Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “somatic evolution”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,117 records · Page 62Linked to original sources

The regulation and biological significance of genomic imprinting in mammals.

Genomic imprinting is a system of non-Mendelian inheritance that is unique to mammals. Two types of imprinted genes show parent-of-origin-specific expression patterns: the paternally expressed genes (Pegs), and the maternally expressed genes (Megs). Parental genomic imprinting memory is maintained in the somatic cell lineage and regulates the expression of Pegs and Megs, while it is erased and re-established in the germ cell lineage according to the sex of the individual. The paternal and maternal imprinting mechanisms, which regulate different sets of Pegs and Megs, are essential for establishing the parental expression profiles of imprinted genes that are observed in sperms and eggs. Based on recent evidence, we outline the relationship between parental imprinting and the expression profiles of Pegs and Megs and discuss a novel view of the regulation of genomic imprinting. We also discuss the biological significance of genomic imprinting and propose hypotheses on the essential nature of genomic imprinting and the close relationship between genomic imprinting and the acquisition of placental tissues during mammalian evolution.

Animals↗

Assignment of a Mus musculus gene for triosephosphate isomerase to chromosome 6 and for glyoxalase-I to chromosome 17 using somatic cell hybrids.

Chinese hamster X mouse hybrid cells segregating mouse chromosomes have been used to assign a gene for triosephosphate isomerase (TPI-1, EC 5.3.1.1, McKusick No. 19045) to mouse chromosome 6, and a gene for Glyoxalase-I (GLO-1, EC 4.4.1.5, McKusick No 13875) to mouse chromosome 17. The genes for TPI-1 and lactate dehydrogenase B are syntenic in man and probably so in the dog. It is therefore likely that they are syntenic also in the mouse. It is of interest then that there is a mouse gene, Ldr-1, on chromosome 6 that regulates the level of LDH B subunits in mouse erythrocytes. The locus for GLO-1 is closely linked to the major histocompatibility complex in man. Since the major histocompatibility complex in the mouse is present on chromosome 17, this locus and the Glo-1 locus are syntenic in the mouse as well. This finding adds to the number of autosomal gene pairs which are syntenic in both mouse and man and reinforces the belief that there is considerable conservation. of linkage groups during evolution.

Animals↗

Immunology and embryogenesis: the chromosomal editing hypothesis.

We have elaborated the chromosomal editing hypothesis of development. This hypothesis, based on evolutionary arguments, states that the immune system must have evolved from pre-existent cell receptor systems on other tissues. Therefore we feel that what we know about development in the immune system can serve as a provisional model for studying development in other organ systems. The model predicts that specifically programmed somatic-genetic events occur as lineages develop. These DNA cutting and splicing events, similar to those which generate antibody molecules, generate a wide diversity of specific cell receptors which allow the cell to properly orient itself in the developing organism. In addition, the chromosomal editing events occur sequentially and generate a temporal organization so that developmental events occur in an orderly fashion as lineages develop. At any point in development, epigenetic factors play a crucial role in triggering cells to undergo specific differentiative events. We believe that this hypothesis explains the apparent contradiction between rigid mosaic development and regulative development by proposing that the same general types of somatic-genetic and epigenetic events occur in both. In mosaic development, however, the organism does not have the residual and redundant stem cells which allow for the cell replacement, repair and regeneration seen in regulative development. We feel that by drawing analogies as we have from the development of the immune system one may gain insights into the genetic and epigenetic factors which govern the development of other tissues and formulate specific experiments to test the resulting hypothesis.

Biological Evolution↗

Murine alpha-fetoprotein and albumin: two evolutionarily linked proteins encoded on the same mouse chromosome.

Several lines of evidence suggest a close functional relationship and a common evolutionary origin for alpha-fetoprotein and albumin. In the mouse, breeding studies have previously allowed the assignment of the albumin gene to chromosome 5. To test the possible linkage of alpha-fetoprotein and albumin, five somatic cell hybrids containing various combinations of mouse chromosomes, together with a constant set of hamster chromosomes, were tested for the presence of both genes using DNA restriction mapping techniques. Two of the five hybrids possessed both genes, and the other three lacked both. The only mouse chromosome present in the positive lines and absent from the negative ones was number 5, allowing the assignment of both genes to this chromosome.

Animals↗

[Post-traumatic stress disorder (PTSD): the syndrome with multiple faces].

We choose to discuss from the PTSD's point of view because this diagnostic reference is commonly used. We wish outline its restrictive sight which could prevent the professional from having a diagnosis of PTSD. We don't want to say there is a PTSD everywhere but it appears to us that a traumatic reading can be a precious advantage for the clinician to establish a real therapeutic relation with some patients. Post-traumatic syndrome differs from the majority of other diagnostic categories as it includes in its criteria the presumptive cause of the trauma (criterion A). In the case that this syndrome originates in war experiences, the presumed cause presents itself as an exceptional event overcoming the individual's resources. The notion of war traumatisation has been extended to other events such as catastrophes, physical attacks, rapes, child and wife battering, and sexual abuses. But the events which cause PTSD (Post-Traumatic Stress Disorder) are significantly more numerous. It can be seen that medical events such as giving birth, miscarriage, heart attack, cancer, or hospitalisation following resuscitation may give rise to PTSD. Further, people experiencing prolonged periods of distress may equally develop a post-traumatic syndrome without any particular event having occurred to surpass their defences. It's the case of the Prolonged Duress Stress Disorder (PDSD). The series of discontinuous stress "waste" the psychic balance and may give rise, at one moment, to posttraumatic symptoms described in DSM, without any specific stressful event. The existence of criterion A is therefore not a necessary prerequisite in establishing a diagnosis of PTSD. It is, in fact, very difficult to predict which events could cause a PTSD, and this, especially, as the subjective aspects count at least as much as the objective aspects. The clinician should have to carefully explore how the patient experienced the event or, how he apprehended the event itself and it's outcome, if he wants get the traumatic range of a life event. The feeling of deep distress, the feeling of being trapped, the loss of control, the collapse of basic beliefs, the feeling that one's life is in jeopardy, that the physical integrity is (really or in one's imagination) threatened, the feeling of helplessness, are quite as much clues for a possible PTSD which hides behind others clinical manifestations either psychological or somatic. Furthermore, the "pure" form described in the DSM and grouping together three further criteria (reliving events, avoiding stimuli associated with the trauma, hyper-reactivity) is extremely rare in the chronic form. An untreated post-traumatic syndrome evolves with time and may present, initially, with very different pathological symptoms giving rise to equally varied diagnoses. Different etiopathogenic models propose to account for the PTSD 's heterogeneous appearance and instability with time. The comorbidity concept sees the PTSD as an independent entity other independent pathologies coexist with. The typologic concept suggests that the PTSD is an independent entity which shows different clinical appearances based on symptomatic descriptions. The "cascade" concept suggests to see the PTSD as an independent entity which offers, with time, different symptomatic appearances, in evolution, because of events caused by after effects, in different areas of the PTSD itself. All of these concepts outline the transnosologic appearance of the PTSD which makes it hardly recognizable. The "chronic" syndrome is rarely diagnosed forming a real challenge to prevention. In effect, the present authors insist on the crucial nature of early detection of PTSD since the greater the time elapsed the more difficult it becomes due to the evolutionary aspect of the syndrome, which initially has more readily recognizable symptoms. The consequences of an unrecognised PTSD are serious and affect both the individual and his immediate family and friends, contributing further to the aggravation of the problems. When a PTSD is diagnosed, it can allow the clinician to further a more global care which will help the patient to get a better recovery. With patients who suffered an infarct, the treatment of PTSD which prevents their recovery will help to go back to the way they lived before the event. It has been showed how important could be the PTSD detection on the severe burned people's pain control. Thus it seems to be crucial for the clinician to keep this diagnosis in mind alongside any other.

Adolescent↗

A somatic reproductive organ enhancer complex activates expression in both the developing and the mature Drosophila reproductive tract.

The Glucose dehydrogenase (Gld) gene is highly expressed in the mature Drosophila reproductive tract. Unlike several other Drosophila genes which function in reproductive physiological processes, Gld is also expressed extensively in the developing reproductive tract during metamorphosis. Proximal promoter elements drive Gld expression in a variety of tissues throughout development, but not in the reproductive tract. Herein, we have identified a somatic reproductive organ enhancer complex (SREC) containing multiple redundant enhancer modules in Gld intron I (+639 to +3906 nt). The SREC, in combination with the Gld promoter, activates beta galactosidase reporter gene expression in both the developing and the mature reproductive tract. The SREC activates a heterologous hsp70 promoter in the ejaculatory duct, but not in other reproductive tract tissues, suggesting that the SREC acts synergistically with Gld promoter proximal elements. Through deletion analysis we have delimited a 361-nt region of the SREC that is involved in ejaculatory duct/oviduct-specific expression. The ejaculatory duct/oviduct enhancer retains the ability to activate expression in both the developing and the mature reproductive tract, suggesting that the same basic enhancer elements activate Gld expression during metamorphosis and in adults. A model of the evolution of Gld expression in the ejaculatory duct and oviduct is presented.

Animals↗

Spontaneous occurrence of a Robertsonian fusion involving chromosome 19 by single whole-arm reciprocal translocation (WART) in wild-derived house mice.

Chromosomal races of the house mouse (Mus musculus domesticus) bear Robertsonian (Rb) fusions, which consist of centric translocations between two non-homologous acrocentric chromosomes. The high level of diversity of these fusions in house mice is generated by de-novo formation of Rb fusions and subsequent whole-arm reciprocal exchanges (WARTs). This paper describes the spontaneous occurrence of a new Rb fusion, Rb(4.19), in progeny of wild-derived house mice segregating for Rb(4.12). The chromosomal mutation was traced to a female which exhibited germline and somatic mosaicism indicating an early embryonic origin of the mutation. FISH analysis of centromerically-located ribosomal genes suggested that no modification was observed on chromosomes 12 and 19 prior to or following the occurrence of Rb(4.19). Distribution of telomeric sequences showed that both Rb fusions lacked telomeres in their centromeric regions. It is argued that this spontaneous mutation most likely originated by single whole-arm reciprocal translocation (WART) between Rb(4.12) and an acrocentric chromosome 19, resulting in Rb(4.19) and a neo-acrocentric chromosome 12. Sequences required for centromeric function and proximal telomeres would have been transferred to the neo-chromosome 12 from chromosome 19 during the translocation. The existence of such WARTs which generate derived acrocentric chromosomes has several implications for chromosomal evolution in house mice.

Animals↗

Ovarian ageing and the general biology of senescence.

Ovarian ageing is not only of major importance in its own right but is also of interest for its relationship with the general biology of senescence. A key feature of ageing is the distinction in higher animals between the immortality of the germ-line and the mortality of somatic cells and tissues. The ovary contains the female germ cells, and it is through these cells that the female contribution to germ-line immortality is effected. It is abundantly clear that individual oocytes can and do age and that the ageing of the ovary plays a major role in initiating or accelerating a series of other senescent changes. To understand how ovarian ageing fits within the general biology of senescence, it is necessary to explain why ageing occurs at all, to examine the likely mechanisms of general ageing, and to ask whether there is anything special about ovarian ageing and its relationship with the human menopause. Research on ovarian ageing interacts with the our emerging understanding of the general biology of senescence at many levels, ranging from the evolution of the human life history to the biochemical and cellular mechanisms of ageing and longevity.

Aging↗

An update on the role of epidermal growth factor receptor inhibitors in non-small cell lung cancer.

Within the past 2 years, epidermal growth factor receptor (EGFR) inhibitors have moved from experimental agents to approved drugs for the management of advanced non-small cell lung cancer (NSCLC). This evolution has been accompanied by dramatic improvements in the understanding of how these drugs work and the clinical populations that may benefit. The identification of mutations in the ATP-binding domain of the EGFR that predict for dramatic responses introduces the possibility of truly individualized therapy in a subset of advanced NSCLC patients. The fact that these mutations may be more prevalent in certain patient populations, including patients of Asian ethnicity, female gender, and never-smoker status, raises intriguing questions regarding the pathogenesis of lung cancer. Another emerging area in the understanding of these agents revolves around the clinical observation that acneform rash may predict for superior outcome and the question of how this rash may relate to polymorphisms in the EGFR gene. EGFR polymorphisms, both germline and somatic, may be a relevant factor in unraveling the mechanism of the benefit of erlotinib in patients who do not harbor an EGFR ATP-binding site mutation. Numerous questions have arisen regarding how to best incorporate EGFR-targeted agents into patient management, as well as the role of the clinical laboratory in these decisions and the design of future trials.

Antineoplastic Agents↗

Speculations on the origin of the vertebrate immune system.

As one studies more and more the immune systems of invertebrates their multiplicity and diversity increase. On one hand, the number of different local and systemic innate mechanisms (or cascades of mechanisms) increases with every phylum studied, on the other hand the diversity increases within each system as multiple loci and polymorphisms are discovered. Even somatic variation is not restricted to vertebrates. Yet no immune system similar to that of vertebrates characterized by the usage of RAG enzymes, has been found below jawed vertebrates. The availability of genome projects in early chordates allows understanding better the different causal lines that led to the generation of the vertebrate system with its diverse repertoire of antigen receptors generated somatically. This paper singles out a linkage group in human, gathering genes of the Ig superfamily with structural relationships to the antigen receptor JAM/CTX, nectin, or to some haematopoietic cells CD that have homologues in protochordates such as Branchiostoma and Ciona or in more primitive protostomes. The role of virus receptor for many of these clustered genes products provides perhaps one way of envisaging the recruitment of this family in the adaptive immune system from an ancient form of innate antiviral immunity.

Animals↗

Genetic mapping in mammals: chromosome map of domestic cat.

A genetic map of 31 biochemical loci located on 17 feline syntenic (linkage) groups has been derived by somatic cell genetic analysis of cat-rodent hybrids. Most of these syntenic groups have been assigned to one of the 19 feline chromosomes. Comparative linkage analysis of the feline biochemical loci and homologous human loci revealed considerable conservation of linkage associations between the primates and the Felidae (order Carnivora). Many of these same linkage groups have not been conserved in the murine genome. The genetic and evolutionary implications of comparative mapping analysis among mammalian species are discussed.

Animals↗

A possible basis for major histocompatibility complex-restricted T-cell recognition.

Four distinct T-cell antigen-receptor gene loci have now been identified and partly characterized: alpha, beta, gamma and delta. All of these loci can rearrange in an immunoglobulin-like fashion and express polypeptides that contribute to either alpha:beta or gamma:delta T-cell receptor-CD3 complexes. Surprisingly, the T-cell receptor (TCR) delta coding regions are located entirely, or almost entirely, within the TCR alpha locus and share at least some of the V region gene segments, thus at least partly linking the two different types of receptor heterodimers. Analysis of potential T-cell receptor diversity, particularly that of the delta chain, indicates a striking concentration of somatic polymorphism in the V-J junctional region of the two heterodimers, four to six orders of magnitude higher than similar calculations for immunoglobulin light- and heavy-chain combinations. In contrast, the number of possible V region combinations in T-cell receptors is one hundredth to one thousandth that of immunoglobulins. TCR alpha: beta heterodimers are known to recognize many possible fragments of antigens embedded in the peptide-binding clefts of a relatively small number of major histocompatibility complex (MHC) molecules. Thus it is attractive to speculate that the V-J junctional portions of both types of T-cell receptor contact peptide antigens, whereas the remaining diversity regions contact the MHC. This contention is supported by molecular modelling studies and has interesting implications for the evolution of antigen-receptor genes.

Antibody Diversity↗

Brachypodium distachyon. A new model system for functional genomics in grasses.

A new model for grass functional genomics is described based on Brachypodium distachyon, which in the evolution of the Pooideae diverged just prior to the clade of "core pooid" genera that contain the majority of important temperate cereals and forage grasses. Diploid ecotypes of B. distachyon (2n = 10) have five easily distinguishable chromosomes that display high levels of chiasma formation at meiosis. The B. distachyon nuclear genome was indistinguishable in size from that of Arabidopsis, making it the simplest genome described in grasses to date. B. distachyon is a self-fertile, inbreeding annual with a life cycle of less than 4 months. These features, coupled with its small size (approximately 20 cm at maturity), lack of seed-head shatter, and undemanding growth requirements should make it amenable to high-throughput genetics and mutant screens. Immature embryos exhibited a high capacity for plant regeneration via somatic embryogenesis. Regenerated plants display very low levels of albinism and have normal fertility. A simple transformation system has been developed based on microprojectile bombardment of embryogenic callus and hygromycin selection. Selected B. distachyon ecotypes were resistant to all tested cereal-adapted Blumeria graminis species and cereal brown rusts (Puccinia reconditia). In contrast, different ecotypes displayed resistance or disease symptoms following challenge with the rice blast pathogen (Magnaporthe grisea) and wheat/barley yellow stripe rusts (Puccinia striformis). Despite its small stature, B. distachyon has large seeds that should prove useful for studies on grain filling. Such biological characteristics represent important traits for study in temperate cereals.

Anti-Bacterial Agents↗

The interleukin-6 gene locus seems to be a preferred target site for retrotransposon integration.

Recently, we have observed the insertion of a retrotransposon into the interleukin-6 (Il-6) locus of a mouse somatic cell line. Here we report the characterization of Il-6 genomic regions from both mouse and rat. Restriction site analysis, DNA sequence analysis, and computer-assisted search revealed eight retrotransposon-like elements distributed over a 25 kilobase (kb) mouse Il-6 region. In the rat, five different retrotransposons have been identified within a 17 kb Il-6 region. The retrotransposons belong to the LINE-, Alu I or Alu II families, or to a rat specific class of retrotransposons. Some of the retrotransposons exhibit characteristic features such as target site duplication and a poly A-tract. Remarkably, several retrotransposons map to different chromosomal locations in the mouse and rat. A genealogical tree of mouse, rat, and human Il-6 loci demonstrates a series of retrotranspositions that recently occurred in evolution. These results suggest that the Il-6 locus serves as a preferred target site for retrotransposon integration during evolution.

Animals↗

[The risk of congenital malformations and genomic imprinting defects in assisted reproductive technologies and nuclear transfer cloning].

Recent studies show that assisted reproductive technologies (ART), whether in vitro fertilization (IVF) or intra-cytoplasmatic sperm injection (ICSI) or applied to cloning by somatic cell nuclear transfer (SCNT) are associated to a higher risk of congenital malformations and errors in deprogramming, maintenance or reprogramming genomic imprinting in humans and animals. IVF and ICSI are also associated to an increased admission to neonatal intensive care units and more need for health care resources in infancy. A mutagenic effect of a chemical used in SCNT has been reported and gene depression was found in bovine embryos obtained by IVF or SCNT. The causes of these anomalies could be pathological conditions for which ART is applied, a direct effect of technologies on the zygotes or embryos, avoidance for zygotes or embryos of the oviduct path that is needed to elicit necessary immunity or genomic programming processes, or adaptive selective steps acquired during thousands of millions of generations in evolution. The knowledge of evolution is emphasized as essential in the scientific ethical analysis.

Animals↗

Identification of two distinct subfamilies of alpha satellite DNA that are highly specific for human chromosome 15.

We report the isolation of two distinct subfamilies of alpha satellite DNA (pTRA-20 and -25) from human chromosome 15. In situ hybridization experiments indicated that both subfamilies are highly specific for this chromosome. Southern analysis of a somatic hybrid cell line carrying human chromosome 15 revealed a likely higher-order genomic band of 2.5 kb for pTRA-20. Similar analysis for pTRA-25 showed multiple higher-order bands of 3.5, 4.5, and 5 kb at moderately high hybridization stringency, but a predominance of the 4.5-kb species at very high stringency. Direct comparison with human genomic DNA confirmed the authenticity of these higher-order structures and demonstrated polymorphic variations using both probes. The origin of the different alphoid subfamilies on chromosome 15 is discussed. These sequences should be useful for the construction of centromere-based genetic linkage maps for human chromosome 15 and, in conjunction with the other alphoid sequences already reported for chromosomes 13, 14, 21, and 22, should allow a concerted analysis of the evolution and the possible etiological role of these DNAs in aberrations commonly seen in these chromosomes.

Blotting, Southern↗

Antigen selection in the IgE response of allergic and nonallergic individuals.

BACKGROUND: Affinity maturation within germinal centers should usually lead to an accumulation of replacement mutations in complementarity-determining regions (CDRs) of Ig genes as a result of antigen selection. A number of studies have suggested, but not statistically demonstrated, that antigen selection might not guide such an accumulation of replacement mutations in allergic IgE sequences. This has been suggested to reflect the nature of allergens themselves or of the allergic response. OBJECTIVE: We sought to investigate the role of antigen selection in the evolution of the IgE response by mean of analysis of Ig sequences derived from both allergic and nonallergic individuals. METHODS: IgE sequences were amplified from peripheral blood of allergic and nonallergic individuals by using seminested RT-PCR. Additional IgE and IgG sequences were obtained from public databases. Analysis considered replacement mutations in the CDRs as a proportion of total mutations and compared IgE sequences with IgG sequences. RESULTS: The nonallergic IgE sequences were significantly less mutated than both the allergic IgE (P < .001) and IgG (P < .01) sequences. There was a low proportion of replacement mutations in the CDRs of both nonallergic and allergic IgE sequences and a significantly increased proportion of such mutations in IgG sequences (P < .001). CONCLUSIONS: IgE antibodies in both nonallergic and allergic individuals appear to accumulate few somatic point mutations as a consequence of antigen selection. CLINICAL IMPLICATIONS: Allergic and nonallergic IgE responses might often develop along a common pathway that is distinct from the conventional germinal center reaction through which the IgG response develops.

Allergens↗

Analysis of the kappa light chain variable region in multiple myeloma.

The study of immunoglobulin heavy chain gene rearrangements in multiple myeloma has revealed extensive divergence from the germline sequences, but no intraclonal diversity with disease evolution. Our study investigated the state of the rearranged kappa light chain variable region (V kappa) gene segments as well as abortive V kappa family gene usage in cases of multiple myeloma expressing lambda light chain. We studied 11 cases of kappa and five cases of lambda light chain-expressing multiple myeloma. Total cellular RNA was extracted from the bone marrow of patients with overt disease and subjected to reverse transcription-polymerase chain reaction (RT-PCR) analysis to amplify clonally rearranged variable region sequences. Direct nucleotide sequencing by the dideoxy-chain termination method was performed on the RT-PCR products. We did not observe preferential usage of certain V kappa gene families. Mutation frequencies of the V kappa segments varied in number. In the majority of cases, extensive somatic mutations occurred within the complementarity determining regions (CDRs) of V kappa, whereas only a limited degree of divergence from the germline was observed in others. In all cases studied. replacement mutations tended to cluster in the CDRs, a finding compatible with an antigen-driven somatic hypermutation process. In 3/5 cases of lambda light-chain expressing multiple myeloma, abortively rearranged V kappa gene segments were amplified from genomic DNA; in two cases a non-templated nucleotide insertion rendering the V kappa sequences out-of-frame was observed, and in the third a stop codon was identified in the open reading frame of the V kappa sequence. Somatic mutations were observed in all cases of abortive V kappa genes studied; however, their distribution does not suggest selection by antigen. We conclude that somatic mutations observed in the V kappa regions of myeloma cells are of variable extent and suggest operation of the antigen selection process. Lack of or minimal somatic hypermutation in a few cases may be in some way implicated in the biological heterogeneity of the disease.

Amino Acid Sequence↗