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Results for “somatic evolution”

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At least 847 records · Page 47Linked to original sources
PubMed1996

The evolution of the antiaging action of dietary restriction: a hypothesis.

Reducing the intake of dietary energy by laboratory rodents to well below that of animals allowed to eat ad libitum slows the rate of aging. This phenomenon, which is robust and reproducible, is known as the antiaging action of dietary restriction (DR). We hypothesize that this DR response arose because of its evolutionary advantage with respect to survival during periods of unpredictable, short-term food shortage. In our evolutionary scenario, food shortage led to an adaptive redirection of resources away from reproduction toward somatic maintenance via an enhanced heat shock protein response in invertebrates. In vertebrates, an additional involvement of the hypothalamic-adenohypophyseal-adrenal glucocorticoid system was necessitated to protect against excessive systemic defense responses. We suggest several general implications of our hypothesis.

Aging↗
PubMed2004

Genome diversity in microbial eukaryotes.

The genomic peculiarities among microbial eukaryotes challenge the conventional wisdom of genome evolution. Currently, many studies and textbooks explore principles of genome evolution from a limited number of eukaryotic lineages, focusing often on only a few representative species of plants, animals and fungi. Increasing emphasis on studies of genomes in microbial eukaryotes has and will continue to uncover features that are either not present in the representative species (e.g. hypervariable karyotypes or highly fragmented mitochondrial genomes) or are exaggerated in microbial groups (e.g. chromosomal processing between germline and somatic nuclei). Data for microbial eukaryotes have emerged from recent genome sequencing projects, enabling comparisons of the genomes from diverse lineages across the eukaryotic phylogenetic tree. Some of these features, including amplified rDNAs, subtelomeric rDNAs and reduced genomes, appear to have evolved multiple times within eukaryotes, whereas other features, such as absolute strand polarity, are found only within single lineages.

Journal Article↗
PubMed2003

Dmaf, a novel member of Maf transcription factor family is expressed in somatic gonadal cells during embryonic development and gametogenesis in Drosophila.

Members of the maf gene family encode basic/leucine zipper transcription factors and play important roles during cell differentiation and organogenesis in vertebrate development. In this study, we show that the maf family is evolutionarily conserved and that the Drosophila maf (Dmaf) gene is expressed in somatic gonadal cells. During embryonic development, Dmaf mRNA is detected in somatic gonadal precursor cells emerging from dorsolateral mesoderm. Relatively weak expression is also observed in subset of neuronal cells in the central nervous system. In adult flies, Dmaf is expressed in somatic gonadal cells surrounding developing oocytes and spermatocytes. These results suggest a specific function for Dmaf in gonadal development, including migration and differentiation of primordial germ cells.

Amino Acid Sequence↗
PubMed2026

Genetic control of local mutation rates.

Mutations are the source of evolutionary novelty but also the cause of genetic diseases and cancer. Mutation rates are known to be heterogeneous along the genome, however the extent to which local mutation rates vary among individuals in a population and are genetically determined is unknown. To test this, we analyzed the chromosomal distribution of somatic mutations in cell lines from 1,662 individuals, controlling for the confounding effects of DNA replication timing on local mutation rates and of trans-acting modulators on global mutation rates. We describe substantial interindividual variation in mutation rates across the human genome. By comparing mutation-rate variation to individuals' genotypes, we identified 35 instances in which polymorphic alleles in the population associate with somatic mutation rates in their vicinity. We call these mutation quantitative trait loci (mutQTLs). mutQTLs associated with somatic mutations in lymphoblastoid cell lines and in chronic lymphocytic leukemia, and with germline genetic variants. Two of the four mutQTLs inferred to be associated with germline mutation-rate variation were located within large clusters of zinc-finger genes and transposable elements, where they functioned as cis-mutators conferring an increased rate of mutation in their vicinity. mutQTLs provide a portal into the evolution of mutation rate heterogeneity across the genome and across individuals.

Humans↗
PubMed2002

What is "epi" about epigenetics?

What counts as epigenetic depends on what counts as genetic. It is argued that Weismannism, the doctrine of genetic continuity and somatic discontinuity, is the basis for an overly inclusive concept of epigenetics as every inherited resource "beyond the genes." An alternative theoretical perspective, the "reproducer" concept, is introduced to facilitate analysis of multiple inheritance systems without labeling all nongenetic inheritance "epigenetic."

Animals↗
PubMed1995

Medical histories and psychological profiles of middle-aged women with and without self-reported illness from environmental chemicals.

BACKGROUND: Cacosmia, which is a predictor of cognitive deficits in industrial samples, is a core symptom of several controversial syndromes. Previous studies of cacosmic populations have considered only psychiatric but not medical or family histories of identified patients. METHOD: This questionnaire survey study examined subjective characteristics of illness from chemical odors, sensitivity to chemicals, psychological and stress profiles, and medical, psychiatric, and family health histories of 28 middle-aged women with cacosmia in self-reported poor health attributed to chemicals (MCS), 17 controls with cacosmia in good health, and 20 normal controls without cacosmia in good health. RESULTS: Those with MCS rated themselves in significantly poorer overall health with higher Pennebaker symptom scores, a larger number of chemical triggers, and greater frequency of illness from chemicals than the other two groups, even after controlling for variables on which the groups differed (i.e., education, Symptom Checklist-90 [revised] somatization, obsessive-compulsiveness, depression, anxiety, phobic anxiety, psychoticism, Barsky Somatic Symptom Amplification, and Cheek-Buss shyness). Despite increased levels of affective distress, those with MCS reported the greatest intolerance for alcohol and the lowest alcohol consumption. CONCLUSION: The data suggest that women with MCS report increased disability, multiple medical diagnoses including inflammatory and gynecologic dysfunctions, and psychological distress. The data are consistent descriptively with the phenomenology of somatization disorder. However, the persisting significance of group health rating differences after controlling for psychological variables, the lack of differences in life stress ratings between those with MCS and healthy cacosmics, the later age at onset (60% after age 30 years), and the lack of excess family psychiatric histories in this sample of women with MCS suggest a potential role for an organic factor in the evolution of poor health in certain cacosmics.

Adult↗
PubMed1994

Clonal structural chromosome aberrations in fibrous dysplasia.

Cytogenetic analysis of short-term cultures from a case of monostotic fibrous dysplasia in a 14-year-old girl revealed multiple clonal structural rearrangements with evidence of clonal evolution. The karyotype was 46,XX,del(3)(q27),add(10)(q22),add(12)(p13)/46,idem,t(3;8)(p21;q13 ),add(10) (q26),der(15)del(15)del(15)(q15q22)ins(15;?) q15;?)/46,id em,-X,+2,t(3;8),add(10),der(15). The finding of clonal structural aberrations suggests that fibrous dysplasia is a neoplastic lesion which develops as the result of somatic mutations.

Adolescent↗
PubMed2003

Genetic structure of a population sample of apomictic dandelions.

In Northern Europe, dandelion populations consist solely of triploid or higher polyploid apomicts. Without a regular sexual cycle or lateral gene transmission, a clonal structure is expected for Taraxacum apomicts, although this was not found by compatibility analysis. In this study, we investigate whether this observation could be suported by performing independent tests based on data from hypervariable microsatellite markers as well as more conservative data based on allozymes and matrilinear cpDNA markers. In addition, population genetic methods were used to test departure from panmictic expectations, which is expected for clonal populations. Results indicated that many data sets, again, did not agree with expectations from clonal evolution because only small groups of genotypes exhibit no marker incompatibility. Population genetic analysis revealed that virtually all genotypes, but not individuals, agreed with random segregation and genotypic equilibria. Exceptions were genotypes with rare allozyme alleles or nearly identical microsatellite genotypes. Consequently, a population sample of apomictic dandelions essentially harbours genotypes that resulted from segregation and/or recombination and only a few genotypes that may have differentiated by somatic mutations.

Cluster Analysis↗
PubMedDate not supplied

Gene mapping in the spider monkey (Ateles paniscus chamek).

Sixteen isozyme markers have been assigned to the chromosome complement of the neotropical primate species Ateles paniscus chamek using three somatic cell hybrid panels. Several genetic associations were found to be common between humans and this species, despite the fact that Ateles is a karyologically rearranged taxon. Conversely, several human gene clusters were disrupted, resulting in gene associations not previously found in other primates. A comparison with other primates and mammalian orders, for which gene maps are available, was carried out for a comprehensive evaluation of genome evolution in these disparate taxa.

Animals↗
PubMed1995

Evolution of V genes: DNA sequence structure of functional germline genes and pseudogenes.

In this review we have examined the features of germline sequences of IgV genes from a number of species in an attempt to identify the "signature" of molecular mechanisms responsible for generating and maintaining diversity in the germline repertoire (after gene duplication by meiotic unequal crossover). We now summarize the relevant features point by point: 1. Codon analysis reveals a significant deficit of stop codons below the numbers that would be expected under random point mutational change. This implies that the majority of individual V genes have each been selected for the possession of open reading frames able to encode a functional Ig molecule. There is an extraordinarily high rate of apparent rescue of potential stop codons in both V genes and pseudogenes. Other (non-Ig) pseudogene sequences studied thus far do not show this high rate of rescue of stop codons. 2. The distribution of changes is concentrated in most cases in the 5' half of CDR2 (CDR2a), and coincides with the patterns of antigen-selected mutations in B lymphocytes. It does not coincide with expected non-antigen-selected (random) changes, as exemplified by hypermutated but unexpressed passenger V transgenes in B cells in Peyer's patches of unimmunized mice (Gonzalez-Fernandez and Milstein 1993). 3. In germline V genes of mice, there is no evidence of triplet codon insertion (or multiples thereof) as a mechanism generating germline diversity. This parallels a known absence of gene conversion as a mechanism generating somatic diversity in mice. In contrast, in germline chicken pseudogenes which are known to contribute to somatic generation of diversity by gene conversion, frequent examples of triplet codon insertions and deletions in CDRs are present. 4. The pattern of unique insertions and deletions in all species with sufficient sequence data available is consistent with hyper-recombination events targeting the transcription and/or coding unit. The distribution of these events does not correlate with known inducers of gene conversion, for example, inverted or direct repeats and palindromes. Furthermore, the 5' boundaries of somatic hypermutation and the 5' peak of germline nucleotide insertions and deletions coincide in IghV (Rothenfluh et al. 1993, 1994; Rogerson 1994) and in IgkV (Rogerson 1994; Rada et al. 1994, and analyses herein). It will be interesting to see how these features relate to each other in other gene sets as data become available.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2005

The etiopathogenesis of autoimmunity.

Acquisition by mammals of an adaptive immune system was an evolutionary leap, but occurred at the cost of autoimmunity. The necessity for self-recognition was appreciated in 1900, but autoimmune disease did not become a clinical reality until the 1950s-still the perimeters are indistinct. Autoimmune responses recapitulate the complex events of normal immune responses but cannot shut down. Immune tolerance is established during repertoire development centrally in thymus or bone marrow by deletion of self-reactive immunocytes, and is supplemented peripherally by regulatory T cells (Tregs). A startling discovery is the autoimmune regulator AIRE gene that enables expression of organ-specific autoantigens for intrathymic deletional tolerance of T cells. The origins, activities, and markers of Tregs are under intensive investigation. Of genes implicated in autoimmune, only few are characterized; contributions of environment are similarly uncertain. Time-latency considerations implicate stochastic factors or chance in the etiopathogenesis of autoimmunity, whether they are somatic mutations or successive random gene-environment interactions. Solutions to etiopathogenesis require novel experimental models and finely designed gene-environment studies on human populations. Perhaps immunomodulatory therapies will effect cures before causes are fully understood.

Animals↗
PubMed1999

Coelom formation: binary decision of the lateral plate mesoderm is controlled by the ectoderm.

Most triploblastic animals including vertebrates have a coelomic cavity that separates the outer and inner components of the body. The coelom is lined by two different tissue components, somatopleure and splanchnopleure, which are derived from the lateral plate region. Thus, the coelom is constructed as a result of a binary decision during early specification of the lateral plate. In this report we studied the molecular mechanisms of this binary decision. We first demonstrate that the splitting of the lateral plate into the two cell sheets progresses in an anteroposterior order and this progression is not coordinated with that of the somitic segmentation. By a series of embryological manipulations we found that young splanchnic mesoderm is still competent to be respecified as somatic mesoderm, and the ectoderm overlying the lateral plate is sufficient for this redirection. The lateral ectoderm is also required for maintenance of the somatic character of the mesoderm. Thus, the ectoderm plays at least two roles in the early subdivision of the lateral plate: specification and maintenance of the somatic mesoderm. We also show that the latter interactions are mediated by BMP molecules that are localized in the lateral ectoderm. Evolutionary aspects of the coelom formation are also considered.

Amino Acid Sequence↗
PubMed1990

Isolation of rapidly evolving genomic sequences: construction of a differential library and identification of a human DNA fragment that does not hybridize to chimpanzee DNA.

A differential library enriched in rapidly evolving human genomic sequences was obtained by phenol-enhanced hybridization of human genomic DNA with an excess of chimpanzee DNA. A DNA fragment 110 bp in length that did not hybridize to either chimpanzee or other primate DNA was identified in this library. It was shown to be a substantially diverged member of the human beta satellite family of tandem repeats. The genomic sequences homologous to the fragment were located on the short arms of human acrocentric chromosomes by in situ hybridization. The human-specific fragment failed to hybridize with RNA from different human tissues. The human-specific fragment exhibits a remarkable level of DNA polymorphism in humans and may be used in the identification of human tissue samples, in the selection of human/rodent somatic cell hybrids containing human acrocentric chromosomes, and in the mapping of these chromosomes.

Animals↗
PubMed2005

Human immunodeficiency virus type-1 episomal cDNA in semen.

BACKGROUND: Episomal 2-long terminal repeat (LTR) HIV-1 cDNA, a by-product of HIV-1 infection, is used in clinical trials as a marker for ongoing viral replication. It would be useful to employ 2-LTR cDNA to monitor cryptic HIV-1 infection in the genital tract of men on antiretroviral therapy (ART) to predict the evolution of sexually transmissible drug-resistant HIV-1, but studies thus far have failed to detect this marker in semen. The objectives of this study were: 1) to use a technique that maximizes DNA recovery from HIV-1 infected white blood cells in semen to determine if episomal 2-LTR cDNA is detectable in semen of ART-naïve men with other evidence of genital tract HIV-1 infection, and 2) to compare levels of HIV-1 2-LTR cDNA, RNA, and proviral DNA in semen from HIV-1+ men on ART. RESULTS: Using a somatic cell DNA extraction technique, 2-LTR cDNA was detected by PCR/ELISA in 4 out of 8 semen samples from ART-naïve men selected for other signs of seminal HIV-1 infection (positive controls). Southern blot and DNA sequencing confirmed that the amplified sequences were HIV-1 2-LTR cDNA; copy numbers ranged from 55 to 504 copies/sample. Two semen samples from a cohort of 22 HIV-1-infected men on dual nucleoside therapy, one with and one without detectable seminal HIV-1 RNA, were 2-LTR cDNA positive (336 and 8,560 copies/sample). Following addition of indinavir to the therapy regimen, no semen samples from 21 men with controlled peripheral and seminal viral loads were 2-LTR cDNA positive at 1 and 6 month time points, despite the persistence of HIV-1 proviral DNA+ semen cells and seminal cytomegalovirus (CMV) shedding in some cases. However, one individual who failed indinavir therapy and later developed distinct protease inhibitor (PI) drug resistance mutations in semen, maintained elevated levels of HIV-1 RNA and 2-LTR cDNA in semen. CONCLUSION: 2-LTR HIV-1 cDNA is detectable in semen of HIV-1-infected men. Two men on ART had 2-LTR HIV-1 cDNA in semen, suggesting that this marker may prove to be useful to monitor HIV-1 infection in the genital tract of men on ART to predict the evolution of drug resistance mutations in semen.

Journal Article↗
PubMed1997

Molecular cloning of a novel human gene encoding a 63-kDa protein and its sublocalization within the 11q13 locus.

A human cDNA previously isolated by virtue of its ability to complement partially the ultraviolet sensitivity of a xeroderma pigmentosum cell line was further characterized. The transcription unit is expressed as a single 4.0-kb mRNA that encodes a novel 63-kDa cytoplasmic protein, possibly initiating from an internal AUG codon. The gene encoding this protein, named UVRAG, has been extremely well conserved during evolution, implying an important role for this gene product in cell metabolism. The transcribed mRNA is constitutively expressed in a wide variety of human tissues. The protein encoded by this gene is predicted to contain a coiled-coil structure and is likely to be metabolically unstable based on the occurrence of a strong PEST domain. UVRAG was assigned to human chromosome 11 by Southern hybridization to a somatic cell hybrid panel. Fluorescence in situ hybridization coupled with PCR analysis of human/rodent somatic cell hybrids containing segments of human chromosome 11 has localized this gene to a subregion of 11q13 in between the D11S916 and the D11S906 loci. Importantly, this region has been shown to be amplified in a variety of human malignancies, including breast cancer.

Amino Acid Sequence↗
PubMed2005

Translocation t(1;6)(p35.3;p25.2): a new recurrent aberration in "unmutated" B-CLL.

Although reciprocal chromosomal translocations are not typical for B-cell chronic lymphocytic leukemia (B-CLL), we identified the novel t(1;6)(p35.3;p25.2) in eight patients with this disorder. Interestingly, all cases showed lack of somatically mutated IgV(H). Clinical, morphological, immunologic, and genetic features of these patients are described. Briefly, the age ranged from 33 to 81 years (median: 62.5 years) and the sex ratio was 6M:2F. Most of the patients (6/8) presented with advanced clinical stage. Therapy was required in seven cases. After a median follow-up of 28 months, five patients are alive and three died from disease evolution. Three cases developed transformation into diffuse large B-cell lymphoma. Translocation t(1;6) was found as the primary karyotypic abnormality in three patients. Additional chromosomal aberrations included changes frequently found in unmutated B-CLL, that is, del(11)(q), trisomy 12 and 17p aberrations. Fluorescence in situ hybridization analysis performed in seven cases allowed us to map the t(1;6) breakpoints to the 1p35.3 and 6p25.2 chromosomal bands, respectively. The latter breakpoint was located in the genomic region coding for MUM1/IRF4, one of the key regulators of lymphocyte development and proliferation, suggesting involvement of this gene in the t(1;6). Molecular characterization of the t(1;6)(p35.3;p25.2), exclusively found in unmutated subtype of B-CLL, is in progress.

Chromosomes, Human, Pair 1↗
PubMed2000

Neoteny and progenesis as two heterochronic processes involved in paedomorphosis in Triturus alpestris (Amphibia: Caudata).

Current theories on the evolution of paedomorphosis suppose that several ontogenetic pathways have appeared according to different selective pressures. The aim of this study was to find out whether two distinct processes can lead to paedomorphosis in the Alpine newt, Triturus alpestris. In this respect, we compared age structures of paedomorphic and metamorphic individuals in two newt populations where the two forms lived syntopically. Whereas paedomorphosis resulted in a slower rate of somatic development in one population, it resulted in an acceleration of sexual maturation in the other population. These processes correspond to neoteny and progenesis, respectively. These results suggest that phenotypic plasticity can result from contrasted ontogenetic pathways between two populations of the same species. They give support to models that consider gonadic development as the target of selection under different environmental pressures.

Animals↗
PubMedDate not supplied

Genetic instability and the evolution of angiogenic tumor cell lines (review).

Advanced tumor growth requires the formation of new blood vessels (angiogenesis). Whether new blood vessels are formed or not depends on a balance between angiogenesis inhibitors and promoters. Host tissue, as well as tumor cells, express inhibitory factors preventing angiogenesis. During cancer progression, tumor cell lines evolve which produce factors promoting the angiogenic switch. We use mathematical models in order to examine the conditions required for angiogenic cell lines to emerge and hence for the disease to progress. We find that genetic instability, defined as a much elevated mutation rate of somatic cells, is required for the emergence of angiogenic tumor cells. This is because a high mutation rate ensures that within a short period of time, a sufficiently high number of angiogenic cells are generated. This founder population of mutant cells is large enough to overcome the inhibitory factors produced by the tissue thereby inducing the angiogenic switch through the production of promoters. In the absence of genetic instability, angiogenic cells cannot fix, even if the relevant mutations are generated at low levels in the tumor cell population. This is because angiogenic promoters will not be sufficiently abundant to counter the influence of inhibitory factors. In this context, the inhibition of angiogenesis can be viewed as a host defense ensuring that the tumor need be genetically unstable if it is to grow and progress beyond a certain size limit. We observe that genetic instability is of value early in tumorigenesis but becomes a liability later. This is because instability decreases the fitness of the angiogenic tumor once it has become established.

Animals↗