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At least 271 records · Page 15Linked to original sources

Clonal evolution in human lymphoblast cultures.

We established lymphoblast cultures from normal females heterozygous for electrophoretic variants of glucose-6-phosphate dehydrogenase (G6PD), and the X-linked markers have permitted us to look at evolution of these cell populations in culture. The established cultures were phenotypically heterozygous at onset, having both of the mosaic cell populations resulting from X chromosome inactivation. However, by the tenth subculture, the population of cells no longer reflected the heterozygous genotype in 50% of the cultures, as only a single G6PD isozyme was expressed. The ultimate cell composition seems to be influenced by the initial composition, by the nature of alleles at heterozygous X-linked loci that may provide a growth advantage (or disadvantage), as well as by stochastic events. Our results show that lymphoblast cultures may not reflect the X-linked phenotype of the cells from which they were derived. The fate of such cultures seems to be evolution toward clonal cell populations.

Cells, Cultured↗

The importance of cultural inheritance in psychiatric genetics.

Cultural inheritance, a genetic-based inheritance system transmitted by the brain, has previously been proposed to underlie normal behaviour and mental disorders. In cultural inheritance epigenetic mechanisms are involved in gene expression. This paper proposes that since there are marked epigenetic mechanisms involved in the expression of genes underlying primary (idiopathic) mental disorders, epimutations, rather than genetic mutations, underlie these disorders.

Animals↗

Sociality, age at first reproduction and senescence: comparative analyses of birds.

Evolutionary theories of senescence suggest that aging evolves as a consequence of early reproduction imposing later viability costs, or as a consequence of weak selection against mutations that act late in life. In addition, highly social species that live in sites that are protected from extrinsic mortality due to predation should senesce at a slower rate than solitary species. Therefore, species that start reproducing late in life should senesce at a slower rate than species that start reproducing early. In addition, social species should senesce more slowly than solitary species. Here I investigate the rate of senescence using an extensive data set on longevity records under natural field conditions to test predictions about the evolution of senescence among 271 species of birds. Longevity records increased with sampling effort and body mass, but once these confounding variables were controlled statistically, there was a strongly positive relationship between relative longevity and relative adult survival rate. Relative longevity after controlling statistically for sampling effort, body mass and adult survival rate, increased with age at first reproduction, but not with degree of breeding sociality. These findings suggest that the evolution of senescence is related to timing of first reproduction, but that the evolution of breeding sociality has played a negligible role in the evolution of senescence.

Aging↗

Karyotypic evolution of cells in culture: a new concept.

The Chapter summarizes peculiarities of karyotypic variability during establishment and long-term cultivation of permanent cell lines. A new concept on pathways of karyotypic evolution of cells in culture is put forward. A detailed description is presented of the author's original approach of cytogenetic analysis of cell lines provided for a principally new characteristic of the cell line: its generalized reconstructed karyotype (GRK). Its use as a criterion to evaluate authenticity, purity, and stability of cell lines is discussed. Based on analysis of the GRK, two stages of karyotype evolution of cell lines are revealed: establishment and stabilization, different in karyotypic variability of the cell population and in peculiarities of clone selection. Comparison of peculiarities of karyotypic variability of leukemic and tumor cells both in vitro and in vivo was made, and general regularities of their karyotypic evolution have been established, such as nonrandom changes in the number and structure of chromosomes and deletion of one of the sex chromosomes, as well as regularities characteristic only of cells in culture in most human and animal cell lines (at least 85%) of disomy on all autosomes. The rest of the cell lines, 15%, are characterized by either partial or total monosomies on certain autosomes during long-term cultivation. Three main compensatory mechanisms of maintaining viability of cell lines that have lost genetic material are discussed: polyploidization of the initial cell clone, amplification of oncogenes (predominantly of mys family), and extracopying of whole autosomes or of their fragments.

Animals↗

Expression of glucose transporters (GLUT 1 and GLUT 4) in primary cultured rat adipocytes: differential evolution with time and chronic insulin effect.

We previously reported that in cultured adipose cell lines insulin increased selectively the expression of Glut 1, in contrast to in vivo regulation where variations in insulinemia have been shown to affect only GLUT 4. We have addressed here the question of the long-term regulation of GLUT 1 and GLUT 4 in fat cells by using primary cultures of rat adipocytes. Epididymal fat cells were isolated by collagenase and cultured 4 days in DMEM supplemented with BSA 1%, FCS 1%, and glucose 10 mM. GLUT 1 and GLUT 4 proteins were assessed in total cellular membranes by Western blotting, using specific antibodies against their respective C-terminal peptides. GLUT 1 steadily increased over culture time to reach at day 3, a level 3-fold higher than the initial value. In contrast, GLUT 4 decreased sharply and stabilized at day 3, at 30% of the initial value. The changes in GLUT 1 and GLUT 4 mRNAs with culture time were parallel to changes in the corresponding proteins, suggesting a pre-translational level of regulation. The expression of the lipogenic enzyme, fatty acid synthetase (FAS), highly expressed in fat cell, decreased over time following a pattern closely parallel to that of GLUT 4. Chronic exposure to insulin added at day 2 had no effect on GLUT 4 expression but increased the expression of GLUT 1 and FAS by 70% and 36%, respectively. Glucose consumption was stable over 4 days of culture, while lactate production increased from 24 to 36% of glucose utilization, in agreement with the loss in FAS. Glucose consumption increased only slightly with insulin (+160%), in good keeping with the low levels of expression of both GLUT 4 and FAS in these cultured cells. These data indicate that culture alters oppositely the expression of GLUT 1 and GLUT 4 in rat adipocytes and suggest that factor(s) other than insulin predominate in their regulation in vivo.

Adipose Tissue↗

A stochastic model of gene-culture coevolution suggested by the "culture historical hypothesis" for the evolution of adult lactose absorption in humans.

A stochastic model of gene-culture coevolution, suggested by the "culture historical hypothesis" of Simoons and McCracken, is presented. According to this hypothesis, adult lactose absorption, believed to be an autosomal dominant trait, attained a high frequency in some human populations due to the positive selection pressure induced by culturally determined milk use in those populations. Two-dimensional Kolmogorov backward equations with appropriate boundary conditions are derived for the ultimate fixation probability of milk users, of the gene for adult lactose absorption, and of both jointly, and for the average time until fixation of the gene. These boundary value problems are solved numerically by the Gauss-Seidel method. I define a theoretical measure of the correlation between gene and culture in terms of the three ultimate fixation probabilities. Monte Carlo simulations are conducted to check and extend the numerical results and also to obtain the first arrival time at gene frequency 0.70, which is approximately the highest observed frequency in any population. Two results that pertain to the culture historical hypothesis are obtained. First, the incomplete correlation observed between adult lactose absorption and milk use does not necessarily constitute evidence against the hypothesis. Second, for the postulated genetic change to have occurred within the 6000-year period since the advent of dairying, either the effective population size was of the order of 100, or, if it was of larger order, the selection coefficient probably had to exceed 5%.

Animals↗