylogenetic tree of concatenated subtype F segments supported the relationship of five recombinants with CRF12_BF. In trees of partial subtype F and B segments, four recombinants clustered with A025. The examination of CRF12_BF signature amino acids and nucleotides supported the common ancestry of all the analyzed viruses. Based on these results, a model of generation of HIV-1 BF recombinants of Argentinean ancestry by successive rounds of recombination along diverse lineages deriving from a common BF recombinant ancestor related to CRF12_BF is proposed.

Argentina↗

Snapshot Genomic Surveillance Reveals Insights into Antimicrobial Resistance and Lineage Diversity of Uropathogens in Older Adults in Queensland.

BACKGROUND: Community-acquired urinary tract infections (UTIs) are a significant health concern in older adults. However, few studies have investigated the epidemiology of uropathogens across diverse settings where older adults reside. METHODS: In this study, we whole-genome sequenced urinary isolates of Escherichia coli, Klebsiella species, and Enterobacter cloacae complex collected from individuals aged 70 and over living in the community and residential aged care facilities (RACFs) in Queensland, Australia. We investigated the prevalence of antimicrobial resistance (AMR), pathogen population structure, and transmission dynamics across the settings. RESULTS: E. coli was most frequently identified (82.2%, 447/544), followed by K. pneumoniae (10.8%, 59/544) and E. hormaechei (2.6%, 14/544). Intraspecies lineages were diverse, and a total of 177 sequence types were identified. The three predominant lineages were E. coli ST73 (10.7%, 54/504), ST95 (8.1%, 41/504), and ST131 (5.4%, 27/504). Transmission events were minimal, being identified in 13 patients (2.5%), mainly from the community. The resistance rate to antibiotics was low, with only a small proportion (9.7%) of multidrug-resistant (MDR) isolates. The predominant MDR lineage was E. coli ST131, which carried extended-spectrum beta-lactamase bla CTX-M genes. CONCLUSIONS: Community-acquired UTIs in older adults are predominantly caused by diverse E. coli lineages, with limited evidence of transmission within aged care facilities. The low rates of AMR in the community, along with the absence of strains adapted to a particular setting, suggest that current empiric therapy guidelines remain appropriate. Our prospective genomic surveillance offers valuable insights for monitoring UTIs in this population. It demonstrates the importance of an unbiased approach to accurately capture the prevalence and diversity of uropathogen lineages.

Enterobacteriaceae↗

Lineage diversity in the Drosophila nervous system.

The detailed descriptions of cellular lineages in the Drosophila nervous system have provided the foundations for an in-depth genetic analysis of the mechanisms that regulate fate decisions at every cell cycle.

Animals↗

Metabolic labeling of a subset of glial cells by UDP-galactose: implication for astrocyte lineage diversity.

Astrocytes are implicated in many aspects of brain function; however, it remains unclear whether astrocytes arise from a single cell lineage. It is therefore important to obtain new markers for the astrocyte cell lineage. We show that exogenously added UDP-galactose (UDP-Gal) can be used to metabolically label a subset of glial fibrillary acidic protein-positive (GFAP+) cells. UDP-Gal was incorporated into the cultured embryonic mouse brain slices in a time-dependent manner. Surprisingly, the transferred sugar moiety was no longer Gal but was mainly glucose. Most of the radioactivity was transferred to a polymer of glucose, most likely to be glycogen, and also to glucosyl ceramide. In the slice culture, the reaction products were distributed densely in the ventricular zone and also on process-like structures extending to the pial surface. In dissociation culture, UDP-Gal labeled some of the GFAP+ cells and some of the vimentin+ cells. Because radial glial cells (RGCs) contain glycogen and change from vimentin+ to GFAP+, it is strongly suggested that UDP-Gal labeled RGCs and their descendants. Only 27% of the GFAP+ cells were labeled with UDP-Gal, which suggests that only a subset of astrocytes are derived from RGCs and that there is a discrete group of GFAP+ cells that is not generated from RGCs.

Animals↗

Smooth muscle lineage diversity in the chick embryo. Two types of aortic smooth muscle cell differ in growth and receptor-mediated transcriptional responses to transforming growth factor-beta.

Lineage analysis studies in the avian embryo have identified two types of smooth muscle cells (SMCs) in the tunica media of large elastic arteries; one that originates within the cardiac neural crest and is ectoderm in origin (Ect) and another that arises from local mesenchyme of mesodermal origin (Mes). To determine if differences in primary embryonic lineage can give rise to SMCs with stable differences in growth and differentiation properties, we isolated Ect and Mes SMCs from the Day 14 chick embryo aorta. We report that despite different primary embryonic origins, Ect and Mes SMCs express nearly identical levels of seven SMC differentiation markers in vitro, consistent with their common smooth muscle developmental fates in vivo. By contrast, Ect SMCs displayed a greater capacity for growth in serum-free medium than Mes SMCs, but only under conditions permitting short-range cell-cell interactions. Most of the peptide growth factors tested that might account for serum-independent growth (PDGF-AA, PDGF-BB, basic FGF, EGF, or activin) stimulated DNA synthesis to similar extents in Ect and Mes SMCs. However, we found dramatic, lineage-dependent differences in SMC responses to transforming growth factor-beta (TGF-beta). Exposure to TGF-beta 1 (0.4 to 400 pmole/liter) consistently increased DNA synthesis in Ect SMCs, whereas in paired cultures of Mes SMCs, TGF-beta 1 was growth inhibitory. In SMC cultures transfected with p3TP-lux, a luciferase reporter controlled by the TGF-beta 1-response elements of the human PAI-1 promoter, TGF-beta 1 (120 pM) produced 12 +/- 2-fold increases in luciferase activity in Ect SMCs and only 3 +/- 1.5-fold increases in Mes SMCs. Analysis of TGF-beta receptor phenotypes by Northern blot, radioligand binding, and crosslinking assays showed that Ect and Mes SMCs expressed similar levels of types I, II, and III TGF-beta receptors. However, using a polyclonal antibody specific for the chick type II TGF-beta receptor subunit, we demonstrate that Mes SMCs produce a fully glycosylated form of this protein while Ect SMCs elaborate only an unglycosylated type II TGF-beta receptor. These results show that Ect and Mes SMCs exhibit lineage-dependent differences in growth and receptor-mediated transcriptional responses to at least one important class of SMC morphogens and growth modifiers, e.g., the TGF-betas. Our findings suggest that different SMC populations within a common vessel wall may respond in lineage-dependent ways to signals that direct formation of the tunica media in the embryo and to factors involved in the progression of vascular disease later in life.

Animals↗

High lineage diversity and host sharing of malarial parasites in a local avian assemblage.

Bird populations often have high prevalences of the haemosporidians Haemoproteus spp. and Plasmodium spp., but the extent of host sharing and host switching among these parasite lineages and their avian hosts is not well known. While sampling within a small geographic region in which host individuals are likely to have been exposed to the same potential parasite lineages, we surveyed highly variable mitochondrial DNA from haemosporidians isolated from 14 host taxa representing 4 avian families (Hirundinidae, Parulidae, Emberizidae, and Fringillidae). Analyses of cytochrome b sequences from 83 independent infections identified 29 unique haplotypes, representing 2 well-differentiated Haemoproteus spp. lineages and 6 differentiated Plasmodium spp. lineages. A phylogenetic reconstruction of relationships among these lineages provided evidence against host specificity at the species and family levels, as all haemosporidian lineages recovered from 2 or more host individuals (2 Haemoproteus and 3 Plasmodium lineages) were found in at least 2 host families. We detected a similar high level of host sharing; the 3 most intensively sampled host species each harbored 4 highly differentiated haemosporidian lineages. These results indicate that some Haemoproteus spp. and Plasmodium spp. lineages exhibit a low degree of host specificity, a phenomenon with implications for ecological and evolutionary interactions among these parasites and their hosts.

Animals↗

Mechanisms regulating lineage diversity during mammalian cerebral cortical neurogenesis and gliogenesis.

During mammalian cerebral cortical development, neural stem cells (NSCs) present within periventricular generative zones give rise to successive waves of neurons and radial glia, followed by oligodendrocytes and astrocytes. The molecular and cellular mechanisms that orchestrate these precisely timed and progressive maturational events are still largely undefined. These developmental processes are likely to involve the dynamic interplay of environmental signals, cell-cell interactions and transcriptional regulatory events. The bone morphogenetic proteins (BMPs), an expanding subclass of the transforming growth factor beta cytokine superfamily, may represent an important set of environmental cues for these progressive maturational events because of the broad profiles of developmental expression of the requisite BMP ligands, receptor subunits and intracellular transduction elements, and because of their versatile roles in promoting a spectrum of cellular processes intimately involved in progressive neural fate decisions. The BMPs also interact with complementary regional environmental signals such as the basic fibroblast growth factor (bFGF) and sonic hedgehog (Shh) that promote earlier stages of NSC expansion, self-renewal, lineage restriction and incipient lineage commitment. The ability of these cytokines and trophic signals to act within specific neurodevelopmental contexts may, in turn, depend on the composite actions of cell-cell contact-associated signals, such as Notch-Hes-mediated lateral inhibitory pathways, and additional transcriptional modulatory events, such as those mediated by members of the inhibitor of differentiation (ID) gene family that encode a novel set of negative basic helix-loop-helix (bHLH) transcription factors. In this chapter, we will examine the distinct roles of these different classes of developmental cues in defining the biological properties of an integrated cerebral cortical developmental signaling network. Ongoing studies in this exciting area of mammalian central nervous system (CNS) development will help to identify important molecular and cellular targets for evolving pharmacological, gene and stem cell therapeutic interventions to combat the pathological sequelae of a spectrum of acquired and genetic disorders of the central nervous system.

Animals↗

Restriction fragment length polymorphisms detected with novel DNA probes differentiate among diverse lineages of serogroup 4 Listeria monocytogenes and identify four distinct lineages in serotype 4b.

Listeria monocytogenes of serotype 4b has been implicated in numerous outbreaks of food-borne listeriosis and in ca. 40% of sporadic cases. Strains of this serotype appear to be relatively homogeneous genetically, and molecular markers specific for distinct serotype 4b lineages have not been frequently identified. Here we show that DNA fragments derived from the putative mannitol permease locus of Listeria monocytogenes had an unexpectedly high potential to differentiate among different strains of serotype 4b when used as probes in Southern blotting of EcoRI-digested genomic DNA, yielding four distinct restriction fragment length polymorphism (RFLP) patterns. Strains of two epidemic-associated lineages, including the major epidemic clone implicated in several outbreaks in Europe and North America, had distinct RFLPs which differed from those of all other serotype 4b strains that we screened but which were encountered among strains of serotypes 1/2b and 3b. In addition, three serogroup 4 lineages were found to have unique RFLPs that were not encountered among any other L. monocytogenes strains. One was an unusual lineage of serotype 4b, and the other two were members of the serotype 4a and 4c group. The observed polymorphisms may reflect evolutionary relationships among lineages of L. monocytogenes and may facilitate detection and population genetic analysis of specific lineages.

Bacterial Typing Techniques↗

Synchronous synthesis of alpha- and beta-chemokines by cells of diverse lineage in the central nervous system of mice with relapses of chronic experimental autoimmune encephalomyelitis.

Chemokines are secreted peptides that exhibit selective chemoattractant properties for target leukocytes. Two subfamilies, alpha- and beta-chemokines, have been described, based on structural, genetic, and functional considerations. In acute experimental autoimmune encephalomyelitis (EAE), chemokines are up-regulated systemically and in central nervous system (CNS) tissues at disease onset. Functional significance of this expression was supported by other studies; intervention with an antichemokine antibody abrogated passive transfer of EAE, and chemokines expressed in brains of transgenic mice recruited appropriate leukocyte populations into the CNS compartment. Chemokine expression in the more relevant circumstance of chronic EAE has not been addressed. We monitored the time course and cellular sources of chemokines (monocyte chemoattractant protein-1, macrophage inflammatory protein-1 alpha, interferon-gamma-inducible protein of 10 kd, KC, and regulated on activation, normal T-cell expressed and secreted cytokine) in CNS and peripheral tissues during spontaneous relapses of chronic EAE. We found coordinate chemokine up-regulation in brain and spinal cord during clinical relapse, with expression confined to CNS tissues. Monocyte chemoattractant protein-1, interferon-gamma-inducible protein of 10 kd, and KC were synthesized by astrocytic cells, whereas macrophage inflammatory protein-1 alpha and regulated on activation, normal T-cell expressed and secreted cytokine were elaborated by infiltrating leukocytes. The results demonstrate stringent regulation of multiple chemokines in vivo during a complex organ-specific autoimmune disease. We propose that chemokine expression links T-cell antigen recognition and activation to subsequent CNS inflammatory pathology in chronic relapsing EAE.

Animals↗

Diversification of haematopoietic stem cells to specific lineages.

Diverse types of blood cell (lineages) are produced from rare haematopoietic stem cells that reside in the bone marrow. This process, known as haematopoiesis, provides a valuable model for examining how genetic programs are established and executed in vertebrates, and also how homeostasis of blood formation is altered in leukaemias. So, how does an apparently small group of critical lineage-restricted nuclear regulatory factors specify the diversity of haematopoietic cells? Recent findings not only indicate how this may be achieved but also show the extraordinary plasticity of tissue stem cells in vivo.

Animals↗

Modern Quaternary plant lineages promote diversity through facilitation of ancient Tertiary lineages.

One of the most important floristic sorting periods to affect modern plant communities occurred during the shift from the wet Tertiary period to the unusually dry Quaternary, when most global deserts developed. During this time, a wave of new plant species emerged, presumably in response to the new climate. Interestingly, most Tertiary species that have been tracked through the fossil record did not disappear but remained relatively abundant despite the development of a much more unfavorable climate for species adapted to moist conditions. Here we find, by integrating paleobotanical, ecological, and phylogenetic analyses, that a large number of ancient Tertiary species in Mediterranean-climate ecosystems appear to have been preserved by the facilitative or "nurse" effects of modern Quaternary species. Our results indicate that these interdependent relationships among plants have played a central role in the preservation of the global biodiversity and provided a mechanism for stabilizing selection and the conservation of ecological traits over evolutionary time scales.

Biodiversity↗

Teleost fish genomes contain a diverse array of L1 retrotransposon lineages that exhibit a low copy number and high rate of turnover.

Retrotransposable elements exhibit a wide range of variation in population dynamics, abundance, and lineage diversity among host genomes across taxa. This range of diversity is illustrated by a single well-defined constituent monophyletic clade of L1 non-LTR retrotransposons that is shared between mammalian and teleost fish genomes. Despite the clear phylogenetic relationships that exist between mammalian and teleost L1 sequences, these elements exhibit markedly different dynamics within their respective taxa. While mammalian genomes typically contain a single, abundant lineage of L1 elements that traces millions of years of evolution, the zebraflsh genome was recently shown to exhibit a high diversity of ancient lineages coexisting at a very low copy number and apparently exhibiting a high rate of turnover. In the present study, a combination of degenerate PCR, lineage-specific PCR, and genomic Southern blot analysis is utilized to demonstrate high L1 lineage diversity, low copy number, and a high proportion of polymorphic inserts in the genomes of the killifish species, Fundulus heteroclitus. Additional species surveyed by degenerate PCR include Cyprinodon variegatus, Rivulus marmoratus, and Menidia beryllina. These results further support the generality of the differences that exist in host-element dynamics between teleost fish and mammalian genomes with regard to L1 retrotransposons.

Animals↗

Fossil calibrations and molecular divergence time estimates in centrarchid fishes (Teleostei: Centrarchidae).

Molecular clock methods allow biologists to estimate divergence times, which in turn play an important role in comparative studies of many evolutionary processes. It is well known that molecular age estimates can be biased by heterogeneity in rates of molecular evolution, but less attention has been paid to the issue of potentially erroneous fossil calibrations. In this study we estimate the timing of diversification in Centrarchidae, an endemic major lineage of the diverse North American freshwater fish fauna, through a new approach to fossil calibration and molecular evolutionary model selection. Given a completely resolved multi-gene molecular phylogeny and a set of multiple fossil-inferred age estimates, we tested for potentially erroneous fossil calibrations using a recently developed fossil cross-validation. We also used fossil information to guide the selection of the optimal molecular evolutionary model with a new fossil jackknife method in a fossil-based model cross-validation. The centrarchid phylogeny resulted from a mixed-model Bayesian strategy that included 14 separate data partitions sampled from three mtDNA and four nuclear genes. Ten of the 31 interspecific nodes in the centrarchid phylogeny were assigned a minimal age estimate from the centrarchid fossil record. Our analyses identified four fossil dates that were inconsistent with the other fossils, and we removed them from the molecular dating analysis. Using fossil-based model cross-validation to determine the optimal smoothing value in penalized likelihood analysis, and six mutually consistent fossil calibrations, the age of the most recent common ancestor of Centrarchidae was 33.59 million years ago (mya). Penalized likelihood analyses of individual data partitions all converged on a very similar age estimate for this node, indicating that rate heterogeneity among data partitions is not confounding our analyses. These results place the origin of the centrarchid radiation at a time of major faunal turnover as the fossil record indicates that the most diverse lineages of the North American freshwater fish fauna originated at the Eocene-Oligocene boundary, approximately 34 mya. This time coincided with major global climate change from warm to cool temperatures and a signature of elevated lineage extinction and origination in the fossil record across the tree of life. Our analyses demonstrate the utility of fossil cross-validation to critically assess individual fossil calibration points, providing the ability to discriminate between consistent and inconsistent fossil age estimates that are used for calibrating molecular phylogenies.

Animals↗

Contrasting patterns of radiation in African and Australian Restionaceae.

The floras of the Mediterranean-climate areas of southern Africa and southwestern Australia are remarkably species rich. Because the two areas are at similar latitudes and in similar positions on their respective continents, they have probably had similar Cenozoic climatic histories. Here we test the prediction that the evolution of the species richness in the two areas followed a similar temporal progression by comparing the rates of lineage accumulation for African and Australian Restionaceae. Restionaceae (Poales) are typical and often dominant elements in the fynbos vegetation of the Cape Floristic Region of southern Africa and the kwongan vegetation of the Southwestern Floristic Province of Western Australia. The phylogeny of the family was estimated from combined datasets for rbcL and trnL-F sequences and a large morphological dataset; these datasets are largely congruent. The monophyly of Restionaceae is supported and a basal division into an African clade (approximately 350 species) and an Australian clade (146 species) corroborated. There is also support for a futher subdivision of these two large sister-clades, but the terminal resolution within the African clade is very weak. Fossil pollen records provided a minimum age of the common ancestor of Australian and African Restionaceae as 64-71 million years ago, and this date was used to calibrate a molecular clock. A molecular clock was rejected by a likelihood ratio test; therefore, rate changes between the lineages were smoothed using nonparametric rate smoothing. The rate-corrected ages were used to construct a plot of lineages through time. During the Palaeogene the Australian lineage diversity increased consistent with the predictions of the constant birthrate model, while the African lineage diversity showed a dramatic increase in diversification rate in the Miocene. Incomplete sampling obscures the patterns in the Neogene, but extending the trends to the modern extant diversity suggests that this acceleration in the speciation rate continued in the African clade, whereas the Australian clade retained a constant diversification rate. The substantial morphological and anatomical similarity between the African and Australian Restionaceae appear to preclude morphological innovations as possible explanations for the intercontinental differences. Most likely these differences are due to the greater geographical extent and ecological variation in temperate Australia than temperate Africa, which might have provided refugia for basal Restionaceae lineages, whereas the more mountainous terrain of southern Africa might have provided the selective regimes for a more rapid, recent speciation.

Africa↗

Negative selection of the T-cell repertoire: where and when does it occur?

Because of the use of somewhat artificial models for the elucidation of negative selection [superantigen, T-cell receptor (TCR) transgenic mice], there is still considerable uncertainty at what stages of T-cell development negative selection can occur and whether it becomes manifest as developmental arrest, lineage diversion, or induction of apoptotic cell death. Here, experimental evidence is reviewed that excludes developmental arrest and lineage diversion as the sole mechanisms of negative selection. The data emphasize that both CD4+ CD8+ double-positive cortical as well as semi-mature, single-positive, medullary thymocytes are targets of deletion in experimental models employing superantigen and TCR transgenic mice with premature as well as 'timely' onset of TCR expression.

Animals↗

Immigration, species radiation and extinction in a highly diverse songbird lineage: white-eyes on Indian Ocean islands.

Molecular phylogenetic hypotheses of species-rich lineages in regions where geological history can be reliably inferred may provide insights into the scale of processes driving diversification. Here we sample all extant or recently extinct white-eye (Zosterops) taxa of the southwest Indian Ocean, combined with samples from all principal continental lineages. Results support a high dispersal capability, with at least two independent continental sources for white-eyes of the region. An early (within 1.8 million years ago) expansion into the Indian Ocean may have originated either from Asia or Africa; the three resulting lineages show a disparate distribution consistent with considerable extinction following their arrival. Africa is supported as the origin of a later expansion into the region (within 1.2 million years ago). On two islands, a pair of Zosterops species derived from independent immigrations into the Indian Ocean co-occur or may have formerly co-occurred, providing strong support for their origin by double-island colonization rather than within-island (sympatric or microallopatric) speciation. On Mauritius and La Réunion, phylogenetic placement of sympatric white-eyes allow us to rule out a scenario in which independent within-island speciation occurred on both islands; one of the species pairs must have arisen by double colonization, while the other pair is likely to have arisen by the same mechanism. Long-distance immigration therefore appears to be responsible for much of the region's white-eye diversity. Independent immigrations into the region have resulted in lineages with mutually exclusive distributions and it seems likely that competition with congeneric species, rather than arrival frequency, may limit present-day diversity.

Animal Migration↗