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Efficient marker-based recurrent selection for multiple quantitative trait loci.

We studied the efficiency of recurrent selection based solely on marker genotypes (marker-based selection), in order to increase favourable allele frequency at 50 previously detected quantitative trait loci (QTLs). Two selection procedures were investigated, using computer simulations: (1) Truncation Selection (MTS), in which individuals are ranked based on marker score, and best individuals are selected for recombination; and (2) QTL Complementation Selection (QCS), in which individuals are selected such that their QTL composition complements those individuals already selected. Provided QTL locations are accurate, marker-based selection with a population size of 200 was very effective in rapidly increasing frequencies of favourable QTL alleles. QCS methods were more effective than MTS for improving the mean frequency and fixation of favourable QTL alleles. Marker-based selection was not very sensitive to a reduction in population size, and appears valuable to optimize the use of molecular markers in recurrent selection programmes.

Alleles↗

Response to selection for rapid chill-coma recovery in Drosophila melanogaster: physiology and life-history traits.

Resistance to low temperatures can vary markedly among invertebrate species and is directly related to their distribution. Despite the ecological importance of cold resistance this trait has rarely been studied genetically, mainly because low and variable fitness of offspring from cold-stressed mothers makes it difficult to undertake selection experiments and compare cold resistance of parents and offspring. One measure of cold resistance that varies geographically in Drosophila melanogaster and that is amenable to genetic analysis is chill-coma recovery. Three replicate lines of D. melanogaster were selected every second generation, for over 30 generations, for decreased recovery time following exposure to 0 degrees C. Correlated responses were scored to characterize underlying physiological traits and to investigate interactions with other traits. Lines responded rapidly to the intermittent selection regime with realized heritabilities varying from 33% to 46%. Selected lines showed decreased recovery time after exposure to a broad range of low temperatures and also had a lower mortality following a more severe cold shock, indicating that a general mechanism underlying cold resistance had been selected. The selection response was independent of plastic changes in cold resistance because the selected lines maintained their ability to harden (i.e. a short-term exposure to cool temperature resulted in decreased recovery time in subsequent chill-coma assays). Changes in cold resistance were not associated with changes in resistance to high temperature exposure, and selected lines showed no changes in wing size, development time or viability. However, there was a decrease in longevity in the selected lines due to an earlier onset of ageing. These results indicate that chill-coma recovery can be rapidly altered by selection, as long as selection is undertaken every second generation to avoid carry-over effects, and suggest that lower thermal limits can be shifted towards increased cold resistance independently of upper thermal limits and without tradeoffs in many life-history traits.

Acclimatization↗

p53 mutations and tetraploids under r- and K-selection.

Cotransfection of rat embryo fibroblasts with c-myc and activated H-ras oncogenes is one experimental model of the multistep oncogenesis associated with p53 mutations and aneuploidy. Using the model, we found that selection processes, e.g., r- and K-selection, affect emergence of p53 mutants and tetraploids. Culture optimum for logarithmic growth (r-selection) selected p53 mutants as they proliferated rapidly, while in confluent culture (K-selection) tetraploids emerged regardless of the p53 status. Transfection of the mutated p53 gene with dominant negative functions eradicated untransfected cells under both r- and K-selection. However, these p53 mutants can be eradicated under K-selection by cells with normal p53 function and that had been selected under prolonged K-selection. The presence of competitors and the type of selection should determine whether or not p53 mutants and/or tetraploids predominate. These observations strengthen the importance of selection processes in case of cancer.

Animals↗

Butterfly selected lines explore the hormonal basis of interactions between life histories and morphology.

Hormonal mechanisms underlie many life-history traits and their interactions. We studied the role of ecdysteroids with regard to wing pattern and development time of the polyphenic butterfly Bicyclus anynana. Ecdysteroid titers and sensitivity to ecdysone injection were assayed for two-trait selected lines (ventral eyespot size and development time concurrently). These two traits are genetically and phenotypically coupled, having a common endocrinal basis. Two-trait selection had been applied both antagonistically (opposite the correlation) and synergistically (in the same direction as the correlation). Although selected lines had diverged most in eyespot size, the widest differences in timing of ecdysteroid titers were observed between the development time selection regimes; fast selected lines had an earlier hormonal increase after pupation than slow selected lines (even when corrected for differential pupal times). This endocrine peak was also earlier for females than for males. Furthermore, sensitivity to ecdysone injection as measured by a subsequent decrease in pupal time was significantly lower for slow selected lines than for fast or unselected lines. We conclude that the observed response in eyespot size to artificial selection must have been achieved via alteration of, or selection on, other developmental mechanisms, because the dynamics of the alternative, hormonal, pathway were dictated by development time selection. The developmental system is flexible enough to allow evolution in directions opposing the correlation between wing pattern and developmental time, and responses to selection are not constrained by a shared hormonal system.

Animals↗

The evolution of infidelity in socially monogamous passerines: the strength of direct and indirect selection on extrapair copulation behavior in females.

Many studies have been aimed at understanding the maintenance of female infidelity in socially monogamous birds. Because engaging in extrapair copulations (EPCs) is believed to be costly for females, it has been argued that EPC behavior must bring indirect benefits to females by elevating offspring fitness. We use empirical data from the literature to assess the relative strength of indirect and direct selection on female EPC behavior, using quantitative genetic approximations of selection. This analysis confirmed that there is generally negative direct selection on EPC behavior caused by depressed paternal investment by social males. In contrast, there was no significant positive indirect selection on EPC behavior in females. A comparison between the two types of selection suggests that the force of direct negative selection is generally much stronger than that of indirect positive selection. Indirect selection is thus unlikely to maintain EPC behavior in the face of direct selection against it. We suggest that EPCs may instead be the result of antagonistic selection on loci influencing the outcome of male-female encounters and that EPC behavior per se may not be adaptive for females but may reflect sexual conflict due to strong selection in males to achieve extrapair copulations.

Animals↗

The effect of selection on genealogies.

The coalescent process can describe the effects of selection at linked loci only if selection is so strong that genotype frequencies evolve deterministically. Here, we develop methods proposed by Kaplan, Darden, and Hudson to find the effects of weak selection. We show that the overall effect is given by an extension to Price's equation: the change in properties such as moments of coalescence times is equal to the covariance between those properties and the fitness of the sample of genes. The distribution of coalescence times differs substantially between allelic classes, even in the absence of selection. However, the average coalescence time between randomly chosen genes is insensitive to the current allele frequency and is affected significantly by purifying selection only if deleterious mutations are common and selection is strong (i.e., the product of population size and selection coefficient, Ns>3). Balancing selection increases mean coalescence times, but the effect becomes large only when mutation rates between allelic classes are low and when selection is extremely strong. Our analysis supports previous simulations that show that selection has surprisingly little effect on genealogies. Moreover, small fluctuations in allele frequency due to random drift can greatly reduce any such effects. This will make it difficult to detect the action of selection from neutral variation alone.

Biological Evolution↗

Selective neutrality of 6PGD allozymes in E. coli and the effects of genetic background.

We have used gluconate-limited chemostats to study selective differences between isogenic strains of Escherichia coli K12 into which four naturally occurring alleles coding for allozymes of 6-phosphogluconate dehydrogenase (6PGD) had been transferred. The limit of detectability of selection with our procedures is a selection coefficient of 0.5%. In the normal E. coli K12 genetic background, all alleles are selectively neutral or nearly neutral. The absence of detectable selection does, however, depend on genetic background and on such environmental factors as cell density. In a genetic background containing a mutation that cuts off the alternative metabolic route for 6-phosphogluconate, selection between allozymes can be detected, and the selection is in the direction expected from the measured apparent Km values of the allozymes. Even when the alternative metabolic route is not blocked by mutation, one of the 6PGD allozymes has a detrimental, but density-dependent, interaction with a mutation conferring resistance to bacteriophage T5. In all cases, the observed selection is due to the allozymes themselves (or to associated regulatory elements), as the selection disappears when the chemostats are limited by a different carbon source (ribose plus succinate). Nevertheless, the four alleles do seem to be selectively neutral or nearly neutral in the normal E. coli K12 genetic background. Moreover, the distribution of allele frequencies in natural populations of E. coli is in accord with the expectations of selective neutrality.

Alleles↗

Direct and correlated response to divergent selection for serum immunoglobulin M and G levels in chickens.

Two pairs of chicken lines were divergently selected for serum immunoglobulin M and G levels at 10 wk of age to examine the effect of selection on direct and correlated traits. After three generations of selection, the lines were tested for their ability of antibody production against SRBC, a T cell dependent antigen. At 14 and 17 wk of age, the lines were immunized intravenously with 1 mL of 5% SRBC solution. Blood samples were collected at 7 and 14 d of post primary immunization (PPI) and post secondary immunization (PSI). Selection was effective (P < 0.01) in changing the serum immunoglobulin M levels. The G levels were changed in a downward direction initially in the high line. The differences between the high immunoglobulin M (HIM) and low immunoglobulin M (LIM) lines as well as high immunoglobulin G (HIG) and low immunoglobulin G (LIG) lines became larger during the course of selection. Selection differentials varied considerably during the selection, but the selection response was almost constant. Realized heritability was relatively high, ranging from 0.58 to 0.66 and from 0.40 to 0.60 for the IgM and IgG selected lines, respectively. Total antibody titers to SRBC differed significantly (P < 0.01) between the HIM and LIM lines at 7 and 14 d PPI, and 7 d PSI. The HIM line also produced significantly higher mercaptoethanol resistant antibody titers to SRBC than the LIM line at 7 and 14 d PPI and PSI. The LIG line had significantly higher total antibody titers to SRBC than the HIG line at both 7 and 14 d of PPI and PSI. From these results, it is suggested that selection of chickens on the basis of serum immunoglobulin isotypes may change antibody producing cells as well as other immunocompetent cells that modulate the immune response of the selected lines.

Animals↗

Genetic relationship among lines and smooth muscle and ovarian follicular development within lines of Japanese quail in two long-term selection studies.

Smooth muscle tumor and ovarian follicular development were studied in lines of Japanese quail selected for increased 4-wk BW (HW, P, and T) and their randombred controls (C and R1). The lines studied were from long-term selection studies at The Ohio State University (HW and R1) and The University of Georgia (P, T, and C). To study the genetic relationship among the lines in the two selection studies, the C, P, HW, and R1 lines were DNA-fingerprinted by digestion of the DNA with the HaeIII restriction enzyme and using Jeffreys' 33.6 probe. The BW of females at 4 wk of age and at the end of a 240-d egg production period were similar for the C and R1 lines. The BW of the selected lines was ranked P > T > HW for both measurements. Smooth muscle tumors were found in the oviducal ligaments adjacent to the magnum. A greater percentage of hens from the BW-selected lines had smooth muscle tumors of greater weight than the randombred control lines, which did not differ in tumor incidence or weight. The P and T lines had a greater incidence of multiple-lobed tumors than the HW line. Based on bandsharing (BS) of DNA fingerprints, the Georgia and Ohio lines did not appear to be closely related, suggesting that, perhaps, the smooth muscle tumors in the BW-selected lines in the two studies might have resulted from pleiotrophic effects of genes affecting growth or to genes closely linked to the growth genes. The BW-selected lines in both selection studies had more ovarian follicles in rapid development, which were of greater weight, than the randombred control lines. The HW line had a larger number of ovarian follicles in rapid development than the P and T lines. The percentage of hens with atretic follicles was greater in the BW-selected lines. The results of the present study suggest that the effect of BW selection on ovarian follicular development may occur early in selection (within the first 30 generations) and is not influenced by additional genetic changes in BW.

Animal Husbandry↗

Genetic constraints on floral evolution in a sexually dimorphic plant revealed by artificial selection.

Sexual dimorphism is one of the most widespread and recognizable patterns of phenotypic variation in the biotic world. Sexual dimorphism in floral display is striking in the dioecious plant Silene latifolia, with males making many, small flowers compared to females. We investigated this dimorphism via artificial selection on two populations to determine whether genetic variation exists within populations for flower size and the extent of the between-sex correlation, whether a flower size and number trade-off exists within each sex, and whether pollen and ovule production vary with flower size. We selected for decreased flower size (calyx width) in females and increased flower size in males and measured the response to selection in size and correlated responses in flower dry mass, flower number, and pollen or ovule number per flower. Four bouts of selection in each of two selection programs were performed, for a total of three selection lines to decrease size, three to increase it, and two control lines. Flower size always significantly responded to selection and we always found a significant correlated response in the sex not under selection. Selection decreased but did not eliminate the sexual dimorphism in flower dry mass and number. A negative relationship between flower size and number within each sex was revealed. Whereas ovule number showed a significant correlated response to selection on flower size, pollen number did not. Our results indicate that although substantial additive genetic variation for flower size exists, the high between-sex genetic correlation would likely constrain flower size from becoming more sexually dimorphic. Furthermore, floral display within each sex is constrained by a flower size and number trade-off. Given this trade-off and lack of variation in pollen production with flower size, we suggest that sexual dimorphism evolved via sexual selection to increase flower number in males but not females.

Biological Evolution↗

Evolutionary potential of Chamaecrista fasciculata in relation to climate change. I. Clinal patterns of selection along an environmental gradient in the great plains.

Climate change will alter natural selection on native plant populations. Little information is available to predict how selection will change in the future and how populations will respond. Insight can be obtained by comparing selection regimes in current environments to selection regimes in environments similar to those predicted for the future. To mimic predicted temporal change in climate, three natural populations of the annual legume Chamaecrista fasciculata were sampled from a climate gradient in the Great Plains and progeny of formal crosses were reciprocally planted back into common gardens across this climate gradient. In each garden, native populations produced significantly more seed than the other populations, providing strong evidence of local adaptation. Phenotypic selection analysis conducted by site showed that plants with slower reproductive development, more leaves, and thicker leaves were favored in the most southern garden. Evidence of clinal variation in selection regimes was also found; selection coefficients were ordered according to the latitude of the common gardens. The adaptive value of native traits was indicated by selection toward the mean of local populations. Repeated clinal patterns in linear and nonlinear selection coefficients among populations and within and between sites were found. To the extent that temporal change in climate into the future will parallel the differences in selection across this spatial gradient, this study suggests that selection regimes will be displaced northward and different trait values will be favored in natural populations.

Adaptation, Physiological↗

Expression of the heat-shock protein HSP70 in Drosophila buzzatii lines selected for thermal resistance.

The level of HSP70 expression induced by a non-lethal high temperature was examined in lines selected for increased thermal resistance and in corresponding control lines of Drosophila buzzatii, in order to test if selection for high temperature resistance leads to an increased level of HSP70 expression. The lines used were selected for up to 64 generations either as adults or through all larval stages. In adult selection lines, hard selection was implemented every second generation after mild heat hardening. In larval selection lines, larvae were exposed each generation to laboratory "natural" selection. Generally lines selected as adults showed a higher HSP70 expression than did controls, both in third instar larvae and in adults. A strong negative response to selection of HSP70 expression was found in all lines that were selected at cycling temperatures during larval development. The results suggests that a trade off between heat resistance in form of HSP70 expression and fecundity/fertility are responsible for the level of HSP70 expression. The effect of the different methods of selection on HSP70 expression suggests that heat resistance constitutes more than one trait.

Animals↗

Selection responses for the number of fertile eggs of the Brown Tsaiya duck (Anas platyrhynchos) after a single artificial insemination with pooled Muscovy (Cairina moschata) semen.

A seven-generation selection experiment comprising a selected (S) and a control (C) line was conducted with the objective of increasing the number of fertile eggs (F) of the Brown Tsaiya duck after a single artificial insemination (AI) with pooled Muscovy semen. Both lines consisted of about 20 males and 60 females since parents in each generation and each female duck was tested 3 times, at 26, 29 and 32 weeks of age. The fertile eggs were measured by candling at day 7 of incubation. The selection criterion in the S line was the BLUP animal model value for F. On average, 24.7% of the females and 15% of the males were selected. The direct responses to the selection for F, and correlated responses for the number of eggs set (Ie), the number of total dead embryos (M), the maximum duration of fertility (Dm) and the number of hatched mule ducklings (H) were measured by studying the differences across the generations of selection between the phenotypic value averages in the S and C lines. The predicted genetic responses were calculated by studying the differences between the S and C lines in averaged values of five traits of the BLUP animal model. The selection responses and the predicted responses showed similar trends. There was no genetic change for Ie. After seven generations of selection, the average selection responses per generation were 0.40, 0.33, 0.42, 0.41 genetic standard deviation units for F, M, Dm, and H respectively. Embryo viability was not impaired by this selection. For days 2-8 after AI, the fertility rates (F/Ie) were 89.2% and 63.8%, the hatchability rates (H/F) were 72.5% and 70.6%, and (H/Ie) were 64.7% and 45.1% in the S and C lines respectively. It was concluded that upward selection on the number of fertile eggs after a single AI with pooled Muscovy semen may be effective in ducks to increase the duration of the fertile period and the fertility and hatchability rates with AI once a week instead of twice a week.

Animals↗

Sexual selection, germline mutation rate and sperm competition.

BACKGROUND: An important component of sexual selection arises because females obtain viability benefits for their offspring from their mate choice. Females choosing extra-pair fertilization generally favor males with exaggerated secondary sexual characters, and extra-pair paternity increases the variance in male reproductive success. Furthermore, females are assumed to benefit from 'good genes' from extra-pair sires. How additive genetic variance in such viability genes is maintained despite strong directional selection remains an evolutionary enigma. We propose that sexual selection is associated with elevated mutation rates, changing the balance between mutation and selection, thereby increasing variance in fitness and hence the benefits to be obtained from good genes sexual selection. Two hypotheses may account for such elevated mutation: (1) Increased sperm production associated with sperm competition may increase mutation rate. (2) Mutator alleles increase mutation rates that are revealed by the expression of condition-dependent secondary sexual characters used by choosy females during their mate choice. M Petrie has independently developed the idea that mutator alleles may account for the maintenance of genetic variation in viability despite strong directional selection. RESULTS: A comparative study of birds revealed a positive correlation between mutation rate at minisatellite loci and extra-pair paternity, but not between mutation rate and relative testes mass which is a measure of relative sperm production. Minisatellite mutation rates were not related to longevity, suggesting a meiotic rather than a mitotic origin of mutations. CONCLUSION: We found evidence of increased mutation rate in species with more intense sexual selection. Increased mutation was not associated with increased sperm production, and we suggest that species with intense sexual selection may maintain elevated mutation rates because sexual selection continuously benefits viability alleles expressed in condition-dependent characters. Sexual selection may increase mutational input, which in turn feeds back on sexual selection because of increased variance in viability traits.

Animals↗

Positive selection.

The use of a new mode of selection-positive selection-has been demonstrated to be successful in a large variety of monocot and dicot species. This selection differs from more traditional modes of selection in which compounds such as antibiotics or herbicides are used to kill nontransformed cells (negative selection). In the case of positive selection, a transformed cell acquires the ability to metabolize a substrate that it previously could not use (or not use efficiently) and thereby grows out of the mass of nontransformed tissue. Positive selection can be of many types from inactive forms of plant growth regulators that are then converted to active forms by the transferred enzyme to alternative carbohydrate sources that are not utilized efficiently by the nontransformed cells that become available upon transformation with an enzyme that allows them to be metabolized. Nontransformed cells either grow slowly in comparison to transformed cells or not at all. Using positive selection, nontransformed cells may die, but, typically, production of phenolic compounds observed with negative selection markers does not occur. In many cases, this effect contributes to higher transformation efficiencies, as these compounds can negatively influence the growth of transformed cells. The use of one form of positive selection-transformation with phosphomannose isomerase followed by selection on mannose containing media-is presented here as an example.

Indicators and Reagents↗

The structured ancestral selection graph and the many-demes limit.

We show that the unstructured ancestral selection graph applies to part of the history of a sample from a population structured by restricted migration among subpopulations, or demes. The result holds in the limit as the number of demes tends to infinity with proportionately weak selection, and we have also made the assumptions of island-type migration and that demes are equivalent in size. After an instantaneous sample-size adjustment, this structured ancestral selection graph converges to an unstructured ancestral selection graph with a mutation parameter that depends inversely on the migration rate. In contrast, the selection parameter for the population is independent of the migration rate and is identical to the selection parameter in an unstructured population. We show analytically that estimators of the migration rate, based on pairwise sequence differences, derived under the assumption of neutrality should perform equally well in the presence of weak selection. We also modify an algorithm for simulating genealogies conditional on the frequencies of two selected alleles in a sample. This permits efficient simulation of stronger selection than was previously possible. Using this new algorithm, we simulate gene genealogies under the many-demes ancestral selection graph and identify some situations in which migration has a strong effect on the time to the most recent common ancestor of the sample. We find that a similar effect also increases the sensitivity of the genealogy to selection.

Algorithms↗

Selection theory for marker-assisted backcrossing.

Marker-assisted backcrossing is routinely applied in breeding programs for gene introgression. While selection theory is the most important tool for the design of breeding programs for improvement of quantitative characters, no general selection theory is available for marker-assisted backcrossing. In this treatise, we develop a theory for marker-assisted selection for the proportion of the genome originating from the recurrent parent in a backcross program, carried out after preselection for the target gene(s). Our objectives were to (i) predict response to selection and (ii) give criteria for selecting the most promising backcross individuals for further backcrossing or selfing. Prediction of response to selection is based on the marker linkage map and the marker genotype of the parent(s) of the backcross population. In comparison to standard normal distribution selection theory, the main advantage of our approach is that it considers the reduction of the variance in the donor genome proportion due to selection. The developed selection criteria take into account the marker genotype of the candidates and consider whether these will be used for selfing or backcrossing. Prediction of response to selection is illustrated for model genomes of maize and sugar beet. Selection of promising individuals is illustrated with experimental data from sugar beet. The presented approach can assist geneticists and breeders in the efficient design of gene introgression programs.

Alleles↗

Two-stage selection strategies utilizing marker-quantitative trait locus information and individual performance.

Short- and long-term response to marker-assisted selection in two stages was studied using a stochastic simulation of a closed nucleus herd for beef production. First-stage selection was carried out within families based on information at a fully additive quantitative trait locus (QTL). Second-stage selection strategies were based on 1) individual phenotype, 2) individual phenotype precorrected for QTL, 3) a selection index incorporating phenotype and QTL information, 4) a standard animal model BLUP, and 5) a selection index incorporating marker-QTL information and standard animal model BLUP on records precorrected for QTL. All strategies were efficient in moving the favorable allele at the QTL to fixation, but they differed in the time to reach fixation. Mass selection was less efficient in changing allele frequencies than BLUP. Discounted accumulated response, accounting for the time response was realized and inflation rate, was proposed to rank strategies and to elude the conflict between short- and long-term response in marker-assisted selection. Discounted accumulated response at a time horizon of 20 yr for alternative two-stage selection strategies was compared with conventional BLUP carried out in second stage only. Within-family selection increased discounted accumulated response by more than 11% using Strategy 4 and by up to 12% using Strategy 5 at an inflation rate of 2%. The percentage increase in response was less for highly heritable traits and when the proportion of additive variance explained by the QTL was small. Strategy 5 gave larger response with reduced inbreeding. This strategy also resulted in the lowest cost-benefit ratio, requiring less genotyping per unit of response. Cost-benefit ratio for discounted genotyping and for discounted in vitro production of embryos for traits with low heritability was two to four times that for traits with high heritability. The use of first-stage selection slightly increased the level of inbreeding for both mass (Strategy 1) and BLUP selection (Strategies 4 and 5).

Animals↗