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PubMed2006

An equivalence principle for the incorporation of favorable mutations in asexual populations.

Rapid evolution of asexual populations, such as that of cancer cells or of microorganisms developing drug resistance, can include the simultaneous spread of distinct beneficial mutations. We demonstrate that evolution in such cases is driven by the fitness effects and appearance times of only a small minority of favorable mutations. The complexity of the mutation-selection process is thereby greatly reduced, and much of the evolutionary dynamics can be encapsulated in two parameters-an effective selection coefficient and effective rate of beneficial mutations. We confirm this theoretical finding and estimate the effective parameters for evolving populations of fluorescently labeled Escherichia coli. The effective parameters constitute a simple description and provide a natural standard for comparing adaptation between species and across environments.

Adaptation, Biological↗
PubMed1985

Pefloxacin: evolution of in vitro activity during 18 months of use in an intensive care unit.

The MIC of pefloxacin against all the strains (3122) isolated in an intensive care unit during 18 months was studied. The MIC of pefloxacin was estimated by standard agar diffusion method in Mueller-Hinton agar. All the strains with a MIC lower than 2 mg/l were considered as sensitive, between 2 and 4 mg/l as "intermediary" and over 4 mg/l as resistant. Geometrical means of MICs were calculated for each month and for different species. The study continued for 18 months from the introduction of the drug which was in widespread and constant use as a first-choice antibiotic. No significant increase was detected in the incidence of resistant strains during the study; on the other hand, small, limited clusters of resistant strains were observed during minor nosocomial epidemics. The general features of quinolone activity, the spectrum of this new quinolone and the slow evolution of the bacterial population are discussed.

Bacteria, Aerobic↗
PubMed2005

Caste evolution and ecology: a special worker for novel prey.

Individual specialization underpins the division of labour within ant societies, but only in a small minority do morphological specialists, or physical castes, exist in the workforce. The genetic conditions that allow such castes to evolve are well understood, but the ecological pressures that select for them are not. We provide compelling evidence that the task of transporting novel prey selected for an exaggerated transport caste, or 'submajor', in the army ant Eciton burchellii. This species is the only Eciton that preys upon large arthropods as well as ants, the ancestral prey type, and by comparing load-transport among Eciton species and within E. burchellii, we show that this mixed diet significantly constrains transport efficiency. Crucially, however, we also show that E. burchellii submajors are highly specialized on transporting non-ant prey, and we demonstrate experientially that it is specifically this prey type that constrains prey-transport efficiency. Our study also suggests that phylogenetic constraints associated with the Eciton lifestyle intensified selection for the exaggerated submajor of E. burchellii. Thus, we propose that a novel task may only select for a special caste when phylogenetic constraints preclude the evolution of alternative solutions. This identifies a new and potentially general scenario for the evolution of physical castes.

Analysis of Variance↗
PubMed1998

Evolution of repetitive proteins: spider silks from Nephila clavipes (Tetragnathidae) and Araneus bicentenarius (Araneidae).

Spider silks are highly repetitive proteins, characterized by regions of polyalanine and glycine-rich repeating units. We have obtained two variants of the Spidroin 1 (NCF-1) silk gene sequence from Nephila clavipes. One sequence (1726 bp) was from a cloned cDNA, and the other (1951 bp) was from PCR of genomic DNA. When these sequences are compared with each other and the previously published Spidroin 1 sequence, there are differences due to sequence rearrangements, as well as single base substitutions. These variations are similar to those that have been reported from other highly repetitive genes, and probably represent the results of unequal cross-overs. We have also obtained 708 bp of sequence from pCR of genomic DNA from Araneus biocentenarius. This sequence shows considerable similarity to a dragline sequence (ADF-3) from A. diadematus, as well as Spidroin 2 (NCF-2) from N. clavipes. Minor but consistent differences in the repeating unit sequence between A. bicentenarius and A. diadematus suggest that concerted evolution or gene conversion processes are acting to maintain similarity among repeat units within a single gene.

Amino Acid Sequence↗
PubMed1993

The genetic origin of minor histocompatibility antigens.

The purpose of this study was to elucidate the genetic origin of minor histocompatibility (H) antigens. Toward this end common inbred mouse strains, distinct subspecies, and species of the subgenus Mus were examined for expression of various minor H antigens. These antigens were encoded by the classical minor H loci H-3 and H-4 or by newly identified minor H antigens detected as a consequence of mutation. Both minor H antigens that stimulate MHC class I-restricted cytotoxic T cells (Tc) and antigens that stimulate MHC class II-restricted helper T cells (Th) were monitored. The results suggested that strains of distinct ancestry commonly express identical or cross-reactive antigens. Moreover, a correlation between the lack of expression of minor H antigens and ancestral heritage was observed. To address whether the antigens found on unrelated strains were allelic with the sensitizing minor H antigens or a consequence of antigen cross-reactivity, classical genetic segregation analysis was carried out. Even in distinct subspecies and species, the minor H antigens always mapped to the site of the appropriate minor H locus. Together the results suggest: 1) minor H antigen sequences are evolutionarily stable in that their pace of antigenic change is slow enough to predate subspeciation and speciation; 2) the minor H antigens originated in the inbred strains as a consequence of a rare polymorphism or loss mutation carried in a founder mouse stock that caused the mouse to perceive the wild-type protein as foreign; 3) there is a remarkable lack of antigenic cross-reactivity between the defined minor H antigens and other gene products.

Animals↗
PubMed2005

Back to the future: genetic correlations, adaptation and speciation.

Genetic correlations can affect the course of phenotypic evolution. Although genetic correlations among traits are a common feature of quantitative genetic analyses, they have played a very minor role in recent linkage-map based analyses of the genetic architecture of quantitative traits. Here, we use our work on host-associated races in pea aphids to illustrate how quantitative trait locus (QTL) mapping can be used to test specific hypotheses about how genetic correlations may facilitate ecological specialization and speciation.

Adaptation, Biological↗
PubMed1997

Molecular variation, evolution and geographical distribution of louping ill virus.

Following the demonstration that the tick-borne encephalitis (TBE) subgroup viruses are distributed as a cline across the Northern Hemisphere (Zanotto et al., 1995), we have analyzed the dispersal pattern of louping ill (LI) virus, the most westerly located member in the cline. A total number of 21 LI or LI-related virus E gene sequences have been used for a detailed molecular analysis of the evolution, phylogeny and geographical distribution of LI virus in the British Isles and Ireland. The results show that LI virus is genetically stable in general but minor differences enable its separation into four genetically distinct subtypes (genotypes) with clear geographical correlation, designated Type 1 in Scotland and England, Type 2 in Scotland, Type 3 in Wales and Type 4 in Ireland. These data demonstrate that geographically independent evolution of LI viruses has occurred. The molecular systematics and substitutional parameters analyses combined with the clinal distribution of the TBE virus complex allow the assignment of the origin for both Negishi (NEG) virus and a Norwegian isolate to the British Isles. Moreover, proposals for the classification of LI and LI-like viruses which cause encephalomyelitis in sheep, goat or cattle are presented.

Animals↗
PubMed1983

[Demonstration of an original process of asexual reproduction in Schistosoma haematobium].

The study of development of a Malagash strain of Schistosoma haematobium in Bulinus obtusispira reveals two original processes in asexual reproduction: (a) The existence of an evolutive dimorphism of the secondary sporocysts: - an important secondary sporocyst population, localized mainly in the foot, produces daughter sporocysts (order III); - a minor secondary sporocyst population, localized mainly in the digestive gland, produces cercariae. (b) A part of secondary sporocysts which, after leaving the primary sporocyst, does not migrate but develops in the foot of the snail.

Animals↗
PubMed2000

Terrestrial planet and asteroid formation in the presence of giant planets. I. Relative velocities of planetesimals subject to Jupiter and Saturn perturbations.

We investigate the orbital evolution of 10(13)- to 10(25) -g planetesimals near 1 AU and in the asteroid belt (near 2.6 AU) prior to the stage of evolution when the mutual perturbations between the planetesimals become important. We include nebular gas drag and the effects of Jupiter and Saturn at their present masses and in their present orbits. Gas drag introduces a size-dependent phasing of the secular perturbations, which leads to a pronounced dip in encounter velocities (Venc) between bodies of similar mass. Plantesimals of identical mass have Venc approximately 1 and approximately 10 m s-1 (near 1 and 2.6 AU, respectively) while bodies differing by approximately 10 in mass have Venc approximately 10 and approximately 100 m s-1 (near 1 and 2.6 AU, respectively). Under these conditions, growth, rather than erosion, will occur only by collisions of bodies of nearly the same mass. There will be essentially no gravitational focusing between bodies less than 10(22) to 10(25) g, allowing growth of planetary embryos in the terrestrial planet region to proceed in a slower nonrunaway fashion. The environment in the asteroid belt will be even more forbidding and it is uncertain whether even the severely depleted present asteroid belt could form under these conditions. The perturbations of Jupiter and Saturn are quite sensitive to their semi-major axes and decrease when the planets' heliocentric distances are increased to allow for protoplanet migration. It is possible, though not clearly demonstrated, that this could produce a depleted asteroid belt but permit formation of a system of terrestrial planet embryos on a approximately 10(6)-year timescale, initially by nonrunaway growth and transitioning to runaway growth after approximately 10(5) years. The calculations reported here are valid under the condition that the relative velocities of the bodies are determined only by Jupiter and Saturn perturbations and by gas drag, with no mutual perturbations between planetesimals. If, while subject to these conditions, the bodies become large enough for their mutual perturbations to influence their velocity and size evolution significantly, the problem becomes much more complex. This problem is under investigation.

Astronomical Phenomena↗
PubMed1987

Numerical simulations and the problem of periodicity in the cratering record.

Ages of craters in the record of impacts on earth may be uniformly period, totally random, or a mixture of the two. These alternatives are studied through numerical simulation wherein time-series analysis is performed on real and simulated sequences to which random noise has been added to represent age-dating uncertainty. We conclude that the real record is most likely to have been generated by a mixture of random and periodic impacts, with the random events constituting the majority.

Biological Evolution↗
PubMed1999

Detection and quantitation of genetically marked acute myeloid leukemia by competitive polymerase chain reaction after autologous bone marrow transplantation: a preclinical model for minimal residual disease.

Preclinical models and methods aimed at detecting and quantitating minimal residual disease (MRD) after autologous bone marrow transplantation (BMT) for acute myeloid leukemia (AML) could facilitate assessment of innovative therapeutic strategies for their antileukemic potential. Among the various techniques exploited to identify MRD, polymerase chain reaction (PCR) proved to be a valuable tool in instances in which clonogeneic markers are involved during the evolution of disease. In human AML, however, detection of MRD by PCR is limited to a minority of subgroups, as clonospecific markers are absent or presently unknown. Although gene labeling has proved to be efficient in detecting marker-devoid leukemia cells in preclinical models, detection and quantitation by PCR have not yet been considered. We therefore developed an experimental model in which detection and quantitation of genetically marked murine AML cells are based on a highly sensitive two-step nested PCR and competitive PCR protocol, respectively. We further demonstrated its applicability to a murine syngeneic BMT model that was designed to monitor minimal numbers of gene-tagged AML cells at various time intervals after transplantation. Our results showed that detection and quantitation could reproducibly be achieved at levels as low as one in 10(6) and 10(5) cells, respectively.

Acute Disease↗
PubMed1989

Pre-biotic organic matter from comets and asteroids.

Several authors have suggested that comets or carbonaceous asteroids contributed large amounts of organic matter to the primitive Earth, and thus possibly played a vital role in the origin of life. But organic matter cannot survive the extremely high temperatures (>10(4) K) reached on impact, which atomize the projectile and break all chemical bonds. Only fragments small enough to be gently decelerated by the atmosphere--principally meteors of 10(-12)-10(-6) g--can deliver their organic matter intact. The amount of such 'soft-landed' organic carbon can be estimated from data for the infall rate of meteoritic matter. At present rates, only approximately 0.006 g cm-2 intact organic carbon would accumulate in 10(8) yr, but at the higher rates of approximately 4 x 10(9) yr ago, about 20 g cm-2 may have accumulated in the few hundred million years between the last cataclysmic impact and the beginning of life. It may have included some biologically important compounds that did not form by abiotic synthesis on Earth.

Atmosphere↗
PubMed2001

Heterogeneity of VH-JH gene rearrangement patterns: an insight into the biology of B cell precursor ALL.

Oligoclonal B cell proliferation, as defined by the presence of more than one leukemic clone, has been detected in approximately 20% to 30% of patients with acute lymphoblastic leukemia (ALL) using PCR or Southern blotting. An accurate assessment of these populations is required to avoid false negative measurements of minimal residual disease (MRD) in follow-up bone marrow (BM) samples of ALL patients. In this study, we analysed 29 ALL patients with two or more immunoglobulin heavy (IGH) chain gene rearrangements in the presentation samples using IGH fingerprinting PCR and sequence analysis. Thirty-nine (51%) of 76 sequences (from 15 patients), shared no VNDNJ homology (ie different CDR3 regions). In the remaining 14 patients, at least two related VH sequences were identified in each patient (identical DNJ sequences). Numerical abnormalities of chromosome 14 was detected in 10 patients. Eight patients were analysed at presentation and relapse. In four of them, expansion of a minor presentation-clone was detected at relapse while the major presentation clone disappeared, confirming 'subclonal evolution'. Finally, in our cohort of patients, the presence of related or unrelated IGH clones did not influence overall survival.

Adolescent↗
PubMed1999

The stabilized structural array of two HMG1/2-boxes endowed by a linker sequence between them is requisite for the effective binding of HMG1 with DNA.

High mobility group (HMG) protein 1 contains two DNA binding motifs, called HMG1/2-boxes, linked with a linker region. The functional relationships between the two boxes and the mechanism of involvement of the linker region for effective binding of HMG1 were examined. The binding analyses of truncated HMG1 peptides with DNA indicated that the structural array of two boxes stabilizes the interaction of HMG1 with DNA. The mutation analyses of the linker region suggested that the region is equipped with tolerance for the deletion of a few amino acid residues to allow appropriate binding of the two boxes with DNA, and that the basic cluster in the linker sequence is in a position to interact with DNA. The existence of tolerance for the linker sequence was found to be conserved during the evolution of HMG1 protein homologues. A structural model for array of two boxes associating with DNA minor groove was constructed on the basis of the experimental results and energy minimization. The model proposes that the DNA binding region in HMG1 covers an 18 bp DNA region and induces its bending by about 140 degrees. The linker region may function to maintain the structural array of two HMG1/2-boxes by direct interaction with DNA.

Amino Acid Sequence↗
PubMed1991

Different patterns of pulmonary sequelae after hyaline membrane disease: heterogeneity of bronchopulmonary dysplasia? A clinicopathologic study.

In an autopsy study of 37 infants who suffered from hyaline membrane disease (HMD), two distinct patterns of pulmonary lesions could be defined. One pattern, characterized by marked interstitial fibrosis in the absence of airway abnormalities, was labelled 'interstitial-type' histology. A second type, labelled 'bronchiolar-type' histology, showed marked airway lesions and alveolar emphysema. Nine patients of each type were analysed. Nineteen other patients had a 'mixed-type' histology and were not further studied. Retrospectively, the clinical and radiological characteristics of both series were analysed. No differences in birth weight, gestational age and initial radiological HMD grade could be demonstrated. The pulmonary function of the bronchiolar-type patients however was significantly worse at the onset, and these infants needed more oxygen and ventilatory support during the first 10 days of life. They all died from respiratory failure whereas 4 patients from the interstitial group had non-pulmonary fatalities. In the bronchiolar group chest X-rays showed atelectasis and pulmonary interstitial emphysema in the early stages, and hyperinflation with bullae and irregular streaky densities in the later. Patients in the interstitial group had no or minor emphysema with more homogeneously spread densities over both lungs. We conclude that both types of evolution represent two extremes of the bronchopulmonary dysplasia spectrum.

Bronchopulmonary Dysplasia↗
PubMed2000

Large deletions at the t(9;22) breakpoint are common and may identify a poor-prognosis subgroup of patients with chronic myeloid leukemia.

The hallmark of chronic myeloid leukemia (CML) is the BCR-ABL fusion gene, which is usually formed as a result of the t(9;22) translocation. Patients with CML show considerable heterogeneity both in their presenting clinical features and in the time taken for evolution to blast crisis. In this study, metaphase fluorescence in situ hybridization showed that a substantial minority of patients with CML had large deletions adjacent to the translocation breakpoint on the derivative 9 chromosome, on the additional partner chromosome in variant translocations, or on both. The deletions spanned up to several megabases, had variable breakpoints, and could be detected by microsatellite polymerase chain reaction in unfractionated bone marrow and purified peripheral blood granulocytes. The deletions were likely to occur early and possibly at the time of the Philadelphia (Ph) chromosome translocation: deletions were detected at diagnosis in 11 patients, were found in all Ph-positive metaphases, and were more prevalent in patients with variant Ph chromosomes. Kaplan-Meier analysis showed a median survival time of 36 months in patients with a deletion; patients without a detectable deletion survived > 90 months. The survival-time difference was significant on log-rank analysis (P =. 006). Multivariate analysis demonstrated that the prognostic importance of deletion status was independent of age, sex, percentage of peripheral blood blasts, and platelet count. Our data therefore suggest that an apparently simple, balanced translocation may result not only in the generation of a dominantly acting fusion oncogene but also in the loss of one or more genes that influence disease progression. (Blood. 2000;95:738-743)

Adolescent↗