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PubMed2006

One-step selection of artificial transcription factors using an in vivo screening system.

Gene expression is regulated in large part at the level of transcription under the control of sequence-specific transcriptional regulatory proteins. Therefore, the ability to affect gene expression at will using sequence-specific artificial transcription factors would provide researchers with a powerful tool for biotechnology research and drug discovery. Previously, we isolated 56 novel sequence-specific DNA-binding domains from the human genome by in vivo selection. We hypothesized that these domains might be more useful for regulating gene expression in higher eukaryotic cells than those selected in vitro using phage display. However, an unpredictable factor, termed the "context effect", is associated with the construction of novel zinc finger transcription factors--- DNA-binding proteins that bind specifically to 9-base pair target sequences. In this study, we directly selected active artificial zinc finger proteins from a zinc finger protein library. Direct in vivo selection of constituents of a zinc finger protein library may be an efficient method for isolating multi-finger DNA binding proteins while avoiding the context effect.

Cells, Cultured↗
PubMed1976

Selection for agonistic begavior in wild female Mus musculus.

Artificial selection was used to establish different levels of agonistic behavior in laboratory-reared wild female Mus musculus. A within-family selection design with replicated high and low lines and two nonselected control lines was employed. Females only were tested at 8 weeks of age on 2 consecutive days. Testing consisted of placing a C57BL/6 female mouse in the home cage of the isolation-reared wild mouse for 7 min or until an attack occurred. The wild females were rated on a 5-point scale for agonistic behavior, and the sum of the scores over the 2 test days was the criterion for selection. The six lines, each containing ten breeding pairs, were selected for four generations. By the fourth selected generation, the responses of the high and low lines had diverged in the expected directions. One-way analyses of variance indicated reliable differences among high, low, and control lines in the second, third, and fourth generations. It was concluded that female agonistic behavior is influenced by genotype and that the level of this behavior can be manipulated by means of artificial selection.

Age Factors↗
PubMed1999

Correlated responses to selection on body size in Drosophila melanogaster.

Correlated responses to artificial selection on body size in Drosophila melanogaster were investigated, to determine how the changes in size were produced during development. Selection for increased thorax length was associated with an increase in larval development time, an extended growth period, no change in growth rate, and an increased critical larval weight for pupariation. Selection for reduced thorax length was associated with reduced growth rate, no change in duration of larval development and a reduced critical larval weight for pupariation. In both lines selected for thorax length and lines selected for wing area, total body size changed in the same direction as the artificially selected trait. In large selection lines of both types, the increase in size was achieved almost entirely by an increase in cell number, while in the small lines the decrease in size was achieved predominantly by reduced cell size, and also by a reduction in cell number. The implications of the results for evolutionary-genetic change in body size in nature are discussed.

Animals↗
PubMed2001

Polyandry in Lepidoptera: a heritable trait in Spodoptera exigua Hübner.

The genetic basis as well as the mode of inheritance of polyandry in Spodoptera exigua Hübner was studied in the laboratory by using a simple divergent selection experiment followed by F1 reciprocal crosses, F2 and backcrosses. There was an effective response to artificial selection for high (H line) and low (L line) female mating frequency with significant separation of the lines by the second generation of selection. The mean female mating frequency in the parental generation (1.57 matings per female) reached plateaus of 2.50 and 1.25 matings per female in the H and L lines, respectively, after six generations of selection. Selection response becomes saturated at about 90% and 25% levels of polyandry (percentage females re-mating) in the H and L lines, respectively, and consequently mono- and polyandric pure strains were not obtained. Polyandry levels in offspring from the H and L lines and their hybrids in F1, F2 and backcrosses consistently indicate that female mating frequency was more or less proportional to the relative amounts of genes derived from the H and L lines. Such a clear pattern of hybrid responses, together with the gradual selective changes under artificial selection, suggests the involvement of a polygenic system. Female mating frequencies from progeny of the two reciprocal F1 crosses were not significantly different, which suggest that the trait was autosomally inherited. Moreover, female mating frequency of F1 (pooled) progeny was not significantly different from the mid-parental value, which suggest no dominance. The computation of the Cavalli's joint scaling test consistently confirmed these results yielding values of d = 0.51 +/- 0.10 and h = 0.12 +/- 0.21. The broad sense heritability estimate was H2 = 0.73. It is concluded that polyandry in S. exigua is a polygenic, autosomal heritable trait and that additive genetic variance is available for selection for female mating frequency. The implications of the genetic basis of polyandry are briefly discussed in the context of current theories about this crucial insect mating system.

Animals↗
PubMed2004

Artificial genetic selection for an efficient translation initiation site for expression of human RACK1 gene in Escherichia coli.

In bacterial expression systems, translation initiation is usually the rate limiting and the least predictable stage of protein synthesis. Efficiency of a translation initiation site can vary dramatically depending on the sequence context. This is why many standard expression vectors provide very poor expression levels of some genes. This notion persuaded us to develop an artificial genetic selection protocol, which allows one to find for a given target gene an individual efficient ribosome binding site from a random pool. In order to create Darwinian pressure necessary for the genetic selection, we designed a system based on translational coupling, in which microorganism survival in the presence of antibiotic depends on expression of the target gene, while putting no special requirements on this gene. Using this system we obtained superproducing constructs for the human protein RACK1 (receptor for activated C kinase).

Drug Resistance, Bacterial↗
PubMed1990

Efficiency of marker-assisted selection in the improvement of quantitative traits.

Molecular genetics can be integrated with traditional methods of artificial selection on phenotypes by applying marker-assisted selection (MAS). We derive selection indices that maximize the rate of improvement in quantitative characters under different schemes of MAS combining information on molecular genetic polymorphisms (marker loci) with data on phenotypic variation among individuals (and their relatives). We also analyze statistical limitations on the efficiency of MAS, including the detectability of associations between marker loci and quantitative trait loci, and sampling errors in estimating the weighting coefficients in the selection index. The efficiency of artificial selection can be increased substantially using MAS following hybridization of selected lines. This requires initially scoring genotypes at a few hundred molecular marker loci, as well as phenotypic traits, on a few hundred to a few thousand individuals; the number of marker loci scored can be greatly reduced in later generations. The increase in selection efficiency from the use of marker loci, and the sample sizes necessary to achieve them, depend on the genetic parameters and the selection scheme.

Animals↗
PubMed1998

Sex-specific selection on time to remate in Drosophila melanogaster.

Female Drosophila melanogaster were artificially selected for fast and slow time to remate (denoted 'high' and 'low' selection regimes, respectively). Both selection regimes and a control were replicated three times. Correlated responses to selection in females and in males were measured. A significant direct response to selection for time to remating was found in females from both selection regimes. Remating frequency of females showed a correlated response only in the females from the lines selected for faster time to remating. Time to first mating of virgin females showed no correlated response in either selection regime. No correlated response was found in males for time to remate, remating frequency or time to first mating of virgins, indicating that genetic correlations between the sexes do not influence the evolution of these traits in this population of D. melanogaster. There was no direct response to artificial selection for the ability of first males to deter females from remating. However, we found that the genotype of the first male to mate with a female could influence her time to remate; base stock males were better at deterring females from remating than were males from any of the selection lines. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMedDate not supplied

[Neurodarvinism: models of selection of neuronal groups].

Concept of neurodarvinism is regarded in the context of simulation of the "natural" and "artificial" selection of neurons, synapses and neuronal groups. "Natural" selection of neurons is based on mobile devices built of neuron-like elements. These devices should be capable for adaptation to real surrounding. "Artificial" selection of neurons is performed using computerized "neurointelligence" model operating in a virtual environment. Comparison of the models suggests the advantage of the integration of these approaches.

Artificial Intelligence↗
PubMed2005

Genetic differentiation induced by selection in an inbred population of the silkworm Bombyx mori, revealed by RAPD and ISSR marker systems.

Artificial selection has been widely utilized in breeding programmes concerning the commercially important silk-producing insect Bombyx mori. Selection increases the frequency of homozygotes and makes homozygous effects stronger. Molecular variation induced by selection in the inbred population of B. mori strain Nistari, was assessed in terms of genic differentiation by using a polymorphic profile generated by RAPD and ISSR marker systems. Artificial selection for longer larval duration (LLD) for 4 generations resulted in a significant prolongation of larval duration (F = 89.28; P = 5.14 x 10(-7)). The lines selected for shorter larval duration (SLD) were not significantly different from the control group. RAPD and ISSR primers generated polymorphic profiles when amplified with genomic DNA of individuals of LLD and SLD lines. Distinct markers specific to LLD individuals were observed from the 3rd generation and indicated selection-induced differentiation of allelic variants for longer larval duration. Both SLD and LLD were characterized by high gene diversity (h approximately equal to 0.197) and total heterozygosity (Ht > or =0.26), low homogeneity (chi-square test, p < 0.005) as well as a large coefficient of gene differentiation (Gst > or =0.42) but low gene flow (Nm < or =0.42). Genetic distance was the highest (0.824) between 3rd generations of SLD and LLD. High heterozygosity and prolonged larval duration substituted for shorter larval duration (the traditional trait of fitness) in the Nistari LLD larvae.

Animals↗
PubMed1990

Selection response in traits with maternal inheritance.

Maternal inheritance is the non-Mendelian transmission of traits from mothers to their offspring. Despite its presence in virtually all organisms, acting through a variety of mechanisms, the evolutionary consequences of maternal inheritance are not well understood. Here we review and extend a model of the inheritance and evolution of multiple quantitative characters with complex pathways of maternal effects. Extensions of the earlier model include common family environmental effects not associated with maternal phenotype, sexual dimorphism, and paternal effects (non-Mendelian influence of the father on offspring traits). We find that, in contrast to simple Mendelian inheritance, maternal inheritance produces qualitatively different evolutionary dynamics for two reasons: (1) the response to selection on a set of characters depends not only on their additive genetic variances and covariances, but also on maternal characters that influence them, and (2) time lags in the response to selection create a form of evolutionary momentum. These results have important implications for evolution in natural populations and practical applications in the economic improvement of domesticated species. We derive selection indices that maximize either the economic improvement in a single generation of artificial selection or the asymptotic rate of improvement in long-term selection programmes, based on individual merit or a combination of individual and family merit. Numerical examples show that accounting for maternal inheritance can lead to considerable increases in the efficiency of artificial selection.

Animals↗
PubMed1995

Polygenic mutation in Drosophila melanogaster: the causal relationship of bristle number to fitness.

The association between sternopleural and abdominal bristle number and fitness in Drosophila melanogaster was determined for sublines of an initially highly inbred strain that were maintained by divergent artificial selection for 150 generations or by random mating for 180 generations. Replicate selection lines had more extreme bristle numbers than those that were maintained without artificial selection at the same census size for approximately the same number of generations. The average fitness, estimated by a single generation of competition against a compound autosome strain, was 0.17 for lines selected for high and low abdominal bristle numbers and 0.19 for lines selected for high and low sternopleural bristle number. The average fitness of unselected lines, 0.46, was significantly higher than that of the selection lines. The fitnesses and the relationships of bristle number to fitness in progeny of all possible crosses of high x high (H x H), high x low (H x L) and low x low (L x L) selection lines were examined to determine whether the observed intermediate optima were caused by direct stabilizing selection on bristle number or by apparent stabilizing selection mediated through deleterious pleiotropic fitness effects of mutations affecting bristle number. Although bristle number was nearly additive for progeny of H x H, H x L and L x L crosses among sternopleural bristle selection lines, their mean fitnesses were not significantly different from each other, or from the mean fitness of the unselected lines, suggesting partly or completely recessive pleiotropic fitness effects cause apparent stabilizing selection. The average fitness of the progeny of H x H abdominal bristle selection lines was not significantly different from the fitness of unselected lines, but the mean fitness of the progeny of L x L crosses was not significantly different from that of the pure low lines. This is consistent with direct selection against low but not high abdominal bristle number, but the interpretation is confounded by variation in average degree of dominance for fitness (on average recessive in the high abdominal bristle selection lines and additive in the low abdominal bristle selection lines). Neither direct stabilizing selection nor pleiotropy, therefore, can account for all the observations.

Animals↗
PubMed2005

Selective sweep mapping of genes with large phenotypic effects.

Many domestic dog breeds have originated through fixation of discrete mutations by intense artificial selection. As a result of this process, markers in the proximity of genes influencing breed-defining traits will have reduced variation (a selective sweep) and will show divergence in allele frequency. Consequently, low-resolution genomic scans can potentially be used to identify regions containing genes that have a major influence on breed-defining traits. We model the process of breed formation and show that the probability of two or three adjacent marker loci showing a spurious signal of selection within at least one breed (i.e., Type I error or false-positive rate) is low if highly variable and moderately spaced markers are utilized. We also use simulations with selection to demonstrate that even a moderately spaced set of highly polymorphic markers (e.g., one every 0.8 cM) has high power to detect regions targeted by strong artificial selection in dogs. Further, we show that a gene responsible for black coat color in the Large Munsterlander has a 40-Mb region surrounding the gene that is very low in heterozygosity for microsatellite markers. Similarly, we survey 302 microsatellite markers in the Dachshund and find three linked monomorphic microsatellite markers all within a 10-Mb region on chromosome 3. This region contains the FGFR3 gene, which is responsible for achondroplasia in humans, but not in dogs. Consequently, our results suggest that the causative mutation is a gene or regulatory region closely linked to FGFR3.

Animals↗
PubMed1978

The geometric theory of selection of artificial teeth: is it valid?

The study was done to determine the validity of William's geometric theory of tooth selection. The maxillary central incisors of 31 subjects were radiographed and photographed; casts were made of the maxillas; and the subjects' faces were photographed. Three dentists classified the form of the maxillary central incisors as shown by intraoral photographs, radiographs made by the parallelling technique, and casts, and also classified the form of the face from frontal-view photographs. The data collected were reduced by an electronic computer to determine if a correlation exists. There was no correlation between the form of the face and the form of the maxillary central incisors.

Cephalometry↗
PubMedDate not supplied

Direct and correlated effects of selection on flight after exposure to thermal stress in Drosophila melanogaster.

To demonstrate how insects may adapt to ecologically relevant levels of heat stress, we performed artificial selection on the ability of Drosophila melanogaster to fly after an exposure to a high but non-lethal thermal stress. Both tolerance and intolerance to heat stress arose very quickly, as only a few generations of selection were necessary to cause significant separation between high and low lines for heat tolerance. Estimates of heritability based on the lines artificially selected for increased flight ability ranged from 0.024 to 0.052, while estimates of heritability based on the lines selected for the inability to fly after heat stress varied between 0.035 and 0.091. Reciprocal F1 crosses among these lines revealed strong additive effects of one or more autosomes and a weaker X-chromosome effect. This variation apparently affected flight specifically; neither survival to a more extreme stress nor knockdown by high temperature changed between lines selected for high and low heat tolerance as measured by flight ability. As the well-studied heat-shock response is associated with heat tolerance as measured by survival and knockdown, the aspects of the stress physiology that actually affect flight ability remains unknown.

Animals↗
PubMed2001

Selection for recombination in small populations.

The reasons that sex and recombination are so widespread remain elusive. One popular hypothesis is that sex and recombination promote adaptation to a changing environment. The strongest evidence that increased recombination may evolve because recombination promotes adaptation comes from artificially selected populations. Recombination rates have been found to increase as a correlated response to selection on traits unrelated to recombination in several artificial selection experiments and in a comparison of domesticated and nondomesticated mammals. There are, however, several alternative explanations for the increase in recombination in such populations, including two different evolutionary explanations. The first is that the form of selection is epistatic, generating linkage disequilibria among selected loci, which can indirectly favor modifier alleles that increase recombination. The second is that random genetic drift in selected populations tends to generate disequilibria such that beneficial alleles are often found in different individuals; modifier alleles that increase recombination can bring together such favorable alleles and thus may be found in individuals with greater fitness. In this paper, we compare the evolutionary forces acting on recombination in finite populations subject to strong selection. To our surprise, we found that drift accounted for the majority of selection for increased recombination observed in simulations of small to moderately large populations, suggesting that, unless selected populations are large, epistasis plays a secondary role in the evolution of recombination.

Animals↗
PubMed1994

[Pathological mitoses in clones of the RA-2 subline of rat transplantable rhabdomyosarcoma selected for increased and decreased frequencies of the formation of spontaneous micronuclei].

Cell substrains with increased and decreased spontaneous levels of micronuclei have been obtained by artificial selection. Clones of the substrains were investigated for mitotic division fidelity. About 200 mitoses were investigated in each clone. Frequencies of mitotic abnormalities such as ana- and telophases with bridge, chromosome and fragment delays at ana- and telophases, scattered chromosomes, chromosomes dislocated from spindle at metaphases and tripolar ana- and telophases were significantly higher in substrains with increased level of micronuclei. This finding indicates that reasons for arising of spontaneous micronuclei and alterations in mitotic division fidelity are the same or closely related. These reasons can be amplified as a result of the artificial selection.

Animals↗