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 865 records · Page 48Linked to original sources
PubMed1999

Mutational analysis of the affinity maturation of antibody 48G7.

The affinity maturation of antibody 48G7 from its germline predecessor 48G7g has been studied at a molecular level through a combination of structural and biochemical means. Each of the nine somatic mutations accumulated during affinity maturation has been assessed for gain or loss of function in both the germline and affinity-matured antibodies. Individual somatic mutations were found to be either positive or neutral in their effects on affinity for hapten JWJ1, with a marked context-dependence for some sites of mutation. In a number of cases significant cooperativity was found between pairs of somatically mutated residues. Interpretation of the structural changes introduced by many of the point mutations has been possible due to the availability of high-resolution crystal structures of 48G7g and 48G7, and mechanisms by which these structural changes may result in enhanced affinity for hapten have been identified. Precise dissection of structure-function relationships in this system provides additional insights into the role of cooperativity in the evolution of antibody affinity. Comparison of 48G7 with previously characterized systems provides a varied view of the structure-function mechanisms by which the humoral immune system produces large increases in affinity.

Animals↗
PubMed2000

Immune-type diversity in the absence of somatic rearrangement.

Immunoglobulin gene diversity has been characterized to varying degrees in modern representatives of all of the major radiations of cartilaginous fish. A pattern of overall chromosomal relationships of the various types of joined and unjoined Ig gene clusters is suggested in which the essential features are: (a) both Ig heavy and light-chain gene clusters occur on multiple chromosomes, (b) various classes of Ig are interspersed, (c) not all individual gene loci appear to be closely linked (Fig. 2). The cluster-type Ig gene system appears to be a series of (potentially) individually regulated loci analogous in part to the olfactory receptor gene system (BUCK and AXEL 1991) and markedly distinct from Ig loci in other vertebrate groups and TCR genes. Such a system would be ideal for the creation of variation in both form and function in a large number of clusters while preserving or partially preserving specificity in a number of other gene clusters. The full range of joined genes and the relative number of joined genes (as relates to unjoined genes), have yet to be determined. Nevertheless, a number of conclusions can be drawn: (a) four distinct forms of heavy-chain joining have been identified (VDD-J, VD-DJ, V-D-DJ, and VDJ; Fig. 1); (b) light-chain genes, which possess only two recombining elements, can be found in either unjoined (V-J) or joined (VJ) forms (Fig. 1); (c) physical linkage between individual joined and unjoined genes has not been established, although such investigations have not been pursued in a significantly rigorous manner as to rule out this possibility; (d) joined light-chain genes are expressed and can be somatically mutated. Can germline joining be viewed as an ancestral character? The answer to this needs to be considered in the context of an overall system in which the level of structural and functional redundancy is extremely high. Joining is an adaptation that is unique to multicluster gene families. The phenomenon overcomes the possibility of not generating a specific form of a receptor, a major shortcoming of conventional rearranging Ig and TCR gene systems. The limitation of encoding specific receptors is compensated through large numbers of additional gene clusters that retain the capacity to rearrange and generate new specificities. Commitment of a V region to diverse, fixed specificity also is a property of the NITR genes, which although not related closely to Ig in a structural sense, may reflect an analogous phenomena. The possibility that immune-type diversity is achieved in the absence of somatic rearrangement and that remnants of such systems could be operative in immune recognition in contemporary vertebrates is of extraordinary significance in terms of our overall understanding of the relationships between adaptive and innate immune recognition.

Animals↗
PubMed1989

Evolutionary comparison of the avian IgL locus: combinatorial diversity plays a role in the generation of the antibody repertoire in some avian species.

Immunoglobulin light chain (IgL) diversity is generated in the chicken by recombination between the single functional variable (VL) and joining (JL) gene segments and subsequent somatic diversification of the rearranged VL region. In order to determine whether these events are a general feature of avian IgL genes, we analyzed the organization and recombinatorial characteristics of the IgL loci of several other avian species. Southern blot analysis of bursal and germline DNA using chicken VL and constant (CL) probes revealed that the IgL loci of quail, mallard duck, pigeon, turkey, cormorant, and hawk consist of a family of VL elements, but undergo a single major rearrangement event similar to that observed in chickens. In contrast, several rearrangements were observed in the Muscovy duck locus. A phage clone containing a 26 kb insert that hybridized to VL and CL probes was isolated from a Muscovy duck erythrocyte DNA genomic library. Nucleotide sequencing revealed that the clone contained a single JL-CL region flanked on the 5' side by five VL segments. Unlike the chicken, two of the VL segments (VL1, VL5) appear to be functional. The remaining three VL segments are pseudogenes that lack promoter and leader sequences, but one of these (psi VL3) has recombination signal sequences. Overall, these data indicate that rearrangement of one VL gene segment is a general feature of the IgL locus in many avian species. In these species, the presence of a family of VL elements that do not rearrange suggests that a pseudogene pool may be available for somatic diversification by gene conversion. The organization of the Muscovy duck IgL locus suggests that additional combinatiorial diversity has evolved independently in some avian species.

Amino Acid Sequence↗
PubMed1994

Ribosomal heterogeneity from chromatin diminution in Ascaris lumbricoides.

The genome of Ascaris lumbricoides encodes both germline- and soma-specific proteins homologous to the eukaryotic small ribosomal protein (Rp) S19. The two Ascaris homologs differ by 24 amino acid substitutions and are both components of the small ribosomal subunits. In oocytes, the germline RpS19 homolog (RpS19G) predominates. During chromatin diminution, however, the gene is eliminated from all presomatic cells, and RpS19G is replaced by the product of the somatic gene (RpS19S). Chromatin diminution in A. lumbricoides causes a change in the protein composition of ribosomes during development and represents an alternative means of gene regulation.

Amino Acid Sequence↗
PubMed1975

[Etiological diagnosis of spondylitis. I. Clinical, biological and radiological aspects].

The authors compared the different elements of diagnosis contributed by the clinical examination, and by laboratory and radiological investigations in 33 cases of Pott's disease and 46 cases of non-tuberculous spondylodiscitis. They show that certain elements indicate the diagnosis of Pott's disease : associated visceral tuberculosis, and a radiogram showing in particular a centro-somatic notch, recent primary infection, absence of pain, minimum signs of medullary compression ; other elements on the other hand, indicate a diagnosis of non-tuberculous spondylodiscitis : a negative cutaneous tuberculin test, a positive haemoculture, humoral signs of melitococcosis or of typhoid fever, any indication of possible means of entry of infection in the two months before the disease, radiological signs of reconstruction in the first four months of evolution, location of the lesion in the anterior upper part of the vertebra, and to a lesser degree, the acute febrile nature of the clinical picture. The authors recall that the existence of a large abscess, of which there were no examples in the present series, is an indication in favour of tuberculosis.

Adult↗
PubMed2003

Reproductive energy investment in corals: scaling with module size.

In colonial modular organisms, differences in module size and colony growth patterns among species have the potential to impose varying constraints on reproductive investment. Here, we compare reproductive output among seven morphologically different species of spawning reef corals, and analyse the relationship between reproductive output and module (polyp) size. Reproductive output ranged between 132 and 384 J cm(-2), with lipid constituting the key indicator of energy investment. Lipid decreased by 85-100%, whereas protein and carbohydrate were relatively invariant between pre- and post-spawning tissues in all species, representing 1-15% and <1%, respectively, of the energy investment to reproductive output. The ratio of energy content in reproductive to somatic tissues (gonadosomatic index, GSI) varied among species from 0.20 (Symphyllia recta) to 1.31 (Acropora tenuis), the latter being the highest value reported for any iteroparous marine invertebrate. Surprisingly, small-polyped species (Acropora, Montipora) had 2- to 6-fold higher GSIs than large-polyped ones (Lobophyllia, Symphyllia). Energy equivalents of tissues increased with the 1.50-1.76 power of polyp diameter for somatic tissues and with the 1.42-1.80 power of polyp diameter for reproductive output. In both cases, increases in energy equivalents with polyp diameter were less than the scaling exponent of 3 predicted for an isometric relationship between tissue volume (or mass) and polyp diameter, indicating significant constraints of space, design or physiological energetics with increasing polyp size. We hypothesise that such constraints have played a key role in the evolution of modularity in cnidarians.

Adaptation, Physiological↗
PubMed1996

Mouse/human sequence divergence in a region with a paternal-specific methylation imprint at the human H19 locus.

We have identified a region with characteristics of a paternal-specific methylation imprint at the human H19 locus. This region, extending from -2.0 kb upstream to the start of transcription, is heavily methylated in sperm and on the paternal allele in somatic cells. This methylation was preserved during pre-implantation. Structural analysis revealed the presence of CpG islands and a large direct repeat with a 400 bp sequence reiterated several times, but no significant sequence homology to the corresponding region of the mouse H19 gene. These findings could suggest a role for secondary DNA structure in genomic imprinting across the species, and they also present a puzzling aspect of the evolution of the H19 regulatory region in human and mouse.

Alleles↗
PubMed2002

Efficient repair of genomic double-strand breaks by homologous recombination between directly repeated sequences in the plant genome.

Previous studies demonstrated that in somatic plant cells, homologous recombination (HR) is several orders of magnitude less efficient than nonhomologous end joining and that HR is little used for genomic double-strand break (DSB) repair. Here, we provide evidence that if genomic DSBs are induced in close proximity to homologous repeats, they can be repaired in up to one-third of cases by HR in transgenic tobacco. Our findings are relevant for the evolution of plant genomes because they indicate that sequences containing direct repeats such as retroelements might be less stable in plants that harbor active mobile elements than anticipated previously. Furthermore, our experimental setup enabled us to demonstrate that transgenic sequences flanked by sites of a rare cutting restriction enzyme can be excised efficiently from the genome of a higher eukaryote by HR as well as by nonhomologous end joining. This makes DSB-induced recombination an attractive alternative to the currently applied sequence-specific recombination systems used for genome manipulations, such as marker gene excision.

Agrobacterium tumefaciens↗
PubMed2001

Molecular evolution of catalytic antibodies in autoimmune mice.

Catalytic Abs (catAbs) preferentially evolved in autoimmune MRL/MPJ-lpr/lpr (MRL/lpr) mice upon immunization with the phosphonate transition-state analogue (TSA), but this did not happen in normal BALB/c mice. The majority of the catAbs from MRL/lpr mice were from several independent clones of the same family. Most of them had a lysine at position 95 in the heavy chain (H95), which is at the junctional region. This residue, which interacts with the phosphonate moiety of the TSA and presumably is involved in the catalytic activity, was not changed even after expansive evolution following multiple mutations. By contrast, the majority that arose from BALB/c mice were the non-catAbs, which were quite different in the sequence from the catAbs from MRL/lpr mice, but they were clonally related to one another, so most of them were originated from a single clone. In the MRL/lpr mice, the catalytic subsets that existed in the initial repertoire were effectively captured by the phosphonyl oxygens in the TSA by interacting with the lysine at H95. In the BALB/c mice, however, another noncatalytic subset with only the binding capability directed to a moiety other than the phosphonate moiety was alternatively evolved, because of the lowest abundance or elimination of the catalytic subsets.

Amino Acid Sequence↗
PubMed2000

Comparative sequence analysis of the VHL tumor suppressor gene.

Comparative genome analysis may provide novel insights into gene evolution and function. To investigate the von Hippel-Lindau (VHL) disease tumor suppressor gene, we sequenced the VHL gene in seven primate species. Comparative analysis was performed for human, primate, and rodent VHL genes and for a putative Caenorhabditis elegans VHL homologue identified by database analysis. The VHL gene has two translation initiation sites (at codons 1 and 54); however, the relative importance of the full-length translation product (pVHL30) and that translated from the second internal translation initiation site (pVHL19) is unclear. The N-terminal sequence of pVHL30 contains eight copies of a GXEEX acidic repeat motif in human and higher primates, but only three copies were present in the marmoset, and only one copy was present in rodent VHL genes. Evolutionary analysis suggested that the N-terminal repetitive sequence in pVHL30 was of less functional importance than those regions present in both pVHL30 and pVHL19. The VHL gene product is reported to form complexes with various proteins including elongin B, elongin C, VBP-1, fibronectin, Spl, CUL2, and HIF-1. Although most of the regions in pVHL that had been implicated in binding specific proteins demonstrated evolutionary conservation, the carboxy-terminal putative VBP-1 binding site was less well conserved, suggesting that VBP-1 binding may have less functional significance. Although an amino acid substitution (K171T) close to the pVHL elongin binding region was found in baboon, analysis of the structure of human pVHL suggested that this substitution would not interfere with pVHL/elongin C interaction. In general, there was a good correlation between the pVHL domains that demonstrated most evolutionary conservation and those that were most frequently mutated in tumors. Analysis of human/C. elegans conservation and human germline and somatic mutation patterns identified a highly conserved mutation cluster region between codons 74 and 90. However, this region is likely to be important for the structural integrity of pVHL rather than representing an additional protein binding domain.

Amino Acid Sequence↗
PubMed2004

Histone H1 and the origin of protamines.

We present evidence that chordate protamines have evolved from histone H1. During the final stages of spermatogenesis, the compaction of DNA in many organisms is accomplished by the replacement of histones with a class of arginine-rich proteins called protamines. In other organisms, however, condensation of sperm DNA can occur with comparable efficiency in the presence of somatic-type histones or, alternatively, an intermediate class of proteins called protamine-like proteins. The idea that the highly specialized sperm chromosomal proteins (protamines) and somatic chromosomal proteins (histones) could be related dates back almost to the discovery of these proteins. Although this notion has frequently been revisited since that time, there has been a complete lack of supporting experimental evidence. Here we show that the emergence of protamines in chordates occurred very quickly, as a result of the conversion of a lysine-rich histone H1 to an arginine-rich protamine. We have characterized the sperm nuclear basic proteins of the tunicate Styela montereyensis, which we show consists of both a protamine and a sperm-specific histone H1 with a protamine tail. Comparison of the genes encoding these proteins to that of a sister protochordate, Ciona intestinalis, has indicated this rapid and dramatic change is most likely the result of frameshift mutations in the tail of the sperm-specific histone H1. By establishing an evolutionary link between the chromatin-condensing histone H1s of somatic tissues and the chromatin-condensing proteins of the sperm, these results provide unequivocal support to the notion that vertebrate protamines evolved from histones.

Amino Acid Sequence↗
PubMed1988

Human tyrosinase gene, mapped to chromosome 11 (q14----q21), defines second region of homology with mouse chromosome 7.

The enzyme tyrosinase (monophenol,L-dopa:oxygen oxidoreductase; EC 1.14.18.1) catalyzes the first two steps in the conversion of tyrosine to melanin, the major pigment found in melanocytes. Some forms of oculocutaneous albinism, characterized by the absence of melanin in skin and eyes and by a deficiency of tyrosinase activity, may result from mutations in the tyrosinase structural gene. A recently isolated human tyrosinase cDNA was used to map the human tyrosinase locus (TYR) to chromosome 11, region q14----q21, by Southern blot analysis of somatic cell hybrid DNA and by in situ chromosomal hybridization. A second site of tyrosinase-related sequences was detected on the short arm of chromosome 11 near the centromere (p11.2----cen). Furthermore, we have confirmed the localization of the tyrosinase gene in the mouse at or near the c locus on chromosome 7. Comparison of the genetic maps of human chromosome 11 and mouse chromosome 7 leads to hypotheses regarding the evolution of human chromosome 11.

Animals↗
PubMed2005

The angiotensin-converting enzyme (ACE) gene family of Anopheles gambiae.

BACKGROUND: Members of the M2 family of peptidases, related to mammalian angiotensin converting enzyme (ACE), play important roles in regulating a number of physiological processes. As more invertebrate genomes are sequenced, there is increasing evidence of a variety of M2 peptidase genes, even within a single species. The function of these ACE-like proteins is largely unknown. Sequencing of the A. gambiae genome has revealed a number of ACE-like genes but probable errors in the Ensembl annotation have left the number of ACE-like genes, and their structure, unclear. RESULTS: TBLASTN and sequence analysis of cDNAs revealed that the A. gambiae genome contains nine genes (AnoACE genes) which code for proteins with similarity to mammalian ACE. Eight of these genes code for putative single domain enzymes similar to other insect ACEs described so far. AnoACE9, however, has several features in common with mammalian somatic ACE such as a two domain structure and a hydrophobic C terminus. Four of the AnoACE genes (2, 3, 7 and 9) were shown to be expressed at a variety of developmental stages. Expression of AnoACE3, AnoACE7 and AnoACE9 is induced by a blood meal, with AnoACE7 showing the largest (approximately 10-fold) induction. CONCLUSION: Genes coding for two-domain ACEs have arisen several times during the course of evolution suggesting a common selective advantage to having an ACE with two active-sites in tandem in a single protein. AnoACE7 belongs to a sub-group of insect ACEs which are likely to be membrane-bound and which have an unusual, conserved gene structure.

Amino Acid Sequence↗
PubMed1991

[Prolonged erythrocytic T activation, depression of blood group A and increase of fetal hemoglobin in a myelodysplastic syndrome evolving into erythroleukemia].

T cryptantigen can be exposed on the red cell membrane as a result of removal of terminal glycosides, either by bacterial enzymes or by incomplete synthesis of the cell membrane due to somatic mutation, usually caused by a neoplasm. T-activated erythrocytes have been observed in different pathologies, but they have not been seen associated with other abnormalities of red blood cell proteins described in myelodysplastic syndromes or acute leukaemias. A patient with initial diagnosis of refractory anaemia that evolved into erythroleukaemia showed prolonged T-activation, a depressed A blood-group antigen and an increase of foetal haemoglobin, simultaneously. The evolutive pattern of T-activation suggests more an abnormal erythropoiesis than an enzymatic effect and a certain relationship with the haemolytic syndrome.

ABO Blood-Group System↗
PubMed2004

In vitro antibody evolution targeting germline hot spots to increase activity of an anti-CD22 immunotoxin.

Recombinant immunotoxin BL22, containing the Fv portion of an anti-CD22 antibody, produced complete remissions in most patients with drug-resistant hairy cell leukemia but had less activity in leukemias with low CD22 expression. Complementarity-determining region (CDR) mutagenesis is used to increase antibody affinity but can be difficult to perform successfully. We previously showed that antibodies with increased affinity and immunotoxins with increased activity could be obtained by directing mutations at specific DNA residues called hot spots. Because hot spots can arise either by somatic mutation or be present in the germline, we examined which type of hot spot is preferred for increasing antibody affinity. Initially, a second generation antibody phage-display library targeting a germline hot spot (Ser(30)-Asn(31)) within CDR1 of the antibody light chain was mutated. Substitution of serine 30 or asparagine 31 with arginine produced mutant immunotoxins with an affinity (0.8 nM) increased 7-fold over BL22 (5.8 nM) and 3-fold over the first generation mutant HA22 (2.3 nM). More importantly, a 10-fold increase in activity over BL22 and a 2-3-fold increase over HA22 were observed in various B lymphoma cell lines including WSU-CLL that contains only 5500 CD22 sites per cell. For comparison, two phage-display libraries targeting non-germline hot spots in heavy chain CDR1 and CDR3 were generated but did not produce Fv with increased affinity. Our results demonstrate that germline hot spots but not non-germline hot spots are effective for in vitro antibody affinity maturation.

Amino Acid Sequence↗
PubMed2002

The colonial urochordate Botryllus schlosseri: from stem cells and natural tissue transplantation to issues in evolutionary ecology.

The urochordates, whose stem groups may have included the direct predecessors of the chordate line, serve as an excellent model group of organisms for a variety of scientific disciplines. One taxon, the botryllid ascidian, has emerged as the model system for studying allorecognition; this work has concentrated on the cosmopolitan species Botryllus schlosseri. Studies analyzing self-nonself recognition in this colonial marine organism point to three levels of allorecognition, each associated with different outcomes. The first level controls natural allogeneic rejections and fusions, in which blood-shared chimeras are formed. The second level leads to morphological resorption of partners within chimeras while the third allows the development of somatic and germ cell parasitic events. Recent studies on multi-chimeric entities formed in allogeneic fusions reveal evolutionary links between allorecognition, stem cell biology and ecology. Thus, the Botryllus system generates perspectives from different biological disciplines to yield a unique life history portrait.

Animals↗
PubMed1996

Varieties of paw and digit movement during spontaneous food handling in rats: postures, bimanual coordination, preferences, and the effect of forelimb cortex lesions.

This study describes how rats use their paws and digits when handling a wide range of foodstuffs, including food pellets, grapes, sunflower seeds, shelled and unshelled peanuts, and different sized pastas, etc. Analysis of videorecordings show that the rats display digit postures that include variations in the spacing of the digits, differences in the relative use of different digits, and interlimb differences in paw and digit posture. The rats also display limb preferences in that one paw is used in a supporting function while the other rotates, flips, or pushes the food as is required by the shape of the item. There is a significant correlation between the paw used for manipulation and food items of similar shape but no correlation between the limb used for manipulation and that used for skilled reaching. Small unilateral lesions to the forepaw area of somatic sensorimotor cortex produced impairments in use of the paw contralateral to the lesions. These results: (1) reveal a surprising complexity in the way in which rats use their paws and digits in manipulating food; (2) show that rats have limb preferences in spontaneous food handling; and (3) show that manipulatory dexterity is dependent upon the integrity of the forelimb area of motor cortex. The results are discussed in relation to the evolution of motor skill, the use of rats for investigating questions of motor system organization, neural plasticity, and recovery of function after brain damage.

Animals↗
PubMed2006

The Paton individual-based model legacy.

Ray Paton oversaw the creation of a long lineage of Individual-based Models (IbMs) and this paper discusses the five most successful. All of these concern the development of adaptation, covering both evolutionary time and organism lifetime (somatic time). Of the five models discussed here, the first is based on a plant-herbivore model, the other four are based on a substrate-bacteria model, with the option of antibiotics.

Adaptation, Physiological↗