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 1,009 records · Page 56Linked to original sources
PubMed2004

The LTR enhancer of ERV-9 human endogenous retrovirus is active in oocytes and progenitor cells in transgenic zebrafish and humans.

The solitary LTRs of ERV-9 human endogenous retrovirus are middle repetitive DNAs associated with 3,000-4,000 human gene loci including the beta-globin gene locus where the ERV-9 LTR is juxtaposed to the locus control region (beta-LCR) far upstream of the globin genes. The ERV-9 LTRs are conserved during primate evolution, but their function in the primate genomes is unknown. Here, we show that in transgenic zebrafish harboring the beta-globin ERV-9 LTR coupled to the GFP gene, the LTR enhancer was active and initiated synthesis of GFP mRNA in oocytes but not in spermatozoa, and GFP expression in the embryos was maternally inherited. The LTR enhancer was active also in stem/progenitor cell regions of adult tissues of transgenic zebrafish. In human tissues, ERV-9 LTR enhancer was active also in oocytes and stem/progenitor cells but not in spermatozoa and a number of differentiated, adult somatic cells. Transcriptional analyses of the human beta-globin gene locus showed that the beta-globin ERV-9 LTR enhancer initiated RNA synthesis from the LTR in the direction of the downstream beta locus control region and globin genes in ovary and erythroid progenitor cells. The findings suggest that, during oogenesis, ERV-9 LTR enhancers in the human genome could activate the cis-linked gene loci to synthesize maternal mRNAs required for early embryogenesis. Alternatively, the ERV-9 LTR enhancers, in initiating RNA syntheses into the downstream genomic DNAs, could transcriptionally potentiate and preset chromatin structure of the cis-linked gene loci in oocytes and adult stem/progenitor cells.

Animals↗
PubMed1979

Suicide and attempted suicide in Greenland. A controlled study in Nuuk (Godthaab).

Suicidal behaviour in Eskimo populations has changed in pattern and quantity over the last decades. Rates have more than quadrupled and performers now are mainly young persons with obscure motivation. In a study from Greenland's major township all cases of attempted or completed suicide among Greenlanders are analysed for social, emotional, somatic, and environmental predisposing factors in comparison with a non-psychiatric, never-suicidal, matching group. Almost two per thousand of the adult population committed suicide yearly while attempts at suicide were five times as frequent. A quarrelsome, drinking, childhood home background was often found, at least as regards the attempters, who themselves frequently suffered from emotional conflicts with close contacts, alcohol affliction, criminality, and instability at work. Neither bereavement, cross-cultural exposure, broken homes, nor meteorological factors seemed to exert a significant influence. The results are discussed in relation to the social and cultural evolution of the Greenlandic society.

Adult↗
PubMed1991

The X chromosome of marsupials shares a highly conserved region with eutherians.

Ten genes, located on the long arm of the human X chromosome, were mapped in several marsupial species by somatic cell analysis and in situ hybridization. All were located on the X chromosome in each species. We conclude that the long arm of the human X chromosome represents a highly conserved region that formed part of the X chromosome in a therian ancestor 120-150 million years ago, before the mammalian infraclasses diverged.

Animals↗
PubMed2001

Improvement in affinity and HIV-1 neutralization by somatic mutation in the heavy chain first complementarity-determining region of antibodies triggered by HIV-1 infection.

We assessed the impact of somatic hypermutation in the framework region 1 (FR1) and complementarity-determining region 1 (CDR1) of three clonally-related heavy chains from the human monovalent antigen-binding fragments Fab S19, S8 and S20 on gp120 binding and HIV-1 neutralization capacity. Nucleotide changes were introduced in the heavy chains to revert single and multiple amino acid residues, and two Fab libraries were constructed with the same light chain to express equivalent amounts of parental and reverted phage Fab. We studied the contribution of each amino acid replacement to antigen binding by calculating the frequency of phage Fab retrieval after competitive library selection on gp120. Whereas mutations in FR1 had no effect on antigen binding, somatic replacements in the CDR1 of the heavy chain (HCDR1) appeared to produce significant changes. In S19 HCDR1, somatic mutation of residue 32 reduced gp120 binding. In Fab S20, the Arg(30) and Asp(31) somatically replaced residues in HCDR1 improved antigen binding. Both of these residues are necessary to increase Fab binding to gp120; reversion of either residue alone results in a decrease in binding. The impact of these two replacements was confirmed by the greater neutralization capacity of S20 compared to the other Fab. Molecular modeling of S20 HCDR1 suggests that Arg(30) and Asp(31) are the main interaction sites for gp120, increasing antibody affinity and promoting the enhanced neutralization ability of S20. These findings are consistent with a gp120-driven process, supporting a role for affinity maturation and intraclonal evolution of HIV-1 neutralizing antibodies.

Amino Acid Sequence↗
PubMed2002

A new member of the NY-ESO-1 gene family is ubiquitously expressed in somatic tissues and evolutionarily conserved.

The NY-ESO-1 gene, located on chromosome Xq28, encodes a cancer/testis antigen in human. Normally expressed only in germ cells, NY-ESO-1 is activated in a wide range of human tumors, eliciting both antibody and cell-mediated immune responses in cancer patients. Clinical immunotherapeutic trials NY-ESO-1 gene products are now ongoing. A closely related gene, LAGE-1, was subsequently identified and shares similar biological features. By database search, we have identified a third member of the human NY-ESO-1 gene family. This gene, designated ESO3, is also located on the X chromosome, clustered with two exact copies of ESO1(NY-ESO-1) and one copy of ESO2(LAGE-1), within a approximately 400 kb segment. The exon-intron structures are conserved among ESO1-3. While ESO1 and ESO2(LAGE-1) share >80% protein sequence identity, homology between ESO3 and the other two members is lower (<50%). ESO3 is also distinctive in that, unlike ESO1 and 2 that are normally expressed only in testis, ESO3 messenger RNA (mRNA) is ubiquitously expressed in somatic tissues. In addition to ESO3, an intronless pseudogene highly homologous to ESO3 was found on chromosome 9, designated psiESO3.A search of the rodent databases identified mouse and rat counterparts of ESO3, named mESO3 and rESO3. mESO3 is similarly located on mouse X chromosome, with conserved exon-intron junctions. Protein sequence of mESO3 is 54% identical to ESO3 (70% identical at the conserved carboxyl end), and 32% to ESO1. mESO3 mRNA is also ubiquitously expressed in somatic tissues, as is rESO3. In addition, an intronless and presumably non-coding, copy of the mESO3, psimESO3, was identified on mouse chromosome 15. No counterpart of the ESO1 or 2 genes was found in rodents.

Alternative Splicing↗
PubMed2002

Inherited variants of MYH associated with somatic G:C-->T:A mutations in colorectal tumors.

Inherited defects of base excision repair have not been associated with any human genetic disorder, although mutations of the genes mutM and mutY, which function in Escherichia coli base excision repair, lead to increased transversions of G:C to T:A. We have studied family N, which is affected with multiple colorectal adenomas and carcinoma but lacks an inherited mutation of the adenomatous polyposis coli gene (APC) that is associated with familial adenomatous polyposis. Here we show that 11 tumors from 3 affected siblings contain 18 somatic inactivating mutations of APC and that 15 of these mutations are G:C-->A transversions--a significantly greater proportion than is found in sporadic tumors or in tumors associated with familial adenomatous polyposis. Analysis of the human homolog of mutY, MYH, showed that the siblings were compound heterozygotes for the nonconservative missense variants Tyr165Cys and Gly382Asp. These mutations affect residues that are conserved in mutY of E. coli (Tyr82 and Gly253). Tyrosine 82 is located in the pseudo-helix-hairpin-helix (HhH) motif and is predicted to function in mismatch specificity. Assays of adenine glycosylase activity of the Tyr82Cys and Gly253Asp mutant proteins with 8-oxoG:A and G:A substrates show that their activity is reduced significantly. Our findings link the inherited variants in MYH to the pattern of somatic APC mutation in family N and implicate defective base excision repair in predisposition to tumors in humans.

Amino Acid Sequence↗
PubMed1974

The organization and diversity of immunoglobulin genes.

We have used purified mouse immunoglobulin light chain mRNA and synthetic DNA which is complementary to it to assess the reiteration frequency of gene sequences corresponding to the kappa constant region of the mouse immunoglobulin light chain. These studies indicate that the constant region sequence is represented only two to three times per haploid mouse genome, a finding that rules out a simple stringent germ line mechanism which would require the constant region sequence to be represented hundreds if not thousands of times. Hybridization studies involving (125)I-labeled myeloma light chain mRNA yield interesting results which may eventually permit us to distinguish between the remaining somatic mutation and recombinational germ line hypotheses. These results reveal a major component of relatively unique frequency and a minor component with a reiteration frequency of approximately 30 to 50 copies per haploid genome. As discussed, these results do not permit us to distinguish unambiguously between a germ line model and a type of somatic mutation model that permits germ line genes corresponding to each kappa subgroup. The results do, however, clearly rule out the existence of thousands of variable region sequences so closely related to the MOPC-41 V-region as to permit extensive stable cross-hybridization.

Alleles↗
PubMed2026

Origin and evolution of colorectal mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN).

Colorectal neuroendocrine carcinoma (NEC) is a rare and aggressive cancer and in a subset of patients associated with an adenocarcinoma (AC) component. When both components exceed 30% of the tumour, it is classified as mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN), although there is an ongoing debate about whether any presence of two distinct components should be sufficient for a MiNEN diagnosis. This study aimed to investigate the origin and subsequent genetic changes of these two components. Ten colorectal cases suitable for sampling of an AC and a poorly differentiated NEC component were identified from the NORDIC NEC 2 study and sequenced across a 360-cancer gene panel. Mock phylogenetic trees were constructed from the molecular profiles of each sample within a patient. All ten cases revealed a common trunk of shared somatic mutations, including well-known colorectal cancer driver mutations such as BRAF, KRAS, APC, and TP53. In all cases, a single branching point separated the AC and NEC components. Private AC and NEC mutations generally had low variant allele frequencies, indicating that most AC and NEC cells were genetically similar. NEC, when compared with AC samples, demonstrated a higher frequency of private mutations (P = 0.009), indicating a higher mutation rate and greater ploidy (P = 0.012), suggesting an association between genomic duplication and AC-to-NEC transition. Shared mutations indicate a common clonal origin, underscoring the role of established colorectal driver mutations in the early development of these tumours, while the mechanisms underlying NEC differentiation remain poorly understood and may involve non-genetic factors.

Humans↗
PubMed1988

Simple GATCA repeats characterize the X chromosomal heterochromatin of Microtus agrestis, European field vole (Rodentia, Cricetidae).

The sex chromosomes of Microtus agrestis are extremely large due to the accumulation of constitutive heterochromatin. We have identified two prominent satellite bands of 2.0 and 2.8 kb in length after HaeIII and HinfI restriction enzyme digestion of genomic DNA, respectively. These satellites are located on the heterochromatic long arm of the X chromosome as shown using Microtus x mouse somatic cell hybrids. By in-gel hybridization with oligonucleotide probes, the organization of the two satellites was studied: among the many copies of the simple tandem tetranucleotide repeat GATA are interspersed rare single GACA tetramers. One of the satellites also harbours related GGAT simple tandem repeats. In situ hybridizations with plasmid-carried or oligonucleotide GATCA probes show clustered silver grains on the long and short arm of the X chromosome. Interspersion of differently organized (GATA)n elements is also demonstrable in the autosomal complement and on the Y chromosome. These results are discussed in the context of the evolution of vertebrate sex chromosomes in relation to heterochromatin and simple repetitive DNA sequences.

Animals↗
PubMed1988

Regional assignment of the gene for human liver/bone/kidney alkaline phosphatase to chromosome 1p36.1-p34.

We have used three different methods to map the human liver/bone/kidney alkaline phosphatase (ALPL) locus: (1) Southern blot analysis of DNA derived from a panel of human-rodent somatic cell hybrids; (2) in situ hybridization to human chromosomes; and (3) genetic linkage analysis. Our results indicate that the ALPL locus maps to human chromosome bands 1p36.1-p34 and is genetically linked to the Rh (maximum lod score of 15.66 at a recombination value of 0.10) and fucosidase A (maximum lod score of 8.24 at a recombination value of 0.02) loci. These results, combined with restriction fragment length polymorphisms identified by ALPL DNA probes, provide a useful marker for gene mapping studies involving the short arm of chromosome 1. In addition, our results help to elucidate further the structure and evolution of the human alkaline phosphatase multigene enzyme family.

Alkaline Phosphatase↗
PubMed1999

Genomic instability, DNA methylation, and natural selection in colorectal carcinogenesis.

Neoplastic transformation is increasingly understood in terms of evolutionary mechanisms, and it is now widely accepted that tumor progression involves natural selection of genetic variants occurring in the somatic environment. Here we give a review of data that substantiate this Darwinian view to tumorigenesis, with particular emphasis on recent advances related to colorectal cancer. We specifically focus on the controversies related to genomic instability and DNA methylation, and present a model, which interrelates these phenomena to the basic evolutionary concept of biology.

Cell Transformation, Neoplastic↗
PubMed1988

The use of correlated ultrastructural and morphogenetic characters in evolutionary taxonomy of hypotrich ciliates.

A new morphogenetic criterion, the "unit of turn-over" emerges from the dynamic analysis of hypotrich morphogenesis. The unit corresponds to the set of morphogenetically interdependent somatic structures whose turn-over is correlated to nuclear modifications. Hypotrichs are seen to conform to one of two very general modes of turn-over of their ciliary structures during a variety of morphogenetic processes, one in which all somatic cilia and their infraciliature are replaced, and the other in which only the cirral structures (not the dorsal dikinetids) undergo replacement. A strong correlation is observed between the type of turn-over occurring and ultrastructural features of the corresponding species. From an evolutionary point of view, these data lead to a new subdivision of hypotrichs, into the Euhypotrichina and the Pseudohypotrichina.

Animals↗
PubMed1989

The inheritance of acquired epigenetic variations.

There is evidence that the functional history of a gene in one generation can influence its expression in the next. In somatic cells, changes in gene activity are frequently associated with changes in the pattern of methylation of the cytosines in DNA; these methylation patterns are stably inherited. Recent work suggests that information about patterns of methylation and other epigenetic states can also be transmitted from parents to offspring. This evidence is the basis of a model for the inheritance of acquired epigenetic variations. According to the model, an environmental stimulus can induce heritable chromatin modifications which are very specific and predictable, and might result in an adaptive response to the stimulus. This type of response probably has most significance for adaptive evolution in organisms such as fungi and plants, which lack distinct segregation of the soma and germ line. However, in all organisms, the accumulation of specific and random chromatin modifications in the germ line may be important in speciation, because these modifications could lead to reproductive isolation between populations. Heritable chromatin variations may also alter the frequency and distribution of classical mutations and meiotic recombination. Therefore, inherited epigenetic changes in the structure of chromatin can influence neo-Darwinian evolution as well as cause a type of "Lamarckian" inheritance.

Base Sequence↗
PubMed2000

Developmental trade-offs and life histories: strategic allocation of resources in caddis flies.

Resource allocation trade-offs during development are potentially very important in the evolution of organism morphology and life-history strategy However, they have rarely been demonstrated empirically. To what extent the division of limited resources between growing organs is a consequence of particular developmental pathways or varies strategically in line with life-history predictions is unknown. It has been demonstrated in a number of holometabolous insects that altering the resources available at pupation changes the pattern of allocation to adult tissues, but this has not been examined in a life-history context. Using caddis flies (Trichoptera), we show here that the effect of depleted larval resources on the pattern of somatic and reproductive investment is not fixed but varies between species with different life-history patterns. In particular, we demonstrate that, in a long-lived species, thorax size is preserved, which contrasts with the pattern previously observed in a short-lived species. That the adult body can be differentially altered by the same resource depletion in the larvae demonstrates that the allocation of resources amongst body parts is not a consequence of fixed pathways during development. Rather, the allocation of resources during development can occur in a manner consistent with the minimization of the effects on adult fitness.

Animals↗
PubMed1994

Regional assignment of the human immunoglobulin processed pseudogene C epsilon 3 (IGHEP2) to 9p24.2-->p24.1 by fluorescence in situ hybridization.

The human immunoglobulin processed pseudogene C epsilon 3 (IGHEP2), which was assigned to chromosome 9 by somatic cell hybrid analysis, has not been regionally localized as yet. In this study, using fluorescence in situ hybridization (FISH) combined with conventional QFQ-, RBG- or GTG-banding, IGHEP2 was assigned to the p terminus region of chromosome 9, at band 9p24.2-->p24.1. This result suggests that the C epsilon 3 gene is a novel telomeric DNA marker useful not only for constructing the physical map of human chromosome 9 but also for cytogenetic analyses such as cryptic translocations. In addition, comparative mapping of this gene in other catarrhine primates would contribute to investigations of human and other primate karyotype evolution.

Cells, Cultured↗
PubMed1996

Intestinal dissemination of gastric mucosa-associated lymphoid tissue lymphoma.

Despite increasing identification of concurrent gastric and intestinal lymphomas of mucosa-associated lymphoid tissue (MALT), the clonal relationship between the two tumors and their sequential development are poorly understood. It is also unknown whether the development of these concurrent tumors is closely associated with direct antigen stimulation, which is thought to play an important role in the clonal expansion of low-grade MALT lymphomas. To investigate these, we have studied six cases of concurrent gastric and intestinal MALT lymphomas by polymerase chain reaction (PCR) amplification, cloning, and sequencing of the rearranged Ig gene, a strategy that has been widely used for analysis of clonality and antigen-driven properties of B-cell malignancies. In each case, an identical or nearly identical complementarity determining region (CDR) 3 sequence was observed between the dominant clones of concurrent gastric and intestinal MALT lymphomas. In four of six cases examined, sufficient Ig variable region sequence information was obtained to permit analysis of somatic mutations. The mutation patterns in one case suggest that the intestinal lesion is secondary to the gastric tumor, and the mutation patterns in two cases indicate that the gastric and intestinal lesions are derived from different tumour subclones, which emerge after expansion of a common early tumor clone. Furthermore, three of four cases showed ongoing Ig mutations among different PCR clones at each site. These results show that concurrent gastric and intestinal MALT lymphomas are derived from the same clone and suggest that the intestinal lesions result from dissemination of gastric tumours. Antigen stimulation may play a role in tumor evolution, particularly at an early stage.

Amino Acid Sequence↗
PubMed2006

Immunoglobulin VH somatic hypermutation in mantle cell lymphoma: mutated genotype correlates with better clinical outcome.

Mantle cell lymphoma is an aggressive B-cell lymphoma for which the biology is incompletely understood. Previous studies have reported that somatic hypermutation of the variable region of the immunoglobulin heavy chain gene (V(H)), as commonly defined as <98% homology, can be detected in approximately one-third of mantle cell lymphoma, although the V(H) mutation status has not been found to significantly correlate with patient survival. In this study, we assessed V(H) mutation in 55 mantle cell lymphomas using a method slightly different from those used in the previous studies, and we came to different conclusions. Using DNA extracted from formalin-fixed/paraffin-embedded tumors in all cases, we identified monoclonal IGH bands in 54 of 55 cases with the FR1c/J(H) primer; a monoclonal IGH band was amplified using another IGH primer set, FR256/J(H), in the remaining case. Cloning was performed in all cases, and an average of six clones were sequenced and analyzed for each case. Intraclonal heterogeneity was detected in 45 (82%) cases. Further analysis was performed in 53 cases, in which a predominant IGH species was identified. Most (32 of 53 cases, 60%) cases were 'mutated', with <98% homology. V(H)1-69, V(H)4-59 and V(H)3-74 were utilized in 29 (55%) cases. Intraclonal evolution and non-productive V(H) rearrangements were more frequent in the mutated group. Patients with the 'mutated' genotype had longer overall survival (P=0.017, Log rank) that is independent of the international prognostic index. To conclude, our data suggest that the V(H) mutation frequency in mantle cell lymphoma may be higher than previously believed. Importantly, using our methodology, we found that the V(H) mutation status may be a useful prognostic marker for these patients.

Adult↗
PubMed2006

HIV-1 Vif protein blocks the cytidine deaminase activity of B-cell specific AID in E. coli by a similar mechanism of action.

HIV-1 Vif protein protects viral replication in non-permissive cells by inducing degradation of APOBEC3G via ubiquitination and proteasomal pathway, although new studies indicate a putative role in Vif's direct inhibition of APOBEC3G. APOBEC3G is member of a homologous family of proteins with cytidine deaminase activity expressed with characteristic tissue specificity, that in humans consist of APOBEC1, APOBEC2, APOBEC3A-H, APOBEC4 and the activation-induced deaminase (AID), a B lymphoid protein necessary for somatic hypermutation, gene conversion and class switch recombination. In this work we show that Vif can counteract AID's activity in E. coli in absence of specific eukaryotic co-factors necessary for AID induced somatic hypermutation, gene conversion and to stimulate class switch recombination in B-cells. We show that AID inhibition is mediated by a direct protein-protein interaction via unique amino acid D118 an homologous mutant responsible for the species-specific restriction of HIV-1 Vif protein existent for APOBEC3G. These results raise the hypothesis that Vif related proteins can act as a broad inhibitor of deaminase activity. Moreover as AID and Vif evolved in different cellular environments, these results may indicate that Vif related proteins might mimic cellular factors that interact with a structural conserved domain of cytidine deaminases during evolution.

APOBEC-3G Deaminase↗