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PubMed1992

Genetic divergence, speciation and morphological stasis in a lineage of African cichlid fishes.

Since their discovery at the turn of the century, the species assemblages of cichlid fishes in the East African Lakes Victoria, Malawi and Tanganyika have fascinated evolutionary biologists. Many models have attempted to account for the 'explosive' evolution of several hundred species within these lakes. Here we report a case of surprisingly large genetic divergence among populations of the endemic Tropheus lineage of Lake Tanganyika. This lineage of six species contains twice as much genetic variation as the entire morphologically highly diverse cichlid assemblage of Lake Malawi and six times more variation than the Lake Victoria species flock. Although it is highly variable in coloration, this group of species and its closest relatives have not undergone appreciable morphological change. The observed geographic pattern of genetic variation suggests that major lake level fluctuations affected the distribution and speciation of this lineage of cichlid fishes.

Africa↗
PubMed2026

Comparative mitogenomics of Ocnus glacialis reveals lineage-specific evolutionary rates and complex gene rearrangements in Dendrochirotida.

The order Dendrochirotida (Class Holothuroidea) is a species-rich echinoderm group, yet its internal evolutionary history remains poorly resolved due to limited mitogenomic resources. In this study, we characterized the first complete mitochondrial genome of Ocnus glacialis and conducted comparative analyses to elucidate its phylogenetic position and molecular evolutionary patterns. The circular mitogenome of O. glacialis is 16,776 bp in length, containing the canonical set of 37 genes. Among the analyzed dendrochirotids, O. glacialis exhibited the highest A + T content (70.88%) and a near-zero AT-skew, a compositional profile often linked to lineage-specific evolution in specialized environments. Selection pressure analyses, including branch-model tests, revealed that these compositional features are associated with relaxed purifying selection and an accelerated rate of sequence evolution. Branch-site analyses further identified specific codon sites in cytb, nad2, nad4l, nad5, and nad6 under positive or relaxed constraints. Structurally, O. glacialis displayed the most complex gene rearrangement pattern among the studied species, characterized by multiple tandem duplication-random loss (TDRL) events and extensive intergenic sequences. Furthermore, divergence time estimation suggests that these structural and compositional shifts occurred in tandem with the lineage's diversification. We propose that these mitogenomic signatures reflect a synergistic outcome of habitat transition toward Arctic cold-water and deep-sea environments, coupled with demographic factors such as reduced effective population sizes inherent to its benthic life history. By resolving taxonomic uncertainties, this study provides a robust temporal and molecular framework for understanding the evolutionary history and ecological diversification of the Ocnus lineage.

Animals↗
PubMed2002

Increased heterozygosity for MHC class II lineages in newborn males.

In plants, fungi and marine invertebrates, there are genetic compatibility systems to ensure diversity in the offspring. The importance of genetic compatibility in gametic union and selective abortion in vertebrate animals has also been appreciated recently. There have been suggestions that the major histocompatibility complex (HLA in humans) may be a compatibility system in vertebrates. HLA class II haplotypes often contain a second expressed DRB locus which can be either DRB3, DRB4 or DRB5. These encode the supertypical specificities and mark the ancestral lineages. The members of each lineage have related DNA sequences at the main class II locus HLA-DRB1. We analysed 415 newborns at all expressed DRB loci by PCR analysis to seek evidence for sex-specific prenatal selection events. While there was no significant change in heterozygosity rates between males and females at DRB1, the proportion of males carrying two DRB1 specificities from different ancestral lineages was significantly increased (53.7% in males vs 39.3% in females, P = 0.003). The genotypes consisting of phylogenetically most distinct ones, namely the DRB3 and DRB4 haplotypes, showed the most striking difference between sexes (P = 0.007). These results suggested a more favourable outcome for male concepti heterozygous for supertypical haplotypes. Heterozygosity for most divergent haplotypical families ensures the highest degree of functional heterozygosity at the main HLA class II locus DRB1 while increasing the likelihood of heterozygosity also at other MHC loci. Our observations agree with the previously reported heterozygote excess in male newborn rats and mice. Correlations between MHC class II heterozygosity and advertised male quality in deer and pheasant as well as increased reproductive success in MHC class II heterozygous male macaques are examples of postnatal benefits of heterozygosity in males that may be behind the development of prenatal selection mechanisms. The MHC-mediated prenatal selection of males may also be one of the selective events suggested by the very high primary (male-to-female) sex ratio at fertilization reaching close to unity at birth in humans. These results provide an appealing working hypothesis for further studies in humans and other vertebrates.

Alleles↗
PubMed2000

Detection of acute leukemia cells with mixed lineage leukemia (MLL) gene rearrangements by flow cytometry using monoclonal antibody 7.1.

Translocations involving 11q23 are among the most common genetic abnormalities in hematologic malignancies, occurring in approximately 5-10% of acute lymphoblastic leukemia (ALL) and 5% of acute myeloblastic leukemia (AML). In 11q23 translocations, the mixed lineage leukemia (MLL) gene on chromosome 11, band q23, is usually disrupted. The human homologue of the rat NG2 chondroitin sulfate proteoglycan molecule, as detected by the monoclonal antibody (moab) 7.1, was shown to be expressed on leukemic cells with MLL rearrangements of children with acute leukemia. We further investigated the reactivity of the moab 7.1 on 533 cell samples of adults (n = 215) and children (n = 318) with acute leukemias (271 AML, 217 B-lineage ALL, 37 T-lineage ALL, eight CD7+ CD56+ myeloid/natural killer cell precursor acute leukemias) by flow cytometry. In AML, 38 samples were positive for moab 7.1 ('20%-cut-off-level'). These moab 7.1-positive AML cases revealed a myelomonocytic-differentiated immunophenotype with coexpression of the NK cell marker CD56 in 33 of 38 cases. Two of eight cell samples of the recently described CD7+ CD56+ myeloid/natural killer cell precursor acute leukemia entity reacted with moab 7.1. In ALL, 35 samples mostly of the pro-B-ALL subtype (33 pro-B-ALL, one common-ALL, one pre-B-ALL) were positive for moab 7.1. 58 (81%) of 72 samples with MLL rearrangements were positive for moab 7.1 including 28/31 with a t(4;11), 16/17 with a t(9;11), 3/5 with a t(11;19), and 2/6 with a del(11)(q23). All moab 7.1-positive ALL (n = 34) and childhood AML (n = 17) cases revealed MLL rearrangements as detected by Southern blot analysis and RT-PCR. However, 11 adults with AML, and one adult with moab 7.1-positive CD7+ CD56+ myeloid/natural killer cell precursor acute leukemia were negative for MLL rearrangements as proved by Southern blot analysis. We conclude that moab 7.1 is a sensitive but not entirely specific marker for the identification of 11q23-associated AML and ALL by flow cytometry in children and adults.

Acute Disease↗
PubMed2006

Prostate cancer incidence varies among males from different Y-chromosome lineages.

The incidence rate of prostate cancer in African-American males is two times higher than Caucasian men and ten times higher than Japanese men. The geographical specificity of Y haplogroups implies that males from different ethnic groups undoubtedly have various Y lineages with different Y-chromosomal characteristics that may affect their susceptibility or resistance to such a male-specific cancer. To confirm this hypothesis we studied the Y-chromosomal haplogroups of 92 Japanese prostate cancer patients comparing them with randomly selected 109 unrelated healthy Japanese male controls who were confirmed to be residents of the same geographical area. Males could be classified using three binary Y-chromosome markers (sex-determining region Y (SRY), YAP, 47z) into four haplogroups DE, O2b(*), O2b1, and untagged group. Our results confirmed that prostate cancer incidence varies among males from different Y-chromosome lineages. Males from DE and the untagged haplogroups are at a significantly higher risk to develop prostate cancer than O2b(*) and O2b1 haplogroups (P=0.01), odds ratio 2.17 and 95% confidence interval (1.16-4.07). Males from haplogroup DE are over-represented in the patient group showing a percentage of 41.3%. The underlying possible causes of susceptibility variations of different Y lineages for such a male-specific cancer tumorigenesis are discussed. These findings explain the lower incidence of prostate cancer in Japanese and other South East Asian males than other populations. To our knowledge, this is the first reliable study examining the association between prostate cancer and Y-chromosomal haplogroups, comparing prostate cancer patients with carefully selected matched controls.

Carcinoma↗
PubMed1992

Scavenger-receptor-mediated delivery of daunomycin elicits selective toxicity towards neoplastic cells of macrophage lineage.

Transformed cells of macrophage lineage such as J774A.1, P388D1 and IC21 take up and degrade a conjugate of the antineoplastic drug, daunomycin, with maleylated BSA with high efficiency and saturation kinetics through the scavenger receptors expressed on the surface of these cells. By contrast, transformed cells of non-macrophage lineage, namely L929, EL4, Bowes melanoma and CHO (Chinese-hamster ovary), do not take up and degrade the conjugate, indicating that these cells are scavenger-receptor-deficient. In the conjugated form, about 0.1 microM-daunomycin cause 50% inhibition in the uptake of [3H]thymidine by the receptor-bearing J774A.1 cells, whereas the receptor-deficient Bowes-melanoma cells are not affected. Free daunomycin (0.1 microM) does not significantly affect the uptake of [3H]thymidine by either cell type. Treatment of cells derived from intraperitoneal tumours induced in BALB/C mice by J774A.1 cells with 0.4 microM-daunomycin in the conjugated form for 5 h abolished their ability to form tumours in BALB/C mice. By contrast, transplantation of untreated cells or cells treated with free daunomycin under identical conditions led to tumour formation and subsequent death of the BALB/C mice. These results indicate that this modality for selective elimination of scavenger-receptor-bearing neoplastic cells may be useful for the treatment of histiocytic malignancies in which cells of macrophage lineage turn malignant.

Albumins↗
PubMed1998

Detection of minimal residual disease in B-lineage acute lymphoblastic leukaemia by quantitative flow cytometry.

The clinical significance of detecting minimal residual disease (MRD) in B-lineage acute lymphoblastic leukaemia (ALL) was evaluated by quantitative flow cytometry using a combination of TdT with CD10 and CD19. 53 patients with B-cell precursor ALL were followed during and after completion of treatment (median follow-up 23 months). Nine patients relapsed and MRD had been detected in six of them, 5-15 weeks before relapse despite morphological complete remission. 43 patients remain in clinical remission and in none of these was MRD detected. Disease-free survival based on the detection of MRD by flow cytometry showed a statistically significant difference between both groups (P<0.0001). The absence of MRD correlates with a low relapse rate, whereas the presence of MRD predicted early relapse. This study has shown that flow cytometry can improve the morphologic assessment of bone marrow (BM) remission status in B-lineage ALL. The finding of < 5% blasts in BM aspirates did not correlate with 'true' remission in a proportion of cases as residual leukaemic blasts were detected by flow cytometry in nine samples from six patients. On the other hand, the presence of > 5% blasts assessed by morphology was not necessarily a feature of relapse in five patients as these cells were shown to have a phenotype identical to normal TdT-negative B-cell precursors. Quantitative flow cytometry was more informative than conventional morphology to assess remission status and showed a strong correlation with clinical outcome. This methodology is useful to define MRD in the majority of patients with B-lineage ALL and should be tested in prospective clinical trials.

Adult↗
PubMed1999

Selection and transplantation of autologous CD34+ B-lineage negative cells in advanced-phase multiple myeloma patients: a pilot study.

The feasibility of sequential positive and negative selection of mobilized CD34+ B-lineage negative cells to achieve tumour-free autografts in multiple myeloma (MM) patients was evaluated. Peripheral blood stem cells (PBSC) of 14 patients with advanced disease were mobilized. CD34+ cells were enriched in 12 of the patients by the avidin-biotin immunoabsorption technique. Subsequently, CD10+, CD19+, CD20+ and CD56+ cells (B-lin cells) were removed by immunomagnetic depletion. Minimal residual disease (MRD) was detected by flow cytometry and PCR-based molecular analysis of the patient specific IgH complementary-determining region III (CDRIII). Positive selection of stem cells produced a median recovery of 54.7% of the initial content of CD34+ cells (median purity 71.9%). Negative depletion of B-lineage cells reduced the number of CD34+ cells to 33.3% of the baseline value (median purity 72.7%). However, long-term culture assays showed the recovery of >60% of primitive haemopoietic progenitor cells after depletion of the B-lineage-positive cells. All evaluable patients had detectable disease in PBSC collections. The first step of positive selection of CD34+ cells resulted in >2 logs of tumour cell purging. However, molecular assessment showed the persistence of the disease in 6/7 cases. Immunofluorescence analysis demonstrated 1 additional log of B-cell purging by negative depletion. More importantly, molecular evaluation of IgH CDRIII region showed the disappearance of myeloma cells in 6/7 patients. 12 patients received a median of 3.9 x 106 CD34+ B-lin- cells/kg after conditioning with high-dose melphalan and showed a rapid reconstitution of haemopoiesis. These results were similar to two similar cohorts of patients who received either unmanipulated PBSC or positively selected CD34+ cells after the same conditioning regimen. Severe extrahaematological toxicity was limited to mucositis; no late infections were observed. We concluded that autotransplantation of purified CD34+ B-lin- cells was associated with a rapid and sustained recovery of haemopoiesis and low peritransplant morbidity. Sequential positive and negative enrichment of stem cells reduced tumour cell contamination in B-cell malignancies below the lower limit of detection of molecular analysis.

Adolescent↗
PubMed2003

Identification of reproductively isolated lineages of Amur grayling (Thymallus grubii Dybowski 1869): concordance between phenotypic and genetic variation.

We analysed variation at maternally (mitochondrial DNA control region sequences) and bi-parentally (10 microsatellites) inherited genetic markers, as well as across 12 meristic characters in 7 populations of Amur grayling, Thymallus grubii, from eastern Siberia. All three data sets were concordant in supporting the existence of three diagnosable, reciprocally monophyletic, and most probably reproductively isolated, lineages of grayling within the Amur drainage. There was a significant correlation between genetic and phenotypic divergence, both within and among lineages. Two phenotypically distinct forms (with and without an orange spot on the posterior portion of the dorsal fin), found in sympatry in the lower Amur, most likely result from secondary contact, as they demonstrate 4.6% sequence divergence at the mitochondrial DNA control region. This divergence, together with the existence of at least one nearby population of orange spot grayling outside the Amur drainage (0.8% divergence) underscore the palaeo-hydrological complexity of the system, which presumably promoted genetic divergence in a shifting allopatric framework throughout the Pleistocene. Grayling from the upper Amur, corresponding to the type locality for the species, formed a sister group (1.4-1.6% divergent) to the orange spot lineage perhaps diverging in the early Pleistocene (1.4-1.6 Ma).

Alleles↗
PubMed2003

Ecological and morphological differentiation among cryptic evolutionary lineages in freshwater limpets of the nominal form-group Ancylus fluviatilis (O.F. Müller, 1774).

The phylogeny and potential mode of speciation of the river limpet Ancylus fluviatilis (Basommatophora) was examined using mitochondrial DNA sequences from 16S ribosomal RNA, cytochrome c oxidase subunit I (COI) and nuclear DNA from internal transcribed spacer (ITS-1) regions from 103 populations across Europe. Four highly divergent lineages were observed within Ancylus. Clade 1, representing the nominal taxon Ancylus fluviatilis (O.F. Müller, 1774), is mainly found in central and northern Europe, Clade 2 is present in a single Portuguese population, Clade 3 is distributed on the Canary islands, North Africa and the eastern Mediterranean region, whereas Clade 4 inhabits the Northern Mediterranean coasts. Phylogenetic analyses revealed an overall consistent topology of nuclear and mitochondrial gene trees. Based on a molecular clock, we estimated that the basic radiation occurred in the late Pliocene. Although clades differ significantly in size independent shell shape, morphological differentiation of lineages is not feasible without genetic data. Environmental data related to climate (precipitation, temperature, etc.) showed a significant differentiation of clades. Clade 1 dwells in relatively colder and more stable habitats than Clades 3 and 4, whose habitats in turn differ in a low or high amount of precipitation during spring and autumn, respectively. Based on the combined data sets on mitochondrial DNA, nuclear DNA, morphological and ecological differentiation, we conclude that Ancylus represents a cryptic species complex of reproductively and genetically isolated lineages. In addition, the joint analysis suggests that ecological speciation is probable to explain current patterns.

Analysis of Variance↗
PubMed2004

Fine-scale diversity and specificity in the most prevalent lineage of symbiotic dinoflagellates (Symbiodinium, Dinophyceae) of the Caribbean.

The success of coral reefs is due to obligate mutualistic symbioses involving invertebrates and photosynthetic dinoflagellate symbionts belonging to the genus Symbiodinium. In the Caribbean, the vast majority of octocorals and other invertebrate hosts associate with Symbiodinium clade B, and more selectively, with a single lineage of this clade, Symbiodinium B1/B184. Although B1/B184 represents the most prevalent Symbiodinium in the Caribbean, there is little evidence supporting fine-scale diversity and host-alga specificity within this lineage. We explored simultaneously the questions of diversity and specificity in Symbiodinium B1/B184 by sequencing the flanking regions of two polymorphic microsatellites from a series of Symbiodinium clade B cultures along with Symbiodinium B1/B184 populations of the octocorals Pseudopterogorgia elisabethae, P. bipinnata and Gorgonia ventalina. Seven unique sequence variants were identified based on concatenation of the two loci. Phylogenetic analyses of these variants, which we refer to as phylotypes, recognized five as belonging to B1/B184, thus providing the first evidence of distinct taxa within this Symbiodinium lineage. Furthermore, sympatric P. elisabethae and P. bipinnata at San Salvador in the Bahamas were found to harbour distinct Symbiodinium B1/B184 phylotypes, demonstrating unequivocally the existence of fine-scale specificity between Caribbean octocorals and these algae. Taken together, this study exemplifies the complex nature of Symbiodinium biodiversity and specificity.

Animals↗
PubMed2004

Design of 16S rRNA-targeted oligonucleotide probes for detecting cultured and uncultured archaeal lineages in high-temperature environments.

In order to facilitate the evaluation of archaeal community diversity and distribution in high-temperature environments, 14 16S rRNA oligonucleotide probes were designed. Adequate hybridization and wash conditions of the probes encompassing most known hyperthermophilic Archaea, members of the orders Thermococcales, Desulfurococcales and Sulfolobales, of the families Methanocaldococcaceae, Pyrodictiaceae and Thermoproteaceae, of the genera Archaeoglobus, Methanopyrus and Ignicoccus, and of the as yet uncultured lineages Korarchaeota, Crenarchaeota marine group I, deep-sea hydrothermal vent euryarchaeotic group 2 (DHVE 2), and deep-sea hydrothermal vent euryarchaeotic group 8 (DHVE 8) were determined by dot-blot hybridization from target and non-target reference organisms and environmental clones. The oligonucleotide probes were also used to evaluate the archaeal community composition in nine deep-sea hydrothermal vent samples. All probes, except those targeting members of Sulfolobales, Thermoproteaceae, Pyrodictiaceae and Korarchaeota, gave positive hybridization signals when hybridized against 16S rDNA amplification products obtained from hydrothermal DNA extracts. The results confirmed the widespread occurrence of Thermococcales, Desulfurococcales, Methanocaldococcaceae and Archaeoglobus in deep-sea hydrothermal vents, and extended the known ecological habitats of uncultured lineages. Despite their wide coverage, the probes were unable to resolve the archaeal communities associated with hydrothermally influenced sediments, suggesting that these samples may contain novel lineages. This suite of oligonucleotide probes may represent an efficient tool for rapid qualitative and quantitative characterization of archaeal communities. Their application would help to provide new insights in the future into the composition, distribution and abundance of Archaea in high-temperature environments.

Archaea↗
PubMed1999

An Asian-Native American paternal lineage identified by RPS4Y resequencing and by microsatellite haplotyping.

Human paternal population history was studied in 9 populations [three Native American, three Asian, two Caucasian and one African-derived sample(s)] using sequence and short tandem repeat haplotype diversity within the non-pseudoautosegmal region of the Y chromosome. Complete coding and additional flanking sequences (949 base pairs) of the RPS4Y locus were determined in 59 individuals from three of the populations, revealing a nucleotide diversity of 0.0147%, consistent with previous estimates from Y chromosome resequencing studies. One RPS4Y sequence variant, 711C > T, was polymorphic in Asian and Native American populations, but not in African and Caucasian population samples. The RPS4Y 711C > T variant, a second unique sequence variant at DYS287 and nine Y chromosome short tandem repeat (YSTR) loci were used to analyze the evolution of Y chromosome lineages. Three unambiguous lineages were defined in Asian, Native American and Jamaican populations using sequence variants at RPS4Y and DYS287. These lineages were independently supported by the haplotypes defined solely by YSTR alleles, demonstrating the haplotypes constructed from YSTRs can evaluate population diversity, admixture and phylogeny.

Alleles↗
PubMed2003

A predominant European ancestry of paternal lineages from Canary Islanders.

We genotyped 24 biallelic sites and 5 microsatellites from the non-recombining portion of the Y chromosome in 652 males from the Canary Islands. The results indicate that, contrary to mtDNA data, paternal lineages of the current population are overwhelmingly (>90%) of European origin, arguing for a highly asymmetric pattern of mating after European occupation. However, the presence of lineages of indisputable African assignation demonstrates that an aboriginal background still persists (<10%). On the basis of distribution and dating of some of these lineages we derived a genetic perspective of settlement processes of the archipelago in two stages, congruent with anthropological, archaeological and linguistic findings.

Africa↗
PubMed1995

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors mediate excitotoxicity in the oligodendroglial lineage.

We demonstrate by reverse transcriptase-polymerase chain reaction and Southern blotting that an immortalized rat oligodendroglial cell line (CG-4) expresses the non-N-methyl-D-aspartate (non-NMDA) glutamate receptor (GluR) genes GluR2-7, KA-1, and KA-2 and that nonimmortalized cells of the rat oligodendroglial lineage express the GluR1-3, GluR5-7, KA-1, and KA-2 genes. Lactic dehydrogenase release assays show that both immortalized and nonimmortalized cells of the oligodendroglial lineage are damaged by a 24-h exposure to 500 microM kainate or 5 mM L-glutamate, but not by a 24-h exposure to up to 10 mM alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA). Damage is prevented by the non-NMDA GluR channel inhibitor 6-cyano-7-nitroquinoxaline-2,3-dione and is also averted if Ca2+ is removed from the culture medium. Cyclothiazide, which blocks desensitization of AMPA-preferring GluRs, increases cytotoxicity of kainate as well as inducing toxicity of AMPA. We conclude that cells of the oligodendroglial lineage express a population of AMPA-preferring and possibly also kainate-preferring GluR channels that are capable of mediating Ca(2+)-dependent excitotoxicity and that AMPA-induced cytotoxicity is blocked by desensitization of AMPA-preferring GluRs.

Animals↗
PubMed2000

Utility of immunohistochemistry in bone marrow evaluation of T-lineage large granular lymphocyte leukemia.

Although T-lineage large granular lymphocyte (LGL) leukemia has been described for over 20 years, many patients with this neoplasm go unrecognized. Chief among the difficulties in diagnosing this entity is that the morphologic features are nonspecific and that it is difficult to distinguish it from reactive processes. The purpose of this study was to examine the histologic and immunophenotypic appearance of T-LGL leukemia in the peripheral blood and bone marrow, and to determine what features may suggest that ancillary studies such as flow cytometric and molecular analysis should be pursued to make a definitive diagnosis. We took a multidisciplinary approach by using morphology, immunoperoxidase staining, flow cytometric analysis, and molecular studies on 9 cases of T-lineage LGL leukemia. Our findings indicate that T-lineage LGL leukemia typically infiltrates the marrow diffusely. Most cases show a hypercellular marrow with an increase in myeloid precursors relative to the mature cells (i.e., an inversion of the myeloid maturation pyramid) and a decreased myeloid:erythroid ratio. Neutropenia without a left shift is usually seen in the peripheral blood. The tumor cells are usually CD3+, CD8+, CD57+, and TIA-1+. Most notably, the number of CD3+ T cells per high-power field is markedly elevated in T-LGL leukemia compared with normal, reactive, and pathologic marrows with neutropenia (mean values, 559 cells/mm(2) v. 7/mm(2), 11/mm(2), and 263/mm(2), respectively, P<.01). Moreover, CD57 staining also shows an increase in positive cells in T-LGL cases in comparison with normal, reactive, and pathologic marrows with neutropenia. Taken together, these findings indicate immunoperoxidase findings may be a useful tool to identify cases that should proceed to molecular or flow cytometric analysis.

Aged↗
PubMed1984

Volume regulation in lymphoid leukemia cells and assignment of cell lineage.

Normal T lymphocytes readjust their volume after swelling in hypotonic medium, whereas B lymphocytes remain swollen. The difference between the two cell types appears to lie in the inability of B cells to increase their permeability to potassium in response to swelling. We have studied mononuclear cells from the bone marrow of 65 patients with lymphocytic leukemia, to determine whether the response to a hypotonic environment could be used to assign cell lineage. In contrast to leukemic cells of B-cell lineage (as in B-cell acute or chronic lymphocytic leukemia and non-T-cell, non-B-cell acute lymphocytic leukemia), T-cell-leukemia cells responded within five minutes to hypotonic swelling with an increase in potassium permeability and restoration toward isotonic volume. We conclude that the response to hypotonic shock may distinguish leukemic cells of T-cell origin from those derived from B-cell precursors and provides a simple, rapid, and reliable means for assigning cell lineage to lymphoid leukemia cells.

B-Lymphocytes↗
PubMed2002

Rate heterogeneity among lineages of tracheophytes: integration of molecular and fossil data and evidence for molecular living fossils.

Many efforts to date evolutionary divergences by using a molecular clock have yielded age estimates that are grossly inconsistent with the paleontological evidence. Such discrepancies often are attributed to the inadequacy of the fossil record, but many potential sources of error can affect molecular-based estimates. In this study, we minimize the potential error caused by inaccurate topology and uncertain calibration times by using a well-supported tree, multiple genes, and multiple well-substantiated dates to explore the correspondence between the fossil record and molecular-based age estimates for major clades of tracheophytes. Age estimates varied because of gene effects, codon position, lineage effects, method of inferring branch lengths, and whether or not rate constancy was assumed. However, even methods designed to ameliorate the effects of rate heterogeneity among lineages could not accommodate the substantially slower rates observed in Marattia + Angiopteris and in the tree ferns. Both of these clades of ferns have undergone dramatic decelerations in their rates of molecular evolution and are "molecular living fossils," consistent with their relative morphological stasis for the past 165-200 million years. Similar discrepancies between the fossil record and molecular-based age estimates noted in other studies may also be explained in part by violations of rate constancy among lineages.

Journal Article↗