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PubMed1998

Evolution of oogenesis: the receptor for vitellogenin from the rainbow trout.

Receptors that transport vitellogenin (VTG) into oocytes are of vital importance to egg-laying species because they mediate a key step in oocyte development. Here we describe the cloning of the first piscine oocyte-specific receptor cDNA, i.e., that encoding the VTG receptor from the rainbow trout (Oncorhynchus mykiss). The receptor, a 826-residue type-I membrane protein, is a member of the low density lipoprotein receptor (LDLR) superfamily. It closely resembles the mammalian so-called very low density lipoprotein receptors, in that its aminoterminal ligand binding domain consists of a cluster of 8 cysteine-rich repeats. The short intracellular portion contains the internalization signal typical for the LDLR superfamily, Phe-Glu-Asn-Pro-Val-Tyr. Notably, the receptor lacks a domain with a high density of potential O-glycosylation sites often found in somatic cell-specific members of the LDLR family. A specific transcript of 3.9 kb is abundant in ovary, but undetectable in muscle and heart, which are the major sites of expression of very low density lipoprotein receptors in mammals. In vitro translation of the full-length cDNA produced a 97-kDa protein, and transient expression in COS-1 cells showed that the cDNA encodes a protein of the same size that binds vitellogenin in ligand blots. As revealed by in situ hybridization, transcripts are present in previtellogenic oocytes, indicating that production of receptor protein precedes the phase of yolk deposition. Our results in fish, together with those in birds (Bujo, H., et al. 1994. EMBO J. 13: 5165-5175) suggest that vitelogenesis provides a prime model for the study of ligand/receptor systems designed to sustain reproduction.

Amino Acid Sequence↗
PubMed1990

Characterization of a second highly conserved B-type lamin present in cells previously thought to contain only a single B-type lamin.

Previous analyses of the nuclear lamina of mammalian cells have revealed three major protein components (lamins A, B and C) that have been identified by protein sequence homology as members of the intermediate filament (IF) protein family. It has been claimed that mammalian cells contain either all three lamins or lamin B alone. Using monoclonal antibodies specific for B-type lamins and cDNA cloning we identified a second major mammalian B-type lamin (murine lamin B2), thus showing that lamin composition in mammals is more complex than previously thought. Lamin B2 is coexpressed with lamin B1 (formerly termed lamin B) in all somatic cells and mammalian species that we analysed, including a variety of cells currently believed to contain only a single lamin. This suggests that two B-type lamins are necessary to form a functional lamina in mammalian somatic cells. By cDNA cloning we found that Xenopus laevis lamin LII is the amphibian homolog of mammalian lamin B2. Lamin expression during embryogenesis of amphibians and mammals shows striking similarities. The first lamins expressed in the early embryo are the two B-type lamins, while A-type lamins are only detected much later in development. These findings indicate that the genomic differentiation into two B-type lamins occurred early in vertebrate evolution and has been maintained in both their primary structure and pattern of expression.

Amino Acid Sequence↗
PubMed2005

Development of thermoregulation and torpor in a marsupial: energetic and evolutionary implications.

Altricial mammals and birds become endothermic at about half the size of adults and presumably would benefit energetically from entering torpor at that time. Because little is known about torpor during development in endotherms, we investigated whether after the establishment of endothermic thermoregulation (i.e. the ability to maintain a high body temperature during cold exposure), Sminthopsis macroura, a small (approximately 25 g) insectivorous marsupial, is capable of entering torpor and whether torpor patterns change with growth. Endothermic thermoregulation was established when the nest young reached a body mass of approximately 10 g, and they were capable of entering torpor early during development at approximately 10-12 g, lending some support to the view that torpor is a phylogenetically old mammalian trait. Torpor bout length shortened significantly and the minimum metabolic rate during torpor increased as juveniles approached adult size, and consequently total daily energy expenditure increased steeply with age. Relationships between total daily energy expenditure and body mass during development of S. macroura (slope approximately 1.3) differed substantially from the relationship between basal metabolism and body mass in adult endotherms (slope approximately 0.75) suggesting that the energy expenditure-size relationship during the development differs substantially from that in adults under thermo-neutral conditions. Our study shows that while torpor can substantially reduce energy expenditure during development of endotherms and hence is likely important for survival during energy bottlenecks, it also may enhance somatic growth when food is limited. We therefore hypothesize that torpor during the development in endotherms is far more widespread than is currently appreciated.

Animals↗
PubMed2003

Expressed murine and human CDR-H3 intervals of equal length exhibit distinct repertoires that differ in their amino acid composition and predicted range of structures.

Immunoglobulin junctional diversity is concentrated in the third complementarity-determining region of the heavy chain (CDR-H3), which often plays a dominant role in antigen binding. The range of CDR-H3 lengths in mouse is shorter than in human, and thus the murine repertoire could be presumed to be a subset of the human one. To test this presumption, we analyzed 4751 human and 2170 murine unique, functional, published CDR-H3 intervals. Although tyrosine, glycine, and serine were found to predominate in both species, the human sequences contained fewer tyrosine residues, more proline residues, and more hydrophobic residues (p<0.001, respectively). While changes in amino acid utilization as a function of CDR-H3 length followed similar trends in both species, murine and human CDR-H3 intervals of identical length were found to differ from each other. These differences reflect both divergence of germline diversity and joining gene sequence and somatic selection. Together, these factors promote the production of a rather uniform repertoire in mice of tyrosine-enriched CDR-H3 loops with stabilized hydrogen bond-ladders versus a much more diverse repertoire in human that contains CDR-H3 loops sculpted by the presence of intra-chain disulfide bonds due to germline-encoded cysteine residues as well as the enhanced presence of somatically generated proline residues that preclude hydrogen bond ladder formation. Thus, despite the presumed need to recognize a similar range of antigen epitopes, the murine CDR-H3 repertoire is clearly distinct from its human counterpart in its amino acid composition and its predicted range of structures. These findings represent a benchmark to which CDR-H3 repertoires can be compared to better characterize and understand the shaping of the CDR-H3 repertoire over evolution and during immune responses. This information may also be useful for the design of species-specific CDR-H3 sequences in synthetic antibody libraries.

Amino Acid Sequence↗
PubMed2000

Somatic mutations and aging: a re-evaluation.

Aging has been explained in terms of an accumulation of mutations in the genome of somatic cells, leading to tissue atrophy and neoplasms, as well as increased loss of function. Recent advances in transgenic mouse modeling and genomics technology have created, for the first time, the opportunity to begin testing this theory. In this paper the existing evidence for a possible role of somatic mutation accumulation in aging will be re-evaluated on the basis of the evolutionary logic of aging and recent insights in genome structure and function. New strategies for investigating the relationship between genome instability, mutation accumulation and aging will be discussed.

Aging↗
PubMed1997

What is the relationship between osteoarthritis and ageing?

The relationship between osteoarthritis and ageing raises important questions about what exactly defines 'normal' ageing and whether the pathogenesis of osteoarthritis shares common pathways with other age-associated dysfunctions, or whether osteoarthritis is a time-dependent disorder distinct from normal ageing with a separate causative mechanism at work. Theories of ageing now emphasize the stochastic nature of the ageing process, that is the role played by accumulation of essentially random cell and tissue damage, such as somatic mutations, oxidative damage and the formation of aberrant proteins. The role of genetic factors in determining longevity and predisposition to age-associated diseases is probably in programming the efficiency of somatic maintenance functions and in influencing the development of a durable soma. Gene-environment interactions, for example through lifestyle, can also be important. Many of the risk factors and mechanisms that are thought to contribute to osteoarthritis can be accommodated within this framework.

Aged↗
PubMed1989

Molecular dissection of a contiguous gene syndrome: frequent submicroscopic deletions, evolutionarily conserved sequences, and a hypomethylated "island" in the Miller-Dieker chromosome region.

The Miller-Dieker syndrome (MDS), composed of characteristic facial abnormalities and a severe neuronal migration disorder affecting the cerebral cortex, is caused by visible or submicroscopic deletions of chromosome band 17p13. Twelve anonymous DNA markers were tested against a panel of somatic cell hybrids containing 17p deletions from seven MDS patients. All patients, including three with normal karyotypes, are deleted for a variable set of 5-12 markers. Two highly polymorphic VNTR (variable number of tandem repeats) probes, YNZ22 and YNH37, are codeleted in all patients tested and make molecular diagnosis for this disorder feasible. By pulsed-field gel electrophoresis, YNZ22 and YNH37 were shown to be within 30 kilobases (kb) of each other. Cosmid clones containing both VNTR sequences were identified, and restriction mapping showed them to be less than 15 kb apart. Three overlapping cosmids spanning greater than 100 kb were completely deleted in all patients, providing a minimum estimate of the size of the MDS critical region. A hypomethylated island and evolutionarily conserved sequences were identified within this 100-kb region, indications of the presence of one or more expressed sequences potentially involved in the pathophysiology of this disorder. The conserved sequences were mapped to mouse chromosome 11 by using mouse-rat somatic cell hybrids, extending the remarkable homology between human chromosome 17 and mouse chromosome 11 by 30 centimorgans, into the 17p telomere region.

Biological Evolution↗
PubMed1993

Germ line maintenance of the pseudogene donor pool for somatic immunoglobulin gene conversion in chickens.

Somatic immunoglobulin diversity is generated in avian species by sequential gene conversion of variable (V) gene segments of the immunoglobulin heavy- and light-chain loci during B-cell development. The germ line pools of donor sequence information for somatic V-region gene conversion are found in families of V pseudogenes, located 5' of the single functional V gene of each locus. The sequence relationships among the pseudogenes (psi VL) and functional VL1 gene of the chicken light-chain alleles in three inbred strains were compared to determine the extent of diversity within the germ line pseudogene cluster. Numerous differences were observed. For example, compared with the previously reported CB allele and the G4 allele, the S3 allele contains two intact pseudogenes between psi VL16 and psi VL18. These two adjacent psi VL gene segments (psi VL17a and psi VL17b) could have given rise to the psi VL17 segment of the G4 and CB alleles by homologous recombination. The majority of other sequence polymorphisms among the psi VL alleles appear to be the result of meiotic gene conversion. The incidence of untemplated mutations within psi VL segments is significantly lower than the incidence of mutation within the pseudogene flanking regions. Together with the observations that most psi VL segments have open reading frames and lack stop codons, these data support the hypothesis that the psi VL cluster resembles a functional multigene family maintained by evolutionary selection for its functional role in generating somatic antibody diversity. Meiotic gene conversion events within the psi VL cluster serve both to introduce diversity by the exchange of short segments between family members and to prevent the accumulation of random mutations.

Alleles↗
PubMed1990

Mutations in the p53 gene are frequent in primary, resected non-small cell lung cancer. Lung Cancer Study Group.

The p53 gene has been implicated as a tumor suppressor gene with mutations found in common human cancers. We examined 51 early stage, primary, resected non-small cell lung cancer specimens using an RNAase protection assay and cDNA sequencing. Mutations changing the p53 coding sequence were found in 23/51 (45%) tumor specimens, but not in the corresponding normal lung, were distributed between codons 132 to 283, and included tumors with and without 17p allele loss. Fifteen of the 23 mutations lay in the predicted binding regions for SV40 large T antigen, and 14 were located in regions highly conserved between species. G to T transversions were a common result of p53 mutations in lung cancer compared to other cancers suggesting exposure to different mutagens. In univariate and multivariate analysis the presence of p53 mutations was associated with younger age and squamous histology. However, the presence of p53 mutations was not significantly associated with tumor stage, nodal status or sex and was found in all histologic types of lung cancer. We conclude that somatic mutations in the p53 gene play an important role in the pathogenesis of early stage non-small cell lung cancer.

Aged↗
PubMed1997

Somatic mutation theory, DNA repair rates, and the molecular epidemiology of p53 mutations.

The theory of somatic mutagenesis predicts that the frequency pattern of induced selectable mutations along a gene is the product of the probability patterns of the several sequential steps of mutagenesis, e.g., damage, repair, polymerase misreading, and selection. Together, the variance of these component steps is propagated to generate a mutagen's induced mutational spectrum along a gene. The step with the greatest component of variance will drive most of the variability of the mutation frequency along a gene. This most variable step, for UV-induced mutations, is the cyclobutyl pyrimidine dimer repair rate. The repair rate of cyclopyrimidine dimers is quite variable from nucleotide position to nucleotide position and we show that this variation along the p53 gene drives the C-->T transition frequency of non-melanocytic skin tumors. On showing that the kinetics of cyclopyrimidine dimer repair at any one nucleotide position are first order, we use this kinetic and the somatic mutation theory to derive Leq, the adduct frequency along a gene as presented to a DNA polymerase after a cell population reaches damage-repair equilibrium from a chronic dose of mutagen. Leq is the product of the first two sequential steps of mutagenesis, damage and repair, and the frequency of this product is experimentally mapped using ligation-mediated PCR. The concept of Leq is applied to mutagenesis theory, chronic dose genetic toxicology, genome evolution, and the practical problems of molecular epidemiology.

Animals↗
PubMedDate not supplied

[Typology of elderly patients hospitalized in psychiatry: evaluation of psychiatric antecedents before age 60].

To take care of elderly patients in psychiatric hospital sets specific problems. It is interesting to know the mode, the frequency, and the reasons of these hospitalizations, to improve the medical care given to these subjects. We made a prospective study with elderly patients hospitalized in a psychiatric institution. The results were completed in discussions with the medical care staff. During the study (January and February 1997), 112 elderly patients, about more than 60 years old, were hospitalized in Villejuif' specialized hospital (inpsychiatric units). Informations about social facts, main psychiatric previous, reasons of the hospitalization, the caring and the evolution of these subjects were collected. The main important reflexion we did observe was the significant difference between elderly patients hospitalized in psychiatric units, with or without psychiatric previous before the age of 60. Those who were hospitalized at the first time in psychiatric units before 60, presented a medium aged population, younger than the other group. They also presented more delusion with psychosis, were more frequently hospitalized longly in psychiatric units, took neuroleptics, and their somatic associate pathologies were less difficult to take care of. In the second group including the elderly patients without psychiatric previous before 60, we did observe very different characteristics: the diagnosis of most of the patients is dementia; these elderly subjects leaved mostly at home, they presented more sadness, aggression, or social inappropriate behaviour. Depression is a more frequent diagnosis. This study of all the elderly patients admitted in a psychiatric hospital confirmed the population's heterogeneity. The existence of an hospitalisation in psychiatric unit before sixty represented a pertinent test to a major and simple approach of these differences. The psychiatric unit which receives more and more elderly patients take care of their differences to the organisation of care needs between the gerontopsychiatric patients types. The patients with a late gerontopsychiatric's disease could need a specific hospitalization in gerontopsychiatric units, especially organised to deliver psychiatric cares and somatic cares, including medical geriatric practicer and medical care staff formed to the dependence need care.

Aged↗
PubMedDate not supplied

[Pilot study comparing in blind the therapeutic effect of two doses of agomelatine, melatoninergic agonist and selective 5HT2C receptors antagonist, in the treatment of major depressive disorders].

Rational and method - Two doses of agomelatine (S-20098), a novel potential antidepressant drug with a new pharmacological profile (melatonin agonist and selective 5HT2C antagonist -MASSA), were compared in a double-blind, randomised, pilot study in order to estimate the antidepressant activity shown in preclinical data. Inpatients suffering from major depressive disorder (DSM III-R criteria) and presenting a minimal score of 25 for MADRS were selected at D -7. After one week of run-in placebo treatment, included patients received one evening dose of agomelatine (either 5 or 100 mg) for 4 to 8 weeks. Hospitalization was required at least for the first 3 weeks. Patients presenting a satisfying response to treatment (MADRS total score<15 or decrease 40% from inclusion score) could be treated as outpatients. A follow up of 2 weeks was performed after stopping the treatment. The total duration of the treatment period could vary, according to investigator's decision, between 7 and 11 weeks. Evaluation criteria included MADRS, HAMD-17, HAM-A, CGI and AMDP 5 at D0, D7, D14 and D28, and, when applicable, at D35, D42, D49 and D56. Safety evaluations included recording of adverse events, ECG monitoring and biology. Results - Thirty inpatients were selected and 28 included (14 per group). There was no major difference between groups at inclusion, neither for demographic nor evaluation criteria. One patient of each group was excluded of the ITT analysis; 19 patients completed the mandatory period up to D28: 10 in the 5 mg group and 9 in the 100 mg group; 10 patients (5 in each group) carried on the study during the optional period, up to D56 for 7 out of them (4 in the 5 mg group, 3 in the 100 mg group). Efficacy criteria showed a significant improvement in both groups, with highly significant within group evolutions (p<0.001 whatever the criteria) and without significant difference between groups. However, better results were observed in the 5 mg group compared to the 100 mg group. Total MADRS scores then decreased from 30.7 3.5 to 14.8 6.4 in the 5 mg group vs a decrease from 31.6 4.7 to 18.6 14.8 in the 100 mg group. Furthermore, significant improvement between D14 and D28 visits were only seen in the 5 mg group. Analysis of somatic complaints (AMDP 5) showed with both treatment a strong decrease of symptoms during the study, especially for items related to sleep disorders (difficulties for falling asleep, interrupted sleep, shortened sleep, early wakening and drowsiness). Acceptability was good for both doses of agomelatine. However, there were slightly more emergent adverse events and severe treatment-related adverse event in the 100 mg group. No modifications of cardio-vascular parameters nor biological abnormalities were observed in both groups. Conclusion - Preliminary clinical data with agomelatine confirm the potential antidepressant effect in accordance with positive preclinical results. There was no significant difference between 5 and 100 mg, both for efficacy and for safety. However, the data suggest that 5 mg could be a at least as effective and slightly better tolerated dose than 100 mg. Further double-blind controlled studies versus active comparators and placebo are required in order to confirm these results.

Acetamides↗
PubMedDate not supplied

[Pilot study comparing in blind the therapeutic effect of two doses of agomelatine, melatonin- agonist and selective 5HT2c receptors antagonist, in the treatment of major depressive disorders].

RATIONALE AND METHOD: Two doses of agomelatine (S-20098), a novel potential antidepressant drug with a new pharmacological profile (melatonin agonist and selective 5HT2C antagonist), were compared in a double-blind, randomised, pilot study in order to estimate the antidepressant activity shown in preclinical data. Inpatients suffering from major depressive disorder (DSM III-R criteria) and presenting a minimal score of 25 for MADRS were selected at D-7. After one week of run-in placebo treatment, included patients received one evening dose of agomelatine (either 5 or 100 mg) for 4 to 8 weeks. Hospitalization was required at least for the first 3 weeks. Patients presenting a satisfying response to treatment (MADRS total score < 15 or decrease > or = 40% from inclusion score) could be treated as outpatients. A follow up of 2 weeks was performed after stopping the treatment. The total duration of the treatment period could vary, according to investigator's decision, between 7 and 11 weeks. Evaluation criteria included MADRS, HAMD-17, HAM-A, CGI and AMDP 5 at D0, D7, D14 and D28, and, when applicable, at D35, D42, D49 and D56. Safety evaluations included recording of adverse events, ECG monitoring and biology. RESULTS: Thirty inpatients were selected and 28 included (14 per group). There was no major difference between groups at inclusion, neither for demographic nor evaluation criteria. One patient of each group was excluded of the ITT analysis; 19 patients completed the mandatory period up to D28: 10 in the 5 mg group and 9 in the 100 mg group; 10 patients (5 in each group) carried on the study during the optional period, up to D56 for 7 out of them (4 in the 5 mg group, 3 in the 100 mg group). Efficacy criteria showed a significant improvement in both groups, with highly significant within group evolutions (p < 0.001 whatever the criteria) and without significant difference between groups. However, better results were observed in the 5 mg group compared to the 100 mg group. Total MADRS scores then decreased from 30.7 +/- 3.5 to 14.8 +/- 6.4 in the 5 mg group vs a decrease from 31.6 +/- 4.7 to 18.6 +/- 14.8 in the 100 mg group. Furthermore, significant improvement between D14 and D28 visits were only seen in the 5 mg group. Analysis of somatic complaints (AMDP 5) showed with both treatments a strong decrease of symptoms during the study, especially for items related to sleep disorders (difficulties in falling asleep, interrupted sleep, shortened sleep, early wakening and drowsiness). Acceptability was good for both doses of agomelatine. However, there were slightly more emergent adverse events and severe treatment-related adverse events in the 100 mg group. No modifications of cardio-vascular parameters nor biological abnormalities were observed in both groups. CONCLUSION: Preliminary clinical data with agomelatine confirm the potential antidepressant effect in accordance with positive preclinical results. There was no significant difference between 5 and 100 mg, both for efficacy and for safety. However, the data suggest that 5 mg could be a dose at least as effective and slightly better tolerated than 100 mg. Further double-blind controlled studies versus active comparators and placebo are required in order to confirm these results.

Acetamides↗
PubMed1988

Alteration and abnormal expression of the c-myc oncogene in human multiple myeloma.

Structural alterations of the c-myc oncogene in human Burkitt's lymphoma and mouse plasmacytoma suggest that this oncogene is involved in several B cell neoplasms. The possibility of c-myc alterations in human myeloma has not been explored, probably because the low proliferative activity characteristic of this tumor impairs the propagation of representative cell lines for the performance of adequate cytogenetic studies. This report describes alterations in the c-myc locus with concomitant elevated expression of mRNA in the tumor cells of two of 37 patients with multiple myeloma. In one case, somatic cell hybrid studies revealed that the cloned rearranged DNA was entirely derived from chromosome 8, thus indicating a novel mechanism of c-myc activation different from that in Burkitt's lymphoma. Seven other patients exhibited five- to 12-fold overexpression of c-myc RNA when compared with normal marrow cells. Elevated mRNA expression in about one fourth of our patients suggests that the c-myc oncogene has a pathogenetic role in the evolution of multiple myeloma.

Animals↗
PubMed1975

The primary structure of a rat kappa Bence Jones protein: phylogenetic relationships of V- and C-region genes.

The complete amino acid sequence of a LOU rat k Bence Jones protein, S211, is presented. The availability of such a sequence makes it possible to re-evaluate the phylogenetic relationships of V- and C-region genes. The data suggest that V- and C-genes, and also V-genes between themselves have evolved at different rates. The Vk1-gene seems to have been preserved during evolution and its products could be identified in three other species. The differences between these Vk1 representative sequence are similar and fall inside the range of inter-subgroup differences. On the other hand, the comparison of Ck-regions from four different species agrees with their recognized phylogenetic relationships. Evidence is presented which suggests that two substitutions within the C-region of the S211 k-chain are unrelated to allotypes and presumably represent somatic events or are evidence for multiple isotypes of rat Ck-region.

Amino Acid Sequence↗
PubMed2006

Significance of somatic mutations and content alteration of mitochondrial DNA in esophageal cancer.

BACKGROUND: The roles of mitochondria in energy metabolism, the generation of ROS, aging, and the initiation of apoptosis have implicated their importance in tumorigenesis. In this study we aim to establish the mutation spectrum and to understand the role of somatic mtDNA mutations in esophageal cancer. METHODS: The entire mitochondrial genome was screened for somatic mutations in 20 pairs (18 esophageal squamous cell carcinomas, one adenosquamous carcinoma and one adenocarcinoma) of tumor/surrounding normal tissue of esophageal cancers, using temporal temperature gradient gel electrophoresis (TTGE), followed by direct DNA sequencing to identify the mutations. RESULTS: Fourteen somatic mtDNA mutations were identified in 55% (11/20) of tumors analyzed, including 2 novel missense mutations and a frameshift mutation in ND4L, ATP6 subunit, and ND4 genes respectively. Nine mutations (64%) were in the D-loop region. Numerous germline variations were found, at least 10 of them were novel and five were missense mutations, some of them occurred in evolutionarily conserved domains. Using real-time quantitative PCR analysis, the mtDNA content was found to increase in some tumors and decrease in others. Analysis of molecular and other clinicopathological findings does not reveal significant correlation between somatic mtDNA mutations and mtDNA content, or between mtDNA content and metastatic status. CONCLUSION: Our results demonstrate that somatic mtDNA mutations in esophageal cancers are frequent. Some missense and frameshift mutations may play an important role in the tumorigenesis of esophageal carcinoma. More extensive biochemical and molecular studies will be necessary to determine the pathological significance of these somatic mutations.

Adenocarcinoma↗
PubMed1987

Parasexual analysis of human pepsinogen molecular heterogeneity.

Pepsinogens (PGA) are the inactive precursors of pepsin, the major acid protease found in the stomach. Highly polymorphic variation of these proteins has been demonstrated in several populations, and comparison of the DNA restriction fragment patterns obtained from informative pepsinogen phenotypes suggest that the polymorphism results from chromosomal haplotypes containing variable numbers of pepsinogen genes. In order to isolate the three most common PGA haplotypes (A, B, and C) and to unambiguously demonstrate their relationship to the observed protein heterogeneity, we constructed mouse X human somatic cell hybrids from individuals heterozygous for PGA and INS (insulin). Here, we describe analysis of hybrid cell lines that segregated human chromosomes containing the PGA genes and thereby provided for the parasexual discrimination of the different haplotypes on chromosome 11 determining the corresponding heterozygous phenotypes. These studies demonstrate that the A, B, and C haplotypes contain three, two, and one PGA genes, respectively. This unusual polymorphism of genomic DNA encoding very similar proteins probably reflects recent evolution by gene duplication.

Animals↗
PubMed2001

Molecular signals versus the Loi de Balancement.

Life history tradeoffs are often thought to be caused by the allocation of limited resources among competing traits such as reproduction, somatic growth and maintenance. One line of evidence supporting this comes from eliminating reproduction, for example, by surgically removing gonads. However, recent evidence from the nematode Caenorhabditis elegans suggests that the apparent tradeoffs it shows might not be due to resource allocation at all but rather to the effects of a molecular signal originating in the germ line that represses longevity. These results should cause us to rethink the interpretation of many classic experiments in life history evolution.

Journal Article↗