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Divergent selection for mature body weight in dwarf White Leghorns. 1. Growth and reproductive responses to selection.

Genetic selection for high (H) and low (L) 20-week body weight (BW) in dwarf White Leghorns was practiced for three generations. The base population was the Oregon State University dwarf Leghorn population (C) selected previously for part year hen-housed egg production (EP), early sexual maturity (SM), and large initial egg weight (EW). Asymmetry of response was observed in both sexes. Realized heritabilities for 20-week BW for H and L males were .49 and .36 and for H and L females were .45 and .79, respectively. Twenty-week BW of the 3rd generation H and L line females were 1.48 and .80 kg, respectively, compared to 1.13 kg for the C line. Similar weights for the males were 1.74, .97, and 1.27 kg for the H, L, and C line, respectively. The H and L lines diverged significantly in 10, 20, 40, and 60-week BW, SM, and EW after one generation of selection and the divergence continued through the third generation. The EP and egg specific gravity did not differ among lines. The C line was intermediate to the selected lines for all traits except EP. The EW at 35 and 60 weeks differed between the H and L lines by 10 g at generation 3 and SM was 149 and 157 days for the H and L lines, respectively.

Animals↗

Genetic selection of homozygote allozyme genotypes in marine gastropods exposed to cadmium pollution.

Five species of marine gastropods (Monodonta turbinata, M. turbiformis, Cerithium scabridum, Littorina punctata and L. neritoides) were exposed to cadmium in the laboratory. The enzyme phosphoglucose isomerase (PGI) tested electrophoretically showed for all five species a statistically significant higher proportion of heterozygotes among the dead animals than among the survivors in the range of concentration tested. This pattern seems to have been established by natural selection. Further, it could be used in developing biological monitors of present and past cadmium pollution based on the genetic response of natural populations to this specific pollutant.

Animals↗

Effect of the genetic selection of turkeys for increased body weight and egg production on immune and physiological responses.

Selection of poultry for fast growth rate is often accompanied by a reduction in specific immune responses or increased disease susceptibility. In this study, 17-wk-old male turkeys from each of four closed genetic lines, a randombred control (RBC) line and its subline (F) selected for increased 16-wk BW, and another RBC and its subline (E) selected for increased egg production, were tested for in vivo response to toe web inoculation with phytohemagglutinin-P (PHA-P), in vitro response of lymphocytes in whole blood to PHA-P and concanavalin A (Con A), hemolytic complement activity, differential white blood cell counts, hematology, and serum chemistry values. Fifteen male turkeys from each of two commercial lines, Com A and Com B, were also tested. The large-bodied F line birds had a lower toe web response to PHA-P, lower lymphocyte counts, and lower relative spleen weights than their smaller parent line. Body weights, total erythrocyte counts, blood urea nitrogen (BUN) levels, and in vitro mitogenic response to PHA-P and Con A were higher in the F line birds. Line E had lower hemolytic complement levels, lower relative spleen and relative bursal weights, and a higher in vitro mitogenic response to PHA-P than its parent line. The Com B line had a lower toe web response to PHA-P, and lower serum levels of gamma-glutamyltransferase and bilirubin than Com A. Line Com B had higher total RBC counts and higher levels of alanine aminotransferase (ALT) than Com A. These results support the concept that some changes in the cell-mediated immune response, as well as other physiological changes that may potentially affect immune response, appear to accompany selection for faster growth.

Alanine Transaminase↗

Studies on relationships between metastatic and non-metastatic tumor cell populations using lineages labeled with dominant selectable genetic markers.

The relationships between metastatic and non-metastatic cell populations co-existing in composite neoplasms have been studied using cell lineages marked with a dominant selectable marker (neomycin resistance), by transfection. The experimental circumstances were arranged so that the lineages were known to be genotypically distinct (i.e. not merely phenotypic variants of the same lineage) and so that a single metastatic clone was each time combined with a mixed polyclonal non-metastatic population and both partners were distinctly and recognizably marked. This made it possible to ascertain the fates of clones with different metastatic capabilities during tumor progression and metastasis and evaluate their relative contributions to the clinical extent of disease. It was found that metastatic and non-metastatic cell lineages co-existed in most of the late-stage primary tumors examined and that a cell lineage that is invariably non-metastatic, when growing on its own, can with surprising frequency be found thriving in distant metastatic deposits, when it grows to form a primary tumor in combination with a metastatic partner. In fact, occasional metastases from such tumors contained no detectable cells of the metastatic lineage. The endowment of a tumor cell lineage with a new, clinically significant, capability which it convincingly and reproducibly did not manifest before, by another coexisting cell population raises several new questions about the contribution of such phenomena to the overall debilitating properties of the neoplasm and the geometric progression of its impact on the host.

Animals↗

Genetic selection of regulatory mutants of mammalian adenylyl cyclases.

Initial steps in the identification of the Gs alpha-binding site present in mammalian adenylyl cyclases can be achieved with the use of the yeast genetic system described. It must be stressed that this system serves as a means to identify mutants that are candidates; biochemical analysis of these mutants is a next and necessary step in the confirmation of these phenotypes. The system described can be readily adapted for the isolation of additional classes of mammalian adenylyl cyclase mutants including mutants with altered regulation toward forskolin, catalytic abnormalities, or enhanced sensitivities toward activators. In addition, this system can be employed for the isolation of constitutively active adenylyl cyclase mutants, or by coexpressing other adenylyl cyclase isoforms and their known regulators, mutations in the binding sites for these molecules can be elucidated.

Adenylyl Cyclases↗

Genetic selection for avoidance behavior in the rat.

Long-Evans rats were selectively bred for over 20 generations using two behavioral criteria: (1) limited responding to the warning signal during ten pretest trials and (2) either good or poor avoidance behavior during 60 avoidance training trials in a two-way shuttlebox. The results suggest that avoidance behavior in the rat is a heritable characteristic that may be selected independently of activity level.

Animals↗

Effect of genetic selection for milk yield and increased milking frequency on plasma growth hormone and prolactin concentration in Holstein cows.

Fifty Holstein cattle, either second to fourth generation daughters of cows randomly bred to non-commercial sires originating in the Virginia Tech dairy herd (estimated mean PDM84 = -455 kg, control animals), or daughters of cows bred to commercially available sires (mean PDM84 = +368 kg, selection animals), were randomly assigned to be milked twice or thrice daily starting at parturition. Serial blood samples were collected via jugular cannulae at 30, 90 and 200 d post-partum (DPP) during both the first and second lactations. Blood samples were collected for 3 h prior to and 4 h following thyrotropin releasing hormone (TRH) administration, and were analyzed for growth hormone (GH) and prolactin (PRL) concentrations. Dry matter intake, body weight and milk yield and fat content were used to calculate net energy balance (NEB) of animals at each DPP sampling period. Mean plasma GH concentrations were greater (P less than .01) in selection vs control animals both before and after TRH administration, and decreased (P less than .01) with advancing lactation (30 greater than 90 greater than 200 DPP). However, NEB was not influenced by genetic merit, implying that observed differences in GH concentrations were not due to that trait. Plasma PRL concentrations were not affected by genetic merit or DPP, but were greater (P less than .01) in the second vs first lactation. Neither PRL or GH concentrations were affected by frequency of milking. The results support the contention that increased plasma GH concentrations are associated with selection for increased milk yield.

Animals↗

Genetic selection of peptide aptamers that recognize and inhibit cyclin-dependent kinase 2.

A network of interacting proteins controls the activity of cyclin-dependent kinase 2 (Cdk2) (refs 1,2) and governs the entry of higher eukaryotic cells into S phase. Analysis of this and other genetic regulatory networks would be facilitated by intracellular reagents that recognize specific targets and inhibit specific network connections. We report here the expression of a combinatorial library of constrained 20-residue peptides displayed by the active-site loop of Escherichia coli thioredoxin, and the use of a two-hybrid system to select those that bind human Cdk2. These peptide aptamers were designed to mimic the recognition function of the complementarity-determining regions of immunoglobulins. The aptamers recognized different epitopes on the Cdk2 surface with equilibrium dissociation constant in the nanomolar range; those tested inhibited Cdk2 activity. Our results show that peptide aptamers bear some analogies with monoclonal antibodies, with the advantages that they are isolated together with their coding genes, that their small size should allow their structures to be solved, and that they are designated to function inside cells.

Amino Acid Sequence↗

In vitro immune response of spleen cells from mice genetically selected for high or low antibody production.

The aim of this study was the identification of the cell type in which genes selected for high or low response to SRBC express their functions. Spleen cells from high (H) and low (L) responder mice were immunized with SRBC in the Mishell and Dutton system. An antibody response of different magnitude was found in cultures of H and L spleen cells, the difference being at least as great as that observed in vivo. This finding under experimental conditions allowing the exclusion of any influence of the animal milieu during the immune response, suggest macrophages, B, and T lymphocytes as possible target cells of gene action. In vitro cell separation and recombination experiments in which spleen cells were immunized with SRBC, TNP-LPS, or TNP-HRBC indicate that the genetic differences between H and L responders brought about by selective breeding are expressed in lymphocytes to greater extent than in macrophages. The role of histoincompatibility in the recombination experiments in unlikely but cannot be excluded. Among lymphocytes, B cells but not helper T cells were found more responsive in cultures of spleen cells from H than from L mice.

Animals↗

Rabies virus immunity in genetically selected high- and low-responder lines of mice.

The antibody responsiveness to and the specific vaccination effect of rabies virus infection were investigated in high- and low-responder lines of mice produced by two-way selective breedings for quantitative production of antibodies to flagellar (H/f and L/f lines) or somatic (H/s and L/s lines) antigens of salmonellae. After specific immunization, both high lines were more resistant to rabies virus infection than were the low lines, and the protector effect was related to the level of antibody produced, as demonstrated by neutralizing serum activity. The present findings confirm the nonspecific genetic modification of the general antibody responsiveness induced in high- and low-responder lines selected for quantitative antibody production.

Animals↗