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PubMed2025

Long-read sequencing of single cell-derived melanoma subclones reveals divergent and parallel genomic and epigenomic evolutionary trajectories.

Tumor evolution is driven by various mutational processes, ranging from single-nucleotide variants (SNVs) to large structural variants (SVs) to dynamic shifts in DNA methylation. Current short-read sequencing methods struggle to accurately capture the full spectrum of these genomic and epigenomic alterations due to inherent technical limitations. To overcome that, here we introduce an approach for long-read sequencing of single-cell derived subclones, and use it to profile 23 subclones of a mouse melanoma cell line, characterized with distinct growth phenotypes and treatment responses. We develop a computational framework for harmonization and joint analysis of different variant types in the evolutionary context. Uniquely, our framework enables detection of recurrent amplifications of putative driver genes, generated by independent SVs across different lineages, suggesting parallel evolution. In addition, our approach revealed gradual and lineage-specific methylation changes associated with aggressive clonal phenotypes. We also show our set of phylogeny-constrained variant calls along with openly released sequencing data can be a valuable resource for the development of new computational methods.

Journal Article↗
PubMed2003

P systems with deadlock.

Rewriting P systems with parallel application of evolution rules, as defined in Besozzi et al. [Parallel rewriting P systems with deadlock. In: Hagiya, M., Ohuchi, A. (Eds.), Pre-Proceedings of DNA8 Conference, Hokkaido University, Japan, June 2002a, pp. 171-183], are considered here. Different kinds of parallelism methods are defined for string rewriting. The notion of deadlock is then introduced to describe situations where rules with mixed target indications are simultaneously applied to a common string. The generative power of parallel P systems with deadlock is analyzed, with respect to Lindenmayer systems, and some relations among different types of parallel P systems with or without deadlock, allowing to rewrite all occurrences of a single symbol, or all the symbols applying either any of the rules or only those belonging to a specific set (table) of rules are studied. Some open problems are also formulated.

Algorithms↗
PubMed2002

Mitochondrial DNA variability in Poles and Russians.

Mitochondrial DNA (mtDNA) sequence variation was examined in Poles (from the Pomerania-Kujawy region; n = 436) and Russians (from three different regions of the European part of Russia; n = 201), for which the two hypervariable segments (HVS I and HVS II) and haplogroup-specific coding region sites were analyzed. The use of mtDNA coding region RFLP analysis made it possible to distinguish parallel mutations that occurred at particular sites in the HVS I and II regions during mtDNA evolution. In total, parallel mutations were identified at 73 nucleotide sites in HVS I (17.8%) and 31 sites in HVS II (7.73%). The classification of mitochondrial haplotypes revealed the presence of all major European haplogroups, which were characterized by similar patterns of distribution in Poles and Russians. An analysis of the distribution of the control region haplotypes did not reveal any specific combinations of unique mtDNA haplotypes and their subclusters that clearly distinguish both Poles and Russians from the neighbouring European populations. The only exception is a novel subcluster U4a within subhaplogroup U4, defined by a diagnostic mutation at nucleotide position 310 in HVS II. This subcluster was found in common predominantly between Poles and Russians (at a frequency of 2.3% and 2.0%, respectively) and may therefore have a central-eastern European origin.

DNA, Mitochondrial↗
PubMed1994

Evolution of homeotic gene regulation and function in flies and butterflies.

It has been proposed that the evolution of homeotic genes parallels, and to some degree directs, the evolution of segment diversity in the myriapod-insect lineage. But the discovery of discrete Antennapedia complex (ANT-C) and bithorax complex (BX-C) gene members in crustacea, chelicerates, annelids and various insects, as well as in vertebrates, indicates that the expansion and diversification of homeotic genes preceded the diversification of arthropods and insects. How, then, have these genes influenced the evolution of body plans? To address this question, we now examine homeotic gene expression and regulation in butterflies (Lepidoptera), which, unlike flies, possess larval abdominal limbs and two pairs of wings. We show that the difference in larval limb number between these insects results from striking changes in BX-C gene regulation in the butterfly abdomen, and we deduce that the wing-patterning genes regulated by Ultrabithorax have diverged in the course of butterfly and fly evolution. These findings have general implications for the role of homeotic genes in animal evolution.

Amino Acid Sequence↗
PubMed2025

Reproductive Isolation due to Divergent Ecological Selection Is Accompanied by Vast Genomic Instability in Experimentally Evolved Yeast Populations.

Populations evolving independently in divergent environments accumulate genetic differences and potentially evolve reproductive isolation as a by-product of divergence. The speed and mechanisms underlying this process are difficult to investigate because we rarely get the opportunity to witness them in natural settings, and histories of selection and gene flow between populations are often unknown. Here, we experimentally evolved yeast for 1000 generations of evolution in both divergent and parallel environments. At regular time points during experimental evolution, we made crosses between parallel- and divergent-evolving populations to measure postzygotic reproductive isolation (gamete viability). We used whole genome population sequencing to determine the mutational load, the number and types of structural variation, and other genomic features of the parent, F1 and F2 intraspecific hybrids. We found evidence for large-scale phenotypic and genome-wide differentiation in response to divergent laboratory selection. Divergent-selected populations produced hybrids with reduced gamete viability-a classic signature of postzygotic reproductive isolation in the form of hybrid breakdown. Parallel-selected populations, on the other hand, remained more reproductively compatible (with exceptions). We found that F2 hybrid genomes contained vast genomic instability, that is, new structural variants (especially insertions, deletions and interchromosomal translocations) that were not observed in parent and F1 genomes, which is likely a result of chromosome missegregation and recombination errors in hybrid meiosis. Our results provide phenotypic and genomic evidence that partial reproductive isolation evolved due to adaptation to divergent environments, consistent with predictions of ecological speciation theory.

Reproductive Isolation↗
PubMed1984

Meal to meal energy balance in rats.

Meal to meal energy balance was examined in thirty-eight simultaneous recordings of feeding pattern and O2 consumption in six rats. The mean difference between energy intake in a meal and energy expenditure until the onset of the next meal was found positive at night and negative during day time. At night the excess of meal intake over meal to meal expenditures was decreasing from the beginning to the end of the night and was strongly correlated to meal sizes. During day time meal to meal deficit was decreasing from the beginning to the end of the period but was not correlated to meal sizes. These meal location and size effects on the meal to meal energy balance were not determined by an effect of these factors on metabolic rate. No indication was provided that meal to meal energy balance was influenced by a "meal induced thermogenesis." Rather an evolution from the beginning to the end of the night of the correlation between meal size and durations of meal to meal intervals was found to be parallel to the evolution of positive meal to meal energy balance throughout the night. From these data it is concluded that at night a dual utilization of meal caloric intake (current energy metabolism plus fat storage) and a dual source of fuel during the day (food plus mobilized fats) determine time and mechanism of meal onset.

Animals↗
PubMedDate not supplied

[Aging and atherosclerosis of human aorta. Comparative evolution of seven glycosyl-transferases and of lactate-dehydrogenase (author's transl)].

Seven glycosyl-transferases and the lactico-dehydrogenase from human aortas were assayed. These aortas were divided in five classes according to the age and in five steps according to the atherogenesis. These enzymic activities do not show any parallelism in their evolution; their variation with age and with atherogenesis is quite different. For example, the N-acetylgalactosaminyl-transferase activity increases with atherogenesis whereas it diminishes with age; on the other hand the lactate-dehydrogenase activity increases with age and decreases with atherogenesis; the sialyl-transferase activity is nearly constant during adulthood while it hardly declines with atherogenesis. These assays suggest: 1) an effect of energy metabolism on the glycosyl-transferase activities; 2) a qualitative and quantitative variation of the glycosaminoglycans biosynthesis; 3) a structural modification of the glucidic part of the glycoproteins which can induce the formation of antigenic sites.

Adolescent↗
PubMed1998

Evolution of the cytochrome P450 superfamily: sequence alignments and pharmacogenetics.

The evolution of the cytochrome P450 (CYP) superfamily is described, with particular reference to major events in the development of biological forms during geological time. It is noted that the currently accepted timescale for the elaboration of the P450 phylogenetic tree exhibits close parallels with the evolution of terrestrial biota. Indeed, the present human P450 complement of xenobiotic-metabolizing enzymes may have originated from coevolutionary 'warfare' between plants and animals during the Devonian period about 400 million years ago. A number of key correspondences between the evolution of P450 system and the course of biological development over time, point to a mechanistic molecular biology of evolution which is consistent with a steady increase in atmospheric oxygenation beginning over 2000 million years ago, whereas dietary changes during more recent geological time may provide one possible explanation for certain species differences in metabolism. Alignment between P450 protein sequences within the same family or subfamily, together with across-family comparisons, aid the rationalization of drug metabolism specificities for different P450 isoforms, and can assist in an understanding of genetic polymorphisms in P450-mediated oxidations at the molecular level. Moreover, the variation in P450 regulatory mechanisms and inducibilities between different mammalian species are likely to have important implications for current procedures of chemical safety evaluation, which rely on pure genetic strains of laboratory bred rodents for the testing of compounds destined for human exposure.

Amino Acid Sequence↗
PubMedDate not supplied

[Sacrococcygeal teratoma in the adult].

Problems of diagnosis, classification, and histologic definition, as well as possibilities of evolution are discussed, of teratomas or of tumours resulting from the disturbed development of the sacro-coccygeal area, in connection with a case of recidivating sacro-coccygeal teratoma in a woman aged 40 years. The therapeutic principles are also discussed The risk of malignant degeneration of these lesions, in parallel with their evolution in time, make necessary surgical exeresis immediately after making the diagnosis. Surgery should be performed with a maximum amount of comfort, under general anesthesia, preferably in the Kraske position, in view of the complete extirpation of pathological tissues. Resection of the coccyx and of the last sacral vertebrae allows to widen the approach, facilitating the complete exeresis, and avoiding the two risks which are characteristic for this intervention: lesion of the rectum, and haemorrhage which is difficult to control. The postoperative aspiratory draining is useful for the favourable evolution of the wound.

Adult↗
PubMed2000

An ancestral MADS-box gene duplication occurred before the divergence of plants and animals.

Changes in genes encoding transcriptional regulators can alter development and are important components of the molecular mechanisms of morphological evolution. MADS-box genes encode transcriptional regulators of diverse and important biological functions. In plants, MADS-box genes regulate flower, fruit, leaf, and root development. Recent sequencing efforts in Arabidopsis have allowed a nearly complete sampling of the MADS-box gene family from a single plant, something that was lacking in previous phylogenetic studies. To test the long-suspected parallel between the evolution of the MADS-box gene family and the evolution of plant form, a polarized gene phylogeny is necessary. Here we suggest that a gene duplication ancestral to the divergence of plants and animals gave rise to two main lineages of MADS-box genes: TypeI and TypeII. We locate the root of the eukaryotic MADS-box gene family between these two lineages. A novel monophyletic group of plant MADS domains (AGL34 like) seems to be more closely related to previously identified animal SRF-like MADS domains to form TypeI lineage. Most other plant sequences form a clear monophyletic group with animal MEF2-like domains to form TypeII lineage. Only plant TypeII members have a K domain that is downstream of the MADS domain in most plant members previously identified. This suggests that the K domain evolved after the duplication that gave rise to the two lineages. Finally, a group of intermediate plant sequences could be the result of recombination events. These analyses may guide the search for MADS-box sequences in basal eukaryotes and the phylogenetic placement of new genes from other plant species.

Amino Acid Sequence↗
PubMed1999

Orthologs, paralogs and genome comparisons.

During the past decade, ancient gene duplications were recognized as one of the main forces in the generation of diverse gene families and the creation of new functional capabilities. New tools developed to search data banks for homologous sequences, and an increased availability of reliable three-dimensional structural information led to the recognition that proteins with diverse functions can belong to the same superfamily. Analyses of the evolution of these superfamilies promises to provide insights into early evolution but are complicated by several important evolutionary processes. Horizontal transfer of genes can lead to a vertical spread of innovations among organisms, therefore finding a certain property in some descendants of an ancestor does not guarantee that it was present in that ancestor. Complete or partial gene conversion between duplicated genes can yield phylogenetic trees with several, apparently independent gene duplications, suggesting an often surprising parallelism in the evolution of independent lineages. Additionally, the breakup of domains within a protein and the fusion of domains into multifunctional proteins makes the delineation of superfamilies a task that remains difficult to automate.

Animals↗
PubMed2026

Global lessons from antibiotic resistance: Metformin-hydrolysing genes in transposable elements, a new threat for type II diabetic patients?

OBJECTIVES: To investigate the evolutionary origin, genomic mobility, and potential dissemination of metformin-hydrolysing genes (mfmAB), and to assess whether environmental selection by metformin pollution may drive the emergence of transferable pharmaceutical-degrading traits analogous to antibiotic resistance. METHODS: Large-scale comparative genomics was performed using publicly available bacterial genomes carrying mfmAB homologs. Phylogenomic reconstruction, average nucleotide identity analysis, genomic context comparison, plasmid characterization, and insertion sequence mapping were used to infer evolutionary history and identify mechanisms of horizontal gene transfer. RESULTS: mfmAB homologs were identified in twelve Aminobacter and three Pseudomonas genomes within a conserved ∼8.2 kb gene cluster. Phylogenomic analyses showed that metformin-degrading capacity emerged independently in multiple Aminobacter lineages across distinct continents, consistent with convergent evolution under anthropogenic selective pressure. Genomic comparisons indicated a chromosomal origin of mfmAB, followed by mobilization onto conjugative plasmids through IS1182-mediated transposition. In Pseudomonas, additional IS3/IS6-mediated transposition events integrated mfmAB into diverse plasmid backbones, frequently within composite transposons also encoding guanylurea and biguanide degradation pathways (guuH, bguH). These findings reveal a dynamic modular assembly of metabolic functions facilitating adaptation to pharmaceutical pollutants. CONCLUSIONS: Metformin pollution appears to promote the emergence and mobilization of pharmaceutical-degrading genes through mechanisms paralleling antibiotic resistance evolution. Although no clinical impact has yet been demonstrated, the potential spread of such genes into human-associated microbiomes and their possible co-selection with antibiotic resistance determinants represent an emerging One Health concern. Environmental surveillance of pharmaceutical-degrading genes is warranted to anticipate future threats to drug efficacy.

Convergent evolution↗
PubMed1989

The evolution of complex sensory systems in mammals.

Much of the forebrain of many extant species of mammals appears to be sensory-perceptual in nature. Thus, much of the forebrain, especially the dorsal thalamus and neocortex, consists of nuclei and areas that are parts of complex systems that analyze sensory information and allow behavior to be guided by accurate inferences about the external world. Since mammals vary tremendously in brain size, they vary in the amount of tissue devoted to sensory processing. In addition, mammals vary in the sizes and numbers of processing nuclei and areas, and in how neurons and neuron groups (modules) are differentiated within such structures. Sensory-perceptual systems with more, larger and more differentiated parts may allow more stimulus parameters to be considered, experience to play a greater role, and speed calculations through increased parallel processing. The evolution of species differences in brain size, the sizes of individual parts, and internal structure of these parts are potentially understandable within a theoretical framework of gradual modifications of developmental processes. In addition to changes in the generation and specialization of neurons, alterations in the developmental timing that modify internal and external influences on neuron activity patterns seem to have a major role in the construction and maintenance of organization in the nervous system. Because similar selection pressures may arise over and over again and the mechanisms for producing changes may be few, similar changes in the nervous system are likely to occur in independent lines of evolution. It is uncertain how new cortical areas and nuclei evolve. Comparative studies suggest that: (1) all mammals have a few basic sensory areas and nuclei in common, (2) the number of areas and nuclei has increased independently in several lines of mammalian evolution, and (3) new areas have been added to the middle levels of cortical processing sequences. New areas and nuclei may have evolved as a result of sudden duplications and/or by the process of single areas or nuclei gradually differentiating into two or more areas or nuclei. The process of gradual differentiation may have involved the initial step of differentiating functionally distinct classes of cells that are mixed in a representation, followed by the local groupings of such cells into functionally distinct sets, and finally the fusion of cell groups of the same types to form separate representations.

Afferent Pathways↗
PubMedDate not supplied

[Correlation between E.N.G. changes and the evolution of the hematic constants in patients under prolonged hemodialysis and renal transplantation].

An evolutive study of the E.N.G. on 25 patients affected of chronic renal failure (c.r.f.) in their previous periods and during the dialysis programme was developed. At the same time a large study on various serum changes was carried on. It is observed that the motor conduction velocity (M.C.V.) shows a decreasing evolution during dialysis, which mathematical patters is a branch of an equilateral hyperbola, of equation: (see article) The Na and K evolutive curves are also significatively fitted to the same mathematical pattern. It is observed a direct and inverse lineal correlation between M.C.V. values and those ones of the Na and K respectively, with p less than 0,05 and p less than 0,01. It is not observed any correlation of significatively value with the other serum parameters studied (R.A., Cl, Urea, Total proteins, Hematocrit, Ca, P, Creatinine, fluids and acid-base equilibrium). After a renal transplantation the M.C.V. presents a growing trayectory of the same mathematical pattern described before, reaching normal values about a year post-transplantion. The levels of Sodium serum follow a parallel trayectory than that one of the M.C.V. The recovery of the remainders serum parameters after renal transplantion occour during the first week, except for the hematocrit. It only remains a parallelism between the evolutive changes of M.C.V./Natremia during dialysis stage and after renal transplantion. These results seem to show a close dependence between variation of M.C.V. and Natremia. The hipoxia role over the sodium pump and the consequent variations of Natremia are discussed.

Blood Chemical Analysis↗
PubMedDate not supplied

[Left ventricular mechanics in Chagas' disease and primary dilated myocardiopathies. A hemodynamic study].

The evolution of several mechanical parameters of left ventricular function was studied in 32 control subjects, 171 chronic chagasic and 60 primary dilated cardiomyopathy patients, which were submitted to an extensive invasive and non-invasive protocol. Preload and afterload (end-diastolic and end-systolic stress), contractile status (ejection fraction), the magnitude (mass/index) and adequacy of hypertrophy (mass/volume ratio) and afterload (systolic stress/volume ratio) were derived from the invasive explorations. There was an increased afterload in 25% of chronic chagasic patients without other evidence of early myocardial damage, which was accompanied by signs of inadequate hypertrophy. Both findings increased further with the progression of the disease. Systolic performance was initially preserved, but showed a progressive depression paralleling the clinical evolution. Patients with dilated cardiomyopathy showed a mechanical profile similar to chagasic patients with advanced degree of myocardial damage. The hemodynamic determination of mass index, mass/volume ratio, end-systolic and end-diastolic stress seem to be the best parameters for detection of early abnormalities in loading conditions of the heart in chronic Chagas, disease, and for indication and evaluation of the results of vasodilator therapy in both groups of patients.

Adult↗
PubMedDate not supplied

[Contraception before pregnancy. Evolution between 1972 and 1975 in the Rhone-Alpes region (author's transl)].

The studies was made from two enquiries carried out on women who delivered in June 1972 and 1975 in the Rhone-Alpes region. Contraception therefore dealt exclusively with birth control before a pregnancy. It is clear that contraception has developed significantly: it is practised by 48% of women who were questioned in 1975 as compared with 41% in 1972. There is also a change in the last method used between the two dates: the pill featured in only 17% of all the method used in 1972 and 45% in 1975: on the other hand coitus interruptus went down from 41% to 21%. The spread of the use of the pill is a generalised phenomenon whereas there are several categories of women who do not seem to have used, coitus interruptus less frequently. As far as the social classes are concerned, it is to be pointed out that only non-skilled working-class people have not changed their habits as far as these two methods are concerned. Contraception is practised with more and more success as a method of birth control: on the one hand the number of conceptions which occurred when the women was using a birth control method has gone down from 27% in 1972 to 15% in 1975: on the other hand 51% of those who used a birth control method stopped using it in order to have a baby, whereas in 1972 only 32% did so. Parallel with this evolution, one can point out that the number of women who have 2 or more children has gone down. On the other hand the number of conceptions before marriage and the rhythm of the way the families are constituted has not changed between the two dates.

Adolescent↗