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Rodent malaria-resistant strains of the mosquito, Anopheles gambiae, have slower population growth than -susceptible strains
Maarten J Voordouw1,
Bradley R Anholt1,
Pam J Taylor2 &
Hilary Hurd2
Trade-offs between anti-parasite defence mechanisms and other life history traits limit the evolution of host resistance to parasites and have important implications for understanding diseases such as malaria. Mosquitoes have not evolved complete resistance to malaria parasites and one hypothesis is that anti-malaria defence mechanisms are costly.
We used matrix population models to compare the population growth rates among lines of Anopheles gambiae that had been selected for resistance or high susceptibility to the rodent malaria parasite, Plasmodium yoelii nigeriensis. The population growth rate of the resistant line was significantly lower than that of the highly susceptible and the unselected control lines, regardless of whether mosquitoes were infected with Plasmodium or not. The lower population growth of malaria-resistant mosquitoes was caused by reduced post blood-feeding survival of females and poor egg hatching.
With respect to eradicating malaria, the strategy of releasing Plasmodium-resistant Anopheles mosquitoes is unlikely to be successful if the costs of Plasmodium-resistance in the field are as great as the ones measured in this study. High densities of malaria-resistant mosquitoes would have to be maintained by continuous release from captive breeding facilities.
Parasites exert strong selection on their hosts to evolve resistance mechanisms that avoid or reduce the negative fitness consequences of infection. Host resistance includes any mechanism (behaviour, morphology, physiological or immune response) that results in the avoidance, clearance, or tolerance of parasitic infections [1]. Theory predicts that the evolution of these resistance mechanisms in the host is constrained by antagonistic pleiotropy, when one allele affects two or more traits with opposite effects on fitness [2, 3]. Such costs of evolving resistance have been demonstrated by measuring negative genetic correlations (genetic trade-offs) between immunity and other life history traits in selection or quantitative genetic experiments [4–9].
Most of these studies measure several life history traits and report that some of these fitness components are negatively correlated with host resistance whereas others are not [6, 7]. Almost none of these studies have tried to combine multiple fitness components into a single measure of lifetime fitness. This is important because the evolution of immunity, like any other trait, ultimately depends on its correlation with lifetime fitness [10].
In organisms with age or stage-structured life histories, one widely recognized measure of lifetime fitness is the geometric population growth rate, λ [11]. To estimate λ one uses matrix algebra to model the life cycle of the organism [12]. The parameter λ depends on the age-specific or stage-specific vital rates, which are difficult to measure for a single individual. Hence, this approach works best when comparing groups of individuals (e.g., parasite-resistant versus parasite-susceptible host genotypes). One advantage of combining multiple life history traits into a single measure of lifetime fitness such as λ is that it avoids the problem of multiple comparisons and type I error. Another advantage is that all life history traits can be expressed in units of λ. This allows us to use parameter estimates (i.e., biological significance) rather than p-values (statistical significance) to determine which life history traits caused the difference in lifetime fitness. The purpose of the present study is to demonstrate the utility of this approach using a previously published data set by Hurd et al. [13] on the fitness costs and benefits of malaria resistance in Anopheles gambiae mosquitoes. A. gambiae is the most important vector of human malaria in Africa and is the main target of attempts to engineer a malaria-resistant mosquito [14]. We review the host-parasite interactions between the mosquito host and the malaria parasite and the study of Hurd et al. [13] below.
Malaria parasites (genus Plasmodium) are transmitted between vertebrate hosts during blood feeding by female Anopheles mosquitoes. Following an infected blood meal the sexual stages of Plasmodium release gametes into the mosquito mid-gut and fertilization occurs. The zygotes develop into ookinetes that cross the epithelial layer of the mosquito mid-gut within 24 hours of fertilization. The ookinetes transform into oocysts that grow for one to two weeks on the exterior of the mid-gut before releasing thousands of sporozoites into the mosquito hemocoel. The sporozoites migrate to the mosquito salivary glands where they are transmitted to the next vertebrate host during blood feeding.
From the perspective of the female mosquito, Plasmodium is a parasite because it reduces both reproductive success [15–17] and survival [18]. Mosquitoes have evolved a number of defence mechanisms to protect themselves from Plasmodium [19–22]. Natural populations of mosquitoes have considerable genetic variation in Plasmodium resistance [23]. Several reviews have speculated that this variation is maintained by genetic trade-offs between Plasmodium resistance and other life history traits [24, 25]. Hurd et al. [13] tested this hypothesis in A. gambiae by comparing eight different life history traits between strains that they had selected for resistance or high susceptibility to the rodent malaria parasite, P. yoelii nigeriensis. They found no significant differences in the two life history traits they deemed most important, longevity and fertility and concluded there was no difference in fitness between the refractory and the highly susceptible genotypes.
We re-analyzed the data of Hurd et al. [13] using stage-classified matrix population models [12] to combine all of the life history traits into an estimate of λ. We found that the malaria-resistant A. gambiae mosquitoes have a lower population growth rate than malaria-susceptible mosquitoes (regardless of whether mosquitoes were infected with Plasmodium). Our estimates of λ suggest that the population size of the malaria-resistant line will be half that of the susceptible line in just 23 days. This is the first study to show that there are high fitness costs for mosquitoes to evolve resistance to malaria, which has important implications for strategies that seek to reduce malaria transmission by releasing malaria-resistant mosquitoes.
Differences in λ between malaria-refractory and -susceptible genotypes
We used matrix population models to estimate the geometric population growth rate (λ) for genotypes of A. gambiae that were resistant or highly susceptible to the rodent malaria parasite P. yoelii nigeriensis, as well as an unselected control genotype (see Methods). The mean λ (± standard error) of the refractory genotype (1.062 ± 0.0113) was lower than that of the highly susceptible (1.097 ± 0.0092) and the unselected control genotype (1.100 ± 0.0135). For explaining the most variation in λ with the fewest possible parameters, the best model according to our model selection criteria (low AIC score, parsimony) included the main effects of group, environment, genotype and the group:environment interaction (model 5 in Table 1). In this model, genotype (F2,16 = 5.675, p = 0.014) and the group:environment interaction (F4,16 = 3.506, p = 0.031) were statistically significant and accounted for 21.7% and 26.8% of the variation in λ, respectively (Table 2). For model 5, the first planned comparison found that the difference between the mean λ of the unselected control genotype and that of the selected genotypes (i.e., the refractory and highly susceptible genotypes combined) was not significant (p = 0.073). This indicates that the selection regime did not affect λ (e.g. via inbreeding). The second planned comparison found that the mean λ of the refractory genotype was significantly lower than that of the highly susceptible genotype (p = 0.014). This indicates that the evolution of Plasmodium resistance in the refractory genotype reduced λ. The population doubling times of the refractory, the highly susceptible, and the unselected control genotypes are 11.5 days, 7.5 days, and 7.3 days, respectively. This means that after 23 days, a population of refractory genotypes will be half the size of a population of highly susceptible or unselected control genotypes (2 doublings versus 3).
Table 1 Linear models of the population growth rate (λ).
Table 2 Significance testing of the terms in the best model.
The significant group:environment interaction (Table 2) suggests that the effect of group is contingent on the environment (and vice versa). For example, for the three environments – uninfected blood, infected blood, infected blood and stressed – females from the red group have the highest, intermediate, and lowest population growth (averaged across genotypes), respectively (Figure 1). Alternatively, because each of the 9 combinations of group and environment were fed on a different mouse, random variation among mice may be causing the group:environment interaction. Our best model (model 5 in Table 1) is therefore identical to one that would fit genotype and mouse as fixed factors with no genotype:mouse interaction.
The population growth rates of the 3 genotypes in 3 different environments. The population growth rate (λ = Lambda) is shown as a function of group (black, red, green), environment (uninfected blood meal, infected blood meal, infected blood meal and subsequently stressed), and genotype (unselected control, refractory, highly susceptible). The groups are shown with different symbols and line types (black = solid circles and solid line; red = open circles and dashed line; green = open triangles and dotted line), the environments are shown in different panels, and the genotypes are shown on the x-axis. Each of the lines that connect three points in Figure 2 represents a different mouse.
Differences in the life cycle parameters between genotypes
The refractory genotype was outperformed by the highly susceptible genotype on all the life cycle parameters except pupation success (Table 3). The refractory genotype was also outperformed by the unselected control genotype on all the life cycle parameters except egg production (Table 3). The unselected control genotype had higher pupation and egg laying success than the highly susceptible genotype (Table 3). After correcting for multiple comparisons, α = 0.05/21 = 0.002, none of differences in Table 3 are statistically significant.
Table 3 Differences in the life cycle parameters among genotypes.
From the pair wise differences in Table 3 it is difficult to determine which life cycle parameters are driving the differences in λ because they are in different units. To determine which life cycle parameters contribute to differences in λ between pairs of genotypes we must use the matrix entries instead (see Table 4 and the methods on how the matrix entries are related to the life cycle parameters). In Figure 2, the pair wise differences in the matrix entries are all in the same units of λ after scaling them by the sensitivities (of the average stage-classified matrix). In Figure 2 the emphasis is on the direction and magnitude of the difference in the scaled matrix entry between pairs of genotypes rather than statistical significance (again, none of the 95% confidence intervals in Figure 2 are statistically significant after correcting for multiple comparisons). The lower λ of the refractory genotype was primarily driven by lower egg hatching success (p21) and the lower transition of mated to gravid females (p65). The transition p65 includes both the proportion of females that took a blood meal (p.blood) and the proportion of females that survived blood digestion (p.surv.blood; see Table 4). As we were primarily interested in the latter, we set p.blood equal to one, and recalculated λ and the stage-classified matrices for the 27 combinations. The results were the same indicating that reduced post blood-feeding survival caused the fitness cost of the refractory genotype.
Table 4 The ten parameters of the laboratory life cycle of A. gambiae.
The life cycle parameters that cause the differences in λ among the 3 genotypes. The pair wise differences in the matrix entries between the three pairs of genotypes: (a) unselected control – highly susceptible, (b) unselected control – refractory, and (c) highly susceptible – refractory. The subscripts (i, j) of the matrix entry (pij) refer to the six stages: (1) egg, (2) larvae, (3) pupae, (4) virgin, (5) mated, and (6) gravid females. The differences in the matrix entries are scaled by the sensitivities of the average stage-classified matrix to show how they contribute to differences in λ between each pair of genotypes. For each matrix entry, the mean difference between the two genotypes and the 95% confidence interval are shown for the 9 combinations of group and environment. None of the differences are statistically significant after correcting for multiple comparisons.
Sensitivity and elasticity analyses of λ
In the previous paragraph, we used the sensitivities to scale the differences in matrix entries between pairs of genotypes to determine which life cycle parameters caused the differences in λ between genotypes. The sensitivity and elasticity analyses also indicate which life cycle parameters have the greatest influence on λ. Such knowledge is valuable for understanding life history evolution in A. gambiae and for any strategy seeking to control mosquito population growth.
The sensitivity of λ to the matrix entry pij is ∂λ/∂pij, the derivative of λ with respect to pij. The sensitivities are analogous to the partial regression coefficients of a multiple regression where all the variables are measured in different units (e.g. survival, fertility, probability of blood feeding). For the average stage-classified matrix, the sensitivity of λ to the transition from larva to pupa was the highest (p32 = 0.74), followed by sensitivity of λ to larval survival (p22 = 0.29), gravid female survival (p66 = 0.28), the transition from mated to gravid female (p65 = 0.25), and the transition from egg to larva (p21 = 0.20; Figure 3).
The contribution of the life cycle parameters to the population growth rate of A. gambiae. The sensitivity (a) and the elasticity (b) of λ to the stage-classified matrix entries of A. gambiae. For each matrix entry (pij), the subscripts i and j refer to the six stages: (1) egg, (2) larvae, (3) pupae, (4) virgin females, (5) mated females, and (6) gravid females. For example, p11 is the daily probability that an egg will survive whereas p21 is the daily probability that an egg will hatch and become a larva. For each matrix entry, the mean and standard error are shown for the 27 combinations of group, environment, and genotype.
The elasticity of λ to the matrix entry pij is (pij/λ)*(∂λ/∂pij) and can be interpreted as the proportional contribution of pij to λ. The elasticities are analogous to the partial regression coefficients of a multiple regression where all the variables have been standardized to z-scores (mean 0, standard deviation 1). The elasticity of λ to larval survival was the highest (p22 = 0.24), followed by gravid female survival (p66 = 0.20; Figure 3). Hence both the sensitivity and the elasticity analysis suggest that larval survival to the pupa stage (p22 and p32) and gravid female survival (p66) have the greatest influence on the lifetime fitness of female A. gambiae mosquitoes.
This study shows the utility of using matrix population models to combine multiple life history traits into a single estimate of the population growth rate (λ) when testing for genetic trade-offs between parasite resistance and lifetime fitness. The most important result of this study is that our estimates of λ suggest that a population of refractory mosquitoes will be half the size of a population of highly susceptible mosquitoes in just 23 days. Hence, complete resistance to Plasmodium can be costly for A. gambiae and may explain why natural populations of mosquitoes maintain genetic variation for malaria resistance. The strategy to combat malaria by replacing natural mosquito populations with transgenic, malaria-resistant mosquitoes will fail if the transgenics carry similar fitness costs.
The population growth rate of the refractory genotype was always lower than that of the highly susceptible genotype (Figure 1). This suggests that the immune mechanisms required for complete refractoriness to P. yoelii nigeriensis are costly for A. gambiae and would not evolve under the laboratory conditions used in this study. This conclusion is supported by Hurd et al.'s [13] laboratory evolution experiment where mosquitoes fed exclusively on infected mice over 22 generations did not evolve refractoriness. Likewise, two recent population genetic studies estimated the strength of selection on 8 different anti-Plasmodium defence genes in the A. gambiae species complex and concluded that there was no evidence for strong directional or balancing selection on these genes [26, 27]. Such non-significant patterns of selection are expected if the costs of evolving Plasmodium-resistance genes are similar to the costs of Plasmodium infection. More generally, our results are consistent with numerous studies on other host-parasite systems that have found that the evolution of anti-parasite defence mechanisms in the host comes at the expense of other life history traits [4, 6, 7].
The conclusions of this study differ from Hurd et al. [13] because we combined all the life cycle parameters into a single measure of fitness, λ. Numerous authors have pointed out the importance of combining the components of fitness (survival, reproduction, development rates) into a measure of lifetime fitness such as λ [11, 12, 28]. Univariate analyses of multiple fitness components do not provide insight into lifetime fitness because they do not account for the conditional dependence of later expressed components of fitness (e.g. fertility) on those expressed earlier (e.g. survival to reproduce). Furthermore, such analyses are likely to give conflicting results because negative correlations between fitness components are common [10, 29]. The ambiguity of this approach is illustrated by the analysis of Hurd et al. [13], which found no clear pattern of differences in fitness components among the three genotypes. Similarly, none of the pair wise t-tests of the 7 life cycle parameters were statistically significant after correcting for multiple comparisons (Table 3). However, after combining the life cycle parameters into a single measure of fitness (λ) we found significant differences among the three genotypes. This study shows that lifetime fitness is the product of many parts and that small, statistically insignificant but consistent differences in these parts can add up to large differences over the course of a life cycle.
Our results are consistent with the only other study to test for genetic trade-offs between malaria resistance and other life history traits in a mosquito [30]. Yan et al. [30] found that their refractory strain of Aedes aegypti was smaller, had lower survivorship and laid fewer eggs than the highly susceptible strain in both the presence and absence of the avian malaria parasite, P. gallinaceum. In contrast to Yan et al. [30], the major strengths of this study were that we (1) selected the refractory and highly susceptible strains from the same population, (2) included unselected control genotypes allowing us to rule out inbreeding effects, and (3) repeated the experiment three times (i.e. the black, red and green groups). One limitation of this study is that there was no replication of mice within the 9 combinations of group and environment. It is therefore possible that the significant group:environment interaction on λ (model 5 in Table 1) was caused by random variation among mice. It is well known, for example, that the gametocyte density in the vertebrate host influences the infectivity of the blood meal and the subsequent oocyst load in the mosquito [31]. Fortunately, because the three genotypes were blocked by the factor 'mouse', the limitations of the experimental design do not affect the conclusion that the population growth rate of the refractory genotype is lower than that of the other two genotypes.
The life cycle parameters that reduced λ the most for the refractory genotype were post blood-feeding survival and hatching success (Figure 2). The lower post blood-feeding survival suggests that the refractory mosquitoes evolved immune responses that harm both "self" and "non-self" (i.e. autoimmunity costs; [2]). For example, following an infected blood meal, Anopheles females upregulate expression of nitric oxide synthase producing levels of nitric oxide [32] that limit ookinete development [33] but may also be toxic for the mosquito [34]. Similarly, the phenoloxidase cascade responsible for the melanization of oocysts in the midgut produces phenol by-products that may be cytotoxic for the mosquito [35, 36]. The induction of the melanization response in gravid A. gambiae females also reduces the deposition of protein (e.g. vitellin) in the eggs [37]. Studies with Plasmodium-infected Anopheles females have shown reduced vitellin provisioning of eggs, which may result in lower hatch rates [38, 39]. Hence, a trade-off between vitellin egg provisioning and an upregulated immune system post-blood feeding in refractory females is one explanation for their lower egg hatch rates.
We found no evidence that Plasmodium infection reduced the population growth rate of A. gambiae. The main effect of environment (presence versus absence of Plasmodium) was not statistically significant and explained only 8.2% of the variation in λ (Table 2). In contrast, the main effect of genotype accounted for 21.7% of the variation in λ (Table 2). Although it has been repeatedly shown that Plasmodium reduces egg production in Anopheles mosquitoes [15–17] including the Keele population from which the refractory and highly susceptible genotypes were selected by Hurd et al. [13], our sensitivity and elasticity analyses (Figure 3) show that λ is minimally affected by changes in fertility. The effect of Plasmodium on mosquito survival is more controversial [18]. Environmental factors can also influence the virulence of the mosquito-Plasmodium interaction. For example, Lambrechts et al. [40] showed that A. stephensi infected with P. yoelii yoelii suffer more than uninfected individuals when fed on low glucose levels. Other studies have shown that Plasmodium-induced mortality is influenced by humidity, temperature, diet, larval density, and bacterial infection (reviewed in [18]). How this environmental variation structures the virulence of the mosquito-Plasmodium interaction in the field is an open question. In this study, the stressed environment was supposed to mimic field conditions and included cold temperatures, reduced sugar, and cage shaking to induce flight. However, because the experiment did not include an uninfected and stressed treatment it was not possible to determine whether environmental stress increased or decreased the cost of infection.
In this laboratory population of A. gambiae, the population growth rate of the malaria-resistant mosquito genotype was significantly lower than that of the highly susceptible and unselected control genotypes regardless of whether the mosquitoes were fed on Plasmodium-infected or uninfected blood. This cost of refractoriness was driven by lower post-blood feeding survival and egg hatching of refractory females. If the costs of Plasmodium refractoriness in the field are higher than the costs of Plasmodium infection, this may explain why natural populations of A. gambiae are not uniformly resistant to malaria parasites [23]. With respect to the transgenic strategy for eradicating malaria, this study has several important implications. Our sensitivity and elasticity analyses show that the insertion of any anti-Plasmodium defence genes into transgenic mosquitoes must avoid reducing larval survival to the pupa stage at all costs as this life history trait has the greatest influence on λ. Anti-Plasmodium genes (e.g. nitric oxide synthase, or enzymes in the phenoloxidase cascade) that increase the production of toxins (e.g. nitric oxide, phenol by-products) and incur autoimmunity costs may do more harm than good [2]. Fortunately, there is at least one example of a transgenic strain of A. stephensi, which expresses the SM1 peptide in the midgut, that is resistant to the rodent malaria parasite P. berghei, that has a selective advantage over non-transgenic mosquitoes when fed on P. berghei-infected mice, and that does not appear to have a selective disadvantage when fed on uninfected mice [41]. If similar transgenic mosquito strains can be created for human Plasmodium parasites there is room for optimism that the transgenic strategy may yet succeed. However, if transgenic mosquitoes carry similar costs of being refractory to those measured in the present study they would be unable to replace natural populations [14, 42, 43].
Experimental design of the study by Hurd et al. (2005)
Hurd et al. [13] created three replicate selection experiments, referred to as the black, red and green groups. All three groups were sampled from the outbred Keele population, which was created by the balanced interbreeding of four laboratory strains of A. gambiae sensu stricto: the KIL, G3, Zan U and Ifakara strains (see [13]). For each group, there were three selection lines: (1) selection for zero malaria oocysts in the mid gut of female mosquitoes 7 days after an infected blood meal to create the refractory line, (2) selection for high numbers of oocysts in the mosquito mid gut after an infected blood meal to create the susceptible line, and (3) random selection after an uninfected blood meal to create an unselected control line. After 10 generations of selection, the mean oocyst load of the refractory lines (12.1 oocysts per mosquito) was much lower than that of the highly susceptible and control lines (99.2 and 84.4 oocysts per mosquito, respectively). Hurd et al. [13] compared the fitness of the unselected control lines with the outbred Keele population to confirm that no inbreeding depression had occurred.
For each of the 3 groups (black, red, green), Hurd et al. [13] fed the 3 genotypes (unselected control, refractory, highly susceptible) on one uninfected mouse and one P. y. nigeriensis-infected mouse. The uninfected and malaria-infected mice represent the two different blood-feeding environments where the Plasmodium parasite was either absent or present. For each of the 3 groups, a third environment was created where the 3 genotypes were stressed (see [13]) after feeding on one infected mouse. A different mouse was used for each of the 9 combinations of group and environment so that a total of 9 mice were used in the experiment (3 uninfected and 6 infected). For each of the 9 combinations of group and environment, the 3 genotypes were fed on the same mouse.
For each of the 27 combinations of group, environment, and genotype, Hurd et al. [13] measured a number of life history traits starting with ~100 blood fed A. gambiae female mosquitoes including: (1) the proportion of female mosquitoes that took a blood meal, (2) the proportion of females that died while digesting the blood meal (3) the proportion of female mosquitoes that died during oviposition, (4) the number of eggs produced per female, (5) the proportion of eggs that were laid, (6) the proportion of eggs that hatched, and (7) the proportion of larvae that reached the pupae stage.
Stage-classified life cycle of A. gambiae
We classified the life cycle of A. gambiae into six stages: (1) eggs, (2) larvae, (3) pupae, (4) virgin, (5) mated, and (6) gravid females (Figure 4). All stages refer to females only. Under laboratory conditions, the durations of these 6 stages were 2, 8, 2, 2, 2, and 4 days, respectively (Figure 4). In the field, A. gambiae can lay up to 12 batches of eggs [44]. A. gambiae females produce a batch of eggs every 3 days when given regular access to blood meals [45]. For the purpose of this model we assumed that once a gravid female has laid her eggs, she is similar in state to a mated female (i.e. she has sperm and is motivated to search for a blood meal). The arrow from the gravid to the mated state in Figure 4 reflects that females can lay multiple batches of eggs.
The laboratory life cycle of Anopheles gambiae. There are six stages in the life cycle of A. gambiae: eggs, larvae, pupae, virgins, mated, and gravid females. All stages refer to females only. At the end of the 4 day oviposition period, the gravid females return to the mated state. The parameters of the life cycle include: the proportion of eggs that hatch (p.hatch), the proportion of larvae that pupate (p.pupate), the proportion of pupae that emerge as virgins (p.emerge), the proportion of virgins that are mated (p.mate), the proportion of mated females that take a blood meal (p.blood) and that survive digesting the blood meal (p.surv.blood), the proportion of females that survive the oviposition period (p.surv.ovip), the total number of eggs produced (eggs.tot), the proportion of eggs that are laid (p.lay), and the proportion of female eggs (p.fem).
There are 10 parameters in Figure 4 (defined in Table 4) that describe the transitions between the six stages of the life cycle. We used the data from Hurd et al. [13] to estimate 7 of these life cycle parameters for each of the 27 combinations of group, environment, and genotype (see Additional files 1 and 2). For each of the 27 combinations, Hurd et al. [13] obtained one estimate of fertility from the first batch of eggs and we used this estimate for all batches. Hence our model assumes that female fertility was constant over time. Hurd et al. [13] did not estimate the other three life cycle parameters: the probability of successful pupation (p.emerge), the probability of mating (p.mate), and the sex ratio of the offspring (p.fem), so, for every experimental combination, we set these parameters to 0.9, 0.9 and 0.5, respectively. The justification for these parameter values was as follows. In the selection lines used in this experiment, the percentage of pupae that emerge as adults is ~90% (Maarten Voordouw, personal observation), hence we set p.emerge to 0.9. Hurd et al. [13] found that female insemination was greater than 90% after 3 days of mating, hence we set p.mate to 0.9. A sex ratio of 0.5 is a reasonable estimate for A. gambiae, which has sex chromosomes; hence we set p.fem to 0.5. Because these life cycle parameters were kept constant they cannot contribute to differences in λ among the factors of interest (group, environment, and genotype).
The characteristic equation to estimate λ of A. gambiae
To model stage-classified population growth over discrete time, we chose a time interval of 1 day. Hence, all estimates of the population growth rate (λ) will have units of day-1. The life cycle graph in Figure 4 represents a system of linear difference equations that describe the changes in abundance of the six A. gambiae stages over time. These linear difference equations can be written as a stage-classified matrix where λ is the dominant eigenvalue. Alternatively, these equations can be transformed into a power series in λ using the z-transform [12]. This power series is known as the characteristic equation of the life cycle and it can be solved numerically for λ [12]. To obtain the characteristic equation, we created the z-transformed life cycle graph (panel 1 in Figure 5), where the transitions between stage i and stage i+1 are time-lagged by dividing them by λTi and Ti is the duration of stage i. We reduced the z-transformed life cycle graph to its simplest form (panel 5 in Figure 5) following the permissible reductions in Caswell [12] to obtain the characteristic equation:
The characteristic equation of the life cycle of A. gambiae. The life cycle graph is reduced in five consecutive steps. In panel 5, the equation is set to 1 and λ20 - p5 *p6 *p7 * λ14 - p1 *p2 *p3 *p4 *p5 *p6 *p7 *p8 *p9 *e = 0 is the characteristic equation that can be solved for λ. The ten life cycle parameters are p.hatch (p1), p.pupate (p2), p.emerge (p3), p.mate (p4), p.blood (p5), p.surv.blood (p6), p.surv.ovip (p7), p.lay (p8), p.fem (p9), and eggs.tot (e).
We solved the characteristic equation for λ for each of the 27 combinations of group, environment, and genotype (see Additional file 2).
Stage-classified matrix of A. gambiae
We created a stage-classified matrix for the six stages of A. gambiae with a projection interval of one day. For each stage (hereafter referred to as stage i), we calculated the daily probability of survival, σi = (pi)^(1/Ti), where pi is the proportion of stage i individuals that reach the next stage (i.e. the life cycle parameters in Figure 4 and Table 4), and Ti is the duration of stage i in days. We assumed that each individual spends exactly Ti days in stage i, that all individuals in the last day of that stage (Ti - 1) graduate to the next stage, and that the age distribution within the stage is stable (equation 6.100 in [12]). These assumptions and our estimates of λ (from the characteristic equation) allowed us to calculate γi, the proportion of individuals in the last day of stage i that graduate to the next stage (equation 6.101 in [12]; see Additional file 3). We used our estimates of σi and γi to calculate Gi and Pi, which are the daily probabilities that an individual either graduates to the next stage or remains in the current stage (using equations 6.97 and 6.98 in [12]; see Additional file 3). The values of pi, Ti, σi, γi, Gi and Pi are shown in Additional file 3. We created a stage-classified matrix for each of the 27 combinations of group, environment, and genotype (see Additional file 4). We used these matrices to conduct sensitivity and elasticity analyses following Caswell [12].
For each of the 9 combinations of group (black, red, green) and environment (uninfected, infected, infected & stressed), Hurd et al. [13] blocked the three genotypes (unselected control, refractory, highly susceptible) by feeding them on the same mouse (see Additional file 1). This was done to control for variation among mice in gametocyte density and hematocrit levels.
All statistical analyses were done in R version 2.7.0. The λ values were normally distributed. We modelled λ as a linear function of the three factors: group, environment, genotype and their interactions. We ran all possible models except for the full factorial model because there were not enough degrees of freedom. We used Akaike's information criterion (AIC) to guide model selection. The best model was within 1 unit of the lowest AIC score and had the fewest number of parameters. For the best model, we used F-tests to test the significance of the factors and interactions included in the model. For the factor genotype, we used two planned contrasts to test two different hypotheses about λ. The first contrast compares the mean λ of the unselected control genotype with that of the selected genotypes (i.e., the refractory and highly susceptible genotypes combined) to test the hypothesis that selection reduced λ (e.g., due to inbreeding). The second contrast compares the mean λ of the refractory genotype with that of the highly select genotype to test the hypothesis that the evolution of Plasmodium-resistance reduced λ (e.g. due to pleiotropy).
To determine which life cycle parameters were causing the differences in λ among genotypes we used pair wise t-tests to compare the 7 life cycle parameters for each pair of genotypes (unselected control – refractory, unselected control – highly susceptible, highly susceptible – refractory). We did not compare the other 3 life cycle parameters (p.emerge, p.mate, and p.fem in Table 4) because these were constant among genotypes. To correct for multiple comparisons we set the significance level at 0.05/21 = 0.002. The utility of this approach to determine which life cycle parameters are causing the differences in λ is limited because the parameters are in different units. To account for this problem, we also compared 9 of the 13 matrix entries after scaling them by the sensitivities of the average stage-classified matrix. This scaling ensures that all the matrix entries are in units of λ. For the pair wise comparison of the scaled matrix entries, the emphasis is on the direction and magnitude of the difference between pairs of genotypes rather than the statistical significance. We did not compare the matrix entries p33, p43, p44, and p54 because these are derived from the life cycle parameters p.emerge and p.mate (see Table 4), which are constants and therefore cannot contribute to differences in λ among genotypes.
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The original experiment published in Hurd et al. [13] was supported by Wellcome Trust grants 061081 and 069162 to HH and Paul Eggleston. An NSERC of Canada Discovery grant to BA provided financial support for MJV to re-analyze the data and write the manuscript. Thanks to Parris Humphrey and two anonymous reviewers whose comments improved the manuscript.
Department of Biology, University of Victoria, PO Box 3020, Station CSC, Victoria, British Columbia, V8W 3N5, Canada
Maarten J Voordouw & Bradley R Anholt
Centre for Applied Entomology and Parasitology, School of Life Sciences, Keele University, Staffordshire, ST5 5BG, UK
Pam J Taylor & Hilary Hurd
Maarten J Voordouw
Bradley R Anholt
Pam J Taylor
Correspondence to Maarten J Voordouw.
MJV conceived the idea to re-analyze the data of Hurd et al. (2005) using matrix population models, analyzed and interpreted the data, and wrote the manuscript. PT conducted the original experiment and collected the data published in Hurd et al. (2005). BA and HH helped to interpret the data and write the manuscript. All authors read and approved the final manuscript.
Additional Table 1
Additional file 1: . The life table data of Anopheles gambiae from the study by Hurd et al. (2005). (DOC 118 KB)
Additional file 2: . The laboratory life cycle parameters of A. gambiae (see Figure 4). (DOC 97 KB)
Additional file 3: . The matrix entries for the stage-classified population matrices of A. gambiae. (DOC 480 KB)
Additional file 4: . The stage-classified population matrices of A. gambiae. (XLS 72 KB)
Voordouw, M.J., Anholt, B.R., Taylor, P.J. et al. Rodent malaria-resistant strains of the mosquito, Anopheles gambiae, have slower population growth than -susceptible strains. BMC Evol Biol 9, 76 (2009). https://doi.org/10.1186/1471-2148-9-76
Life History Trait
Population Growth Rate
Susceptible Genotype


The Indiana governor's smooth and measured performance had GOP voters wishing Mike Pence was at the top of the Republican ticket.
FARMVILLE, VIRGINIA — Virginia Senator Tim Kaine and Indiana governor Mike Pence met in the first and only vice-presidential debate on Tuesday, with the GOP No 2 handily defeating his opponent.
Pence spoke more like the smooth and measured statesman that his shouty running mate is not. He calmly articulated GOP positions on taxation, the growing debt and national security, offering a credible alternative to the current Republican standard bearer.
Pence was effective running lines of attack that Donald Trump fumbled in the first presidential debate. He hit the Clinton Foundation for its conflicts of interest. He tweaked Hillary Clinton for jeopardizing national security by setting up an authorized e-mail server.
Several times, Tim Kaine resorted to pre-canned lines on Trump's failure to release his tax returns, but never drew blood.
Kaine was more effective in getting Pence to parse and Trump-splain some of the Donald's wilder comments, such as whether 16 million immigrants would be deported (nonsense, says Pence) or whether Trump had, in fact, understood that Russia invaded Crimea (Pence insists this to be the case).
Vice presidential debates are largely meaningless. They rarely influence the general election. But we can't help wonder what this contest would look like with Pence at the top of the ticket. Clinton is fortunate she's facing Trump and not Mike Pence.


Memories eh? - clearing out my room I came across an old photo of my mum and dad taken at an office "recruitment do" in the early-seventies (my dad is now 66 bless him!) when they performed that old Beatles' fave "When I'm 64" and it got me thinking "how things have changed since then and even more how much recruitment has moved on since then! I got to wondering what our industry would look like in 2046 when I reach the grand old age of 64 as compared to how it was in the year I was born, 1982!
And this is what I came up with…. (Humour me please but it defiantly makes you think especially when our industry has changed so much and the job is definitely getting harder!
Not an exhaustive list I know but can you imagine?! This puts us all in a dilemma! As technology develops how do we combine the traditional personal approach of "working with people" with utilising technology to resource, connect and speed up recruitment processes. I'm sure you'll agree as a candidate or client sometimes the whole job board black hole can be a daunting prospect – you put your CV or job out there and hope that the right people see/apply and it's all a bit impersonal and often we find many candidates feel like they disappear into cyber space when they apply for roles with no feedback or guidance.
So we are encouraging our candidates to come in and register, and meet us face to face – to spread the word that if they come to an agency they will get the "human touch" where we will listen, support and guide them to our clients who we also "build relationships with" on a personal face to face basis.
"Will you still need me (your recruiter), ….When I'm 64?" ……. I'm hoping you will agree!!!!!!!


Besides tasty local dishes, guests love the luxurious way of life and the numerous leisure, sport and relaxation options.
Our Romantik Hotel Platte, steeped in tradition, is located in an idyllic position among the rolling hills of Southern Sauerland, surrounded by forests and meadows and close to the romantic Lake Bigge. The 6th generation of the Platte family preserves the charming atmosphere of times gone by for their guests in Attendorn.
Besides the special Westphalian delicacies from the kitchen, guests can enjoy the finer things in life and take part in the many different recreational activities available. Our riding centre provides offers to suit everyone, from the youngest to the most experienced riders. The 18-hole Golfpark Repetal is based directly opposite the hotel and cannot fail to impress golfers.
One of the largest dams in Germany (7 km) attracts numerous water lovers to its banks in the summer. Beautiful walking and cycle paths are to be found all around the "Sauerländer Meer". Or perhaps you'd like a boat trip? Then it's all aboard the "Weisse Flotte".
Golf? Just across the road is an 18-hole, par-72 golf course, one of the most beautiful in North Rhine-Westphalia.
Golfen? Einfach die Platte-Allee überqueren, 18 Loch, 72 Par, einer der schönsten Plätze in Nordrhein-Westfalen.


Our furnished Rooftop, open throughout the year, can be used by guests to relax away from the chaos of the city, while enjoying one of the most stunning views of the Eternal City: romantic rooftops, the Colosseum, the Imperial Fora and the magnificence of Archaeological Rome; the massive basilica domes and, in the distance, the Castelli Romani hill towns.
After a long day visiting Rome's treasures, the terrace bar, open from March to November, is the ideal place to relax and refresh with excellent cocktails, nibbles and snacks.
During the months the bar is closed, guests can use the outside phone to order their drinks from the Hall Bar, which will then be brought to you on the terrace by our staff.


I hate to start a blog war, but maybe there's one going on. The recent PASS 2009 election concluded a couple days ago and 3 new board members were elected.
That's 3 from 4 candidates, which is a little silly, IMHO opinion. As Geoff Hiten said in his PASS Fail post, "The problem is four people and three positions is a final round of musical chairs, not a board election." I tend to agree with it, and I've looked on in past years with a wary eye when I've seen three candidates for three positions (or two or four). That's not even an election. It's an engineered outcome.
To be fair I haven't been involved in the election process, and perhaps there were years where only 3 people submitted applications.
Kevin Kline wrote a response on his blog about the nomination committee, the process, and the history. I think he make some great points in some areas, but misses the boat, or maybe steers it in a different direction in others.
I don't think the nominating committee deliberately is seeking to do things poorly, or mislead the community. But I also don't think they're doing a good job. I know it's a job, and I appreciate the efforts, but being a volunteer doesn't excuse you from accountability, nor from poor performance.
Let me wander off the path for a moment. I worked for a guy years ago and we were examining a project that wasn't going well. We were debating if we should continue on, what changes to make, or if we should scrap it and start over in a different way. One of the people in the room said that we couldn't scrap it because we'd spent $200,000 on the project.
The guy I worked for said that was stupid. The $200,000 was gone, and we needed to move forward right now. Whether we continued on and fixed things or started over, the $200,000 didn't matter. We needed to make decisions about our expenses and direction from this point.
PASS as an organization needs to do that. It's helpful to look back at history and learn, but you cannot use history as an excuse for a lack of progress right now. To be successful, to have credibility, and to meet the needs of the community, the organization needs to disclose information on a regular and timely basis, and be accountable for mistakes and mis-steps.
The election process is a perfect example. How and why were these 4 of the 11 (or 12, can't remember) picked? What scores were used? Not to harp on Tim Ford, but how is he not qualified to be on the slate? I just don't get it. He's passionate, he works for PASS, he's intelligent. Whether or not he can answer questions to the nominating committee's satisfaction in the interview seems wrong to me. As much as I like and respect the members of the committee as technologies, I'm not sure they're eminently qualified to make that judgement.
And why aren't we, the members of PASS qualified to decide? Does the board of pass and the Nominating Committee think that we can't decide who's a good candidate? We can't judge someone's ability to articulate themselves in a paper or interview? Heck, it's the age of YouTube and blogs. Publish the applications, and the responses to the interview.
That's what an election is. It's a choice, of the people (or populace), and the most popular ones, the ones with the most votes, get to serve. If we elect a bad candidate, then we deal with that, but we have minimal requirements, we publish those (something PASS hasn't done) and then we allow debate, discussion, stumping, recommendations, etc.
I disagree with Andy Leonard's litmus test for a board candidate, but I'm willing to listen to his ideas. At least he's publishing his thoughts on the matter, and giving us a reason not to vote for Matt Morollo. I don't agree with his reason, but I'm willing to listen.
When we elect leaders in government, there is plenty of debate, opinion, blogging, tweeting, etc. about their positions and thoughts. Why not here? Couldn't PASS do a series of interviews like Brent Ozar? Or at least link to relevant items from people writing about the election? I would think that would be easy to do. Maybe even allow members to post links to articles and blogs themselves?
There are many complaints I've had of PASS over the years. To a large extent I've questioned what the point of it is at times. Why not just let Microsoft run a SQL Server conference every year? A lot of years I don't think PASS has done much else.
Last year PASS introduced the PASSPort, a social networking idea to try to get members linked to each other. I think the concept failed, which isn't a bad thing, but what has been done in the meantime? With the tremendous amount of tweeting during the Summit last year, how can the board and management company not expect wide, and extremely real-time, discussion of what happens?
The election ended on Tuesday noon, PST. I check the web site for PASS, saw no mention of the winners, and then noticed the they would be announced on Wednesday. At noon, PST.
We are SQL professionals, and while we might get mired in details, can any of us think of a reason to not announce the results as 12:01PST on Tuesday? We elect, arguably, the most powerful man in the world through a process where votes are tallied and we can see the candidates' success in real time. A winner can be "announced" even with all the votes not in. The four candidates in this game of musical chairs are probably waiting and watching. There's no need to contact them, no press release, no messaging needed. Just put the results of the voting up there.
Heck, give them to @BlytheMorrow. I think a tremendous number of PASS members follow her. She can post it and we'll spread the word, no effort from PASS needed.
It's a small thing, but it's an example of where the board is behind the times. They're not in touch with the members, and don't (appear) to be willing to serve the electorate in an open manner. We had a similar issue with the choice of speakers for the Summit, when choices weren't disclosed in a very timely manner.
I live in the SQL community every day. On Twitter, Facebook, through blogs, articles, and I'd like to think that I'm one of the few people whose job it is to keep a finger on the pulse of the community. I'm fortunate in that way because like Brent Ozar, it's my job to do so. I can interact with lots of people regularly without taking time away from other work. Or at least I can do it with a good excuse.
I have seen almost no publications, no releases, no accountability from the PASS board about what they have done for us. The highlights of the past year, from PASS, seem to be the conference, and the 24 Hours of PASS. Beyond that, I've seen very little transparency that explains what has been done.
What were the goals for 2009? Were they met? If so, what happened? If not, what happened?
It's accountability, and transparency. It lets us know if we made a good decision electing board members, it lets us know where and how to give feedback. Without it, I, and many others, feel that PASS is not serving the community, and possibly not even acting ethically.
Are the board members enjoying the prestige and benefits of being on the board without actually doing anything? I'd like to think not, but I have no idea. I almost never see them update us, or disclose, what they've done.
To some extent, I think it's my fault. Not just me, though. It's also the rest of the community that has not demanded accountability. We as a group have not questioned enough the way that PASS has been run.
I'll take a large share of the blame as I've been hesitant to write about some of the issues with PASS. I do business with them with the opening night party, and I know most of the board, past and present. They're friends, colleagues, and I haven't wanted to publicly denounce their efforts.
Publish what you do, and why you do it. Every board member, and at least the head of the management company needs to regularly publish what they do. And why. Be accountable, take responsibility for your actions, or inactions. Be transparent.
Get involved, you don't have to commit to run the Standard, as Grant has, but do something. Give feedback to PASS. Comment on what they're doing. Let them know what you like, what you don't, and what you want. Post publicly when you don't like something, and more importantly, post about the things you DO like. Volunteer if you can, run for the board if you want to, but at least give your opinion to the community a couple times a year.
I believe in PASS, and I hope I've convinced a few of you to do the same. I've also written an editorial today asking what you might want from PASS. Feel free to give your opinion there as well.


text:
Solar Frontier Americas Acquires Canadian Solar's 210 MWp Mustang Two Solar Project
GUELPH, Ontario, and SAN FRANCISCO, Dec. 18, 2018 /PRNewswire/ -- Canadian Solar Inc. ("Canadian Solar") (NASDAQ: CSIQ), today announced its wholly owned subsidiary Recurrent Energy LLC ("Recurrent Energy") has completed the sale of its 150 MWac/210 MWp Mustang Two solar project to Solar Frontier Americas ("SFA").
"The Mustang Two transaction is the latest example of the strong demand we see globally for Canadian Solar's high quality solar assets, given our ability to partner at various points in a project's development," said Shawn Qu, chairman and chief executive officer of Canadian Solar. "We are pleased to partner in this transaction with Solar Frontier Americas, given its extensive solar project development and construction experience."
Located on 1,400 acres in Kings County, California, the Mustang Two project is expected to create approximately 400 jobs during peak construction. In this partnership, Recurrent Energy will continue to manage the development of the project, readying it for construction; Solar Frontier Americas will finance and manage the construction of the project, which is slated to achieve commercial operation in 2020. The project will then be operated by Solar Frontier Americas' growing independent power producer ("IPP") business.
"With this important acquisition, SFA further expands its U.S. business to become an independent power producer, an owner of operating electric power facilities," said Charles Pimentel, CEO of Solar Frontier Americas' IPP business unit. "We already have a substantial greenfield pipeline and are actively acquiring utility-scale projects and development assets to further scale our business."
Once the project is operational, the energy generated by the solar power facility will be split between two long-term power purchase agreements: Peninsula Clean Energy (the community choice energy agency which serves San Mateo County) is contracted to receive 100 MWac, and the Modesto Irrigation District will acquire 50 MWac. The combined energy generation from the two PPAs will power 37,500 homes with clean electricity.
About Solar Frontier Americas
Solar Frontier Americas, a U.S. based subsidiary of Showa Shell Sekiyu K.K. (a global energy solutions company), is a growing independent power producer, solar developer and module supplier. The vertically-integrated energy company acquires, develops, owns and operates high yield utility-scale solar power generation plants; selling the clean energy to help communities both economically and ecologically live in healthier environments. With offices in California and Nevada, SFA continues to develop its growing pipeline of over 1 GW of utility-scale projects. Part of a longstanding organization recognized internationally for their dedication to excellence in quality and service, SFA continues that tradition in their North American renewable energy business. Learn more at www.solar-frontier.com.
Recurrent Energy is a leading utility-scale solar and energy storage project developer, delivering competitive, clean electricity to large energy buyers. Based in the U.S., Recurrent Energy is a wholly owned subsidiary of Canadian Solar Inc. and functions as Canadian Solar's U.S. project development arm. Recurrent Energy has approximately 5 GW of solar and storage projects in development in the U.S. Additional details are available at www.recurrentenergy.com.
View original content:https://www.prnewswire.com/news-releases/solar-frontier-americas-acquires-canadian-solars-210-mwp-mustang-two-solar-project-300768028.html
Solar Frontier Americas Media Relations, Jill Hansen, Tel: +1-925-997-5956, Email: jill@hansenre.com OR Canadian Solar Inc. Contacts, Mary Ma, Manager, Investor Relations, investor@canadiansolar.com OR David Pasquale, Global IR Partners, Tel: +1-914-337-8801, csiq@globalirpartners.com OR Recurrent Energy Media Relations, Jesse Prier, Manager, Marketing & Communications, Tel: +1-415-814-1067, PR@RecurrentEnergy.com

redpajama_set_name: RedPajamaCommonCrawl


text:
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Biofortified Blog Australian seed banks in disarray
Australian seed banks in disarray
by David Tribe 1 October 2010 17 Comments
Crisis in Australia's seed banks
by Elizabeth Finkel
Cosmos Online
Australia's seed banks are hitting the dust, one by one, which may be violating an international treaty and could damage Australian agriculture down the track. (more at link)
Syndicated biofortified, Environmental management, Food security, Genetics
Written by David Tribe
David Tribe's research career in academia and industry has covered molecular genetics, biochemistry, microbial evolution and biotechnology. He has over 60 publications and patents. Dr. Tribe's recent activities focus on agricultural policy and food risk management. He teaches graduate programs in food science and risk management as a Senior Lecturer in the Department of Agriculture and Food Systems, University of Melbourne.
View all posts by David Tribe
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Eric Baumholder says:
You can tell this is a junk article pretty easily. Look at the comparison embedded in this sentence: "There are an estimated 30,000 edible species, while 60% of the world's calories are provided by just three: wheat, rice and corn."
That means, 29,997 other crops are out there, in addition to wheat, rice and corn. Ridiculous.
They're actually counting "many wild relatives" of cultivated crops as distinct species. This allows them to drastically (and disingenuously) inflate 'biodiversity' and 'endangered species' numbers.
Biodiversity is just as much a secular religion as organic farming. They'd gain more converts if they didn't fudge their numbers habitually.
Here's another howler: "
Biloela is the third seed bank to go into crisis in the last two years.
"The bank at Tamworth, NSW (wheat, barley and oats) and the bank at Horsham, Victoria (oil seeds, such as canola and legumes) are safe because they carry the commercially valuable seeds."
If a seed bank is involved in things that are not commercially valuable, that means they're storing weed seeds, instead. So then the central question is whether, and how much, we should invest in preserving 'endangered weeds'.
Then there's the old mantra: "many wild species are disappearing due to urbanisation, farming and climate change". Anyone who pays attention to this issue will have noted that for some reason, these species are almost never identified. And when they are identified, they never amount to what anyone would call "many".
Anastasia Bodnar says:
2 October 2010 at 12:21 pm
I strongly disagree. This article was quite well written, explaining the value of seed banks and discussing the difficulty of maintaining germplasm.
It's true that "biodiversity" has become another catchphrase, something that people generally think is good without knowing why, and that's a shame. Being a catchphrase isn't enough, obviously, since countries keep closing their seed banks. Thankfully the US still has a strong germplasm resources system, but who knows how long funding will stick around.
The thing is, seed banks are extremely important. As I mentioned in my comment on "When our friends lie", germplasm has definitely been very useful to small and large breeders alike when it comes to maize, but maize isn't the only one. Most crops started with a fairly small breeding base, so to find new genes for things like disease resistance and environmental tolerance we must look to landraces or wild relatives. So many of these wild relatives and landraces haven't been collected yet, so we either have to collect them ASAP or preserve them in situ.
If you have a chance, browse around the Agricultural Biodiversity blog. You'll find tons of examples of why ag biodiversity, including preservation of wild relatives, is very important. The authors are friendly and will respond to comments.
Finally, I just have to address your comment "If a seed bank is involved in things that are not commercially valuable, that means they're storing weed seeds, instead." There are a lot of crops that aren't commercially valuable that are nonetheless very important. Just one = cassava. Another reason to keep these as-yet not commercially viable edible plants around – someday the current edible plants won't work any more. For example, Ug99 has the potential to wipe out wheat as a valuable crop. What then? Perhaps other small grains that aren't currently valuable on a large scale basis could be grown instead, things like amaranth, sorghum, or barley.
Anastasia,
I will strongly disagree, in turn. The notion that there are 29,997 crop species that are not wheat, rice and corn, means these species are not sexually compatible with wheat, rice and corn.
Being gracious to the author and conceding that he/she is confused, you are still stuck with the notion of preserving landraces with no discernible economic value. As the art and science of transgenesis matures, the value of maintaining a museum of abandoned cultivars is of continuing lesser significance, and eventually will become zero.
Introducing novel traits into elite germplasm is vastly superior to clumsy methods involving crosses between elite strains and weedy relatives. One scientist I know described the methods as 'pushing a chain uphill'.
Even so, there is significant value in maintaining 'seed banks', such as at Svalbard. When the gang-greens complain that vast tracts of crops are monocultures that 'threaten biodiversity', you can say, 'Don't worry, leave us alone. Your obsolete cultivars are stored safely in Svalbard. When farmers decide they want low-yielding seeds, they'll be available.'
Where exactly do you think the genes used in transgenesis come from? Occasionally they have origins in non-food species like bacteria, but many if not most genes for traits like environmental tolerance and disease resistance come from crop wild relatives. Their economic value is in providing genes for breeding or biotechnology. Beyond that, species like amaranth might not be useful now but they might be in the future. If we don't save those seeds, they'll be simply gone. Your stance seems awfully short sighted. Talk to the GEM program about how obsolete all their tropical maize varieties are. Ask about teosinte, tripsicum, and other maize relatives.
I appreciate your patience, yet must still disagree. After thousands of years of selective breeding, recently augmented by marker-assisted selection, we're very near the limit of what can be done with what can be found within the wheat, rice and corn genomes. As these efforts proceed, it is increasingly less likely that a (trans)gene of interest will be found to 'already be there'.
Meanwhile, the genomes of wheat, rice and corn, and their 'wild/weedy' relatives are a mere drop in the bucket compared to the genomes of everything else on the planet. If you look at that ratio, the likelihood that a gene of interest will be found in an 'unrelated' species is astronomically greater than the likelihood of finding it within its own species. Conversely, there is nearly 100% certainty that the gene of interest will be found in an 'unrelated' species.
That leaves us with the question of why we should preserve seeds which are, admittedly, not commercially valuable. Thankfully, the answer to that is quite simple. These efforts are supported by those who insist that we don't need genetic engineering, because all sorts of valuable genes are all still hidden in obsolete cultivars, just waiting to be found and used in breeding programs. Such claims are not well-founded. When not motivated by antipathy toward genetic engineering, they merely appeal to the wistful notion of the beauty of antique agriculture and how the seeds encapsulate the indigenous wisdom of farmers/'seed-savers' who in past eras enjoyed a mystical connection with Nature.
That said, I would draw your attention to a new development in insect-resistant cotton. [1] What are the odds of finding the gene(s) of interest in a collection of obsolete cotton seed? Vanishingly slim.
1. Coexpression of potato type I and II proteinase inhibitors gives cotton plants protection against insect damage in the field. Proceedings of the National Academy of Sciences, Published online before print August 9, 2010, doi: 10.1073/pnas.1009241107. Available at: http://www.pnas.org/content/107/34/15011.full
Karl Haro von Mogel says:
It is not just for the development of new varieties for commercial production that germplasm in seed banks has value. It is also necessary for basic research, the kind of basic research that teaches us about the plant genomes that we intend to modify. For instance, the origin of the variant of the gene I am studying was tied down to an accession in a seed bank. So even if seed banks become less important for breeding elite cultivars, it will still remain crucial to basic research. You will find a lot of agreement with me on this, I could just walk down the hall and survey a slice of plant breeders (non-mystical types) and ask them if they think seed banks are not worth the money and I'll bet you that my data will be 100% in disagreement with your assessment with a standard deviation of zero.
That being said, I agree with Anastasia that you are wrong about the value of seed banks for breeding purposes, and will offer up another example. My own gene, sugary enhancer, makes a sweeter sweet corn. But to make it actually taste good, I hear it takes about five or six other genes that work with it. Genetic background is about as important as major genes for breeding. As we start getting into complicated engineering projects that tweak developmental genes, genetic background is going to be increasingly important. Let's say a gene that makes field corn produce five ears per plant doesn't work well in today's elite germplasm, and breeders have to go back to some line of corn from a seed bank to get the right genetic background to take full advantage of this trait. This would not be possible without the bank that holds onto the genetic variation currently present in the species.
I will be presenting a graduate student seminar on apomixis in maize in November, and one of the papers I will be talking about involved crosses between maize and tripsacum. If we can make corn produce genetically identical seeds through apomixis, then we would have 'fixed' heterosis (hybrid vigor), which would be a remarkable achievement. Unless of course, you favor tossing those accessions 'of no discernible economic value' out the window.
"The notion that there are 29,997 crop species that are not wheat, rice and corn, means these species are not sexually compatible with wheat, rice and corn." This is not true. There are plenty of things that aren't 'wheat rice and corn' that are sexually compatible with those crops. And for polyploid crop species like wheat, the diploid genomes of ancestors and relatives are useful for introducing important genes into modern varieties today. Check out Jorge Dubcovsky's work on enhancing the protein, iron, & zinc content of wheat.
Eric, let me know when the seed banks stop actually providing valuable genes and then we can talk about obsolescence.
Of course Eric is correct. We don't need wild wheat because we've solved rust issues once and for all. And social-economic catastrophe will never shake the dominant food supply. We'll never have an event like WW II again, and so local and wild food species are completely useless. A country like Greece will never face starvation and forage for and collect wild greens to stave off malnutrition. Africans will avoid millet and teff as chickens fed on African produced soy protein become the norm. And those darn Peruvians will stop eating those nasty nasturtium related mashu crops and oxalis oca crops. Finally, wheat and corn and rice and soy will reign supreme and those foodies who insist that they have highly developed diverse palletes will be reduced to eating "infusions" of flavor into soy based components.
We've learned and done it all in the 50 years post Watson and Crick, and any varietal developed prior to that date is no better than eating yesterday's scraps. For that matter, let's recycle Shakespeare's worthless tomes so we can print something modern and useful, say Lady Gaga lyrics? Certainly the paper used for the bible and koran could be put to better use, after all, we have Dr Laura and Oprah to guide our souls. Paper makes good fire starter for burning libraries as a whole – dusty repositories of facts proved fiction.
History is a clear linear path of progress and ADM will be supermarket to the world for all times to come. Middle Ages never occurred and claims opposing this are no more than a marketing schemes cooked up by anti-progressive activists trying to make a buck. It's been progress from day one, and conservators are nothing but scat collectors fetishizing a dead and useless past.
All that satire aside, I do agree in situ genetic stewardship is the best way to go, and do think that many gene banks make exaggerated claims in desperate attempts to gain funding. There may only be 10,000 wild and cultivated food species, maybe only half that. People make desperate inflations when faced with denialists of history, who arrogantly want to pretend we have it all figured out now. yes, we have made great progress in the last 50 years – but really – what makes you think that we've assessed the genetic diversity of our food crops and that the bank is almost empty, and that "Conversely, there is nearly 100% certainty that the gene of interest will be found in an 'unrelated' species" – where do you get that certainty??
You've shown your true stripes sir – black and white and poorly read all over. Perhaps consider adding to your library a few history books. Or even one on crop genetics.
David Tribe says:
The very reason we need to preserve biodiversity is shown up by Eric's comments. The environment is very diverse and the plant responses complex and we don't understand all the requirements for future success. We need to keep as many options open as possible when we don't fully understand the future.
Making some options (GM) too expensive than necessary by overegulation closes down other options like seed banks, as it decreases available investment resources.
Karl,
Anything you say about the value of basic research works for me. It should, for anyone.
That bit aside, pointing out the commercial value of old cultivars has little to do with my point about preserving cultivars with no commercial value.
Of course there is value in apomictic maize, which would be something worth preserving in the accessions if it has been proven to exist among them. Same with perennial maize.
As for the rest — I would suspect the Vavilov saga inspires many of those involved, but the majority of landraces involved are not worth dying for, certainly not when superior technology is available.
And, considering that the insect and microbial pests and weeds associated with the cultivation of wheat, rice and maize have co-evolved with those crops, it's nearly mandatory to look outside the crop genomes for the genes and traits of interest.
Even so, I understand the necessity of throwing a sop to the greenpeacers; tremendous calamities could easily ensue from agreeing with these points.
I very nearly despaired of agreeing which you, but I do. Very nearly.
The value we place on antique cultivars is inversely related to our understanding of plant genomes and transgenesis. When both are fully understood, the value of seed banks will crash and the putative value of what is preserved at Svalbard will be viewed as a betrayal of what humans need in the imaginary time of crisis.
You are absolutely right. The more onerous the regulations of transgenic crops become, the more valuable become the outdated cultivars. But there is a limit, and I submit, the limit of 'gene-mining' those old, clumsy (top-notch, for their time) events has very nearly been achieved.
Ewan R says:
I'm going to add to the general disagreement with Eric's statements –
As the art and science of transgenesis matures, the value of maintaining a museum of abandoned cultivars is of continuing lesser significance, and eventually will become zero.
Maybe in 50 or 100 years we'll just be able to get plants to do whatever we want transgenically without a reference library to pull from – there are far too many abandoned cultivars and wild relatives (and sub-types thereof) to expect complete knowledge of how they work in my lifetime at least – and our current knowledge of genomics, proteomics, transcriptomes, ionomes (and any other omes I've omitted) is so sparse as to make it nigh on impossible to predict or model exactly what a given gene will do in a given germplasm – remove the supply of seed from diverse species and varieties of species and you remove the capacity to mine these genomes for useful candidates in the future (good luck generating transcriptional libraries under various growth condition for a variety that no longer exists – maybe in a century it'd be modelable from genome information alone, but I doubt it)
It's also pretty foolhardy imo to use the all eggs in one basket approach, relying solely on transgenics to resurrect old traits (working on introducing traits to corn I'm often rather jealous of how much breeders can still do, and of the fact that if they manage a 1-2% increase in yield, or a 7/10 win ratio in the field)
'gene-mining' those old, clumsy (top-notch, for their time) events has very nearly been achieved.
Based on what exactly? As far as I'm aware even for varieties of corn we're still only really looking at a handful of varieties in very broad terms (B73, Mo17 and whatever else Hirel et al work with) without any real clarity on the horizon – I'd assume that other crops are in about the same position – Tolenaar did a lot of pretty cool work on hybrids across generations at a crop physiology level but afaik never drilled down to individual plant level never mind genomic differences etc – we're still gene-mining arabidopsis, the day we can say we're done with old cultivars of even the top 3 crops is, in my mind, scheduled well after I retire (and likely after my 2 week old son retires)
That leaves us with the question of why we should preserve seeds which are, admittedly, not commercially valuable. Thankfully, the answer to that is quite simple. These efforts are supported by those who insist that we don't need genetic engineering, because all sorts of valuable genes are all still hidden in obsolete cultivars, just waiting to be found and used in breeding programs.
Who are any of us to judge what is commercially valuable in a field that is so poorly understood? I'm pretty pro-GE (by essentially anyones standards) and I wouldn't be surprised in the slightest if transgenes from teosinte, or from a 1930's corn inbred were the leading commercial traits in 30 or 40 years time (I equally wouldn't be surprised if these traits came from deep sea vent organisms, E.coli, or essentially any other organism (although animal origin would surprise me b/c nobody will touch those with a 15′ barge pole for fear of bad PR)) – I'd be incredibly upset if the reason given for not testing a gene was because it was from a non-commercial viable variety as it completely doesn't follow that b/c the varieity isn't great anymore that any individual mutant allele (for instance associated with resistance to a disease) or pattern expression for a given gene couldn't be useful in elite hybrids.
Ewan,
I would like to hear from you about ongoing projects to sequence the many accessions of, i.e., maize cultivars which reside only in gene-banks. If those claimed to be 'of no commercial interest' (quoting the original article) are nonetheless as valuable as you suggest, such projects would be rampant and aggressive.
However, with the planetary genome — a mundane miracle which allows a gene from somewhere to function in something vastly elsewhere — it is orders of magnitude more likely that a gene of interest will be found in a sexually-incompatible organism, than in a genome (maize) that's been kicked about and rebundled over and over for about 6,000 years.
Your projection of the utility of transgenesis surging to the fore in perhaps 50-100 years appears not to take into account what Craig Venter has achieved with 'synthetic biology'. To be sure, Venter's project is to employ the smallest genome possible, but advances in this field will accelerate in accordance with Moore's Law.
The advances of in silico plant biology will I am sure move ahead as fast as in silico per se, barring unintended circumstances such as bio-Luddism.
c_rader says:
Eric, allow me to speculate with no data at all.
The approximate paradigm is one-gene one-protein, not one-gene one-trait. So it's likely that most traits are determined by constellations of genes and that evolution has caused genes to tend to congregate in organisms that find them useful when they coexist.
This isn't going to be absolute. But we would expect that, for example, resistance to a certain parasite could more likely be evolved as a cluster of several genes, and a cultivated variety may lack such resistance or have diminished resistance because it lacks one of the set of mutually supportive genes.
When you are talking about a simple one-gene trait, such as the ability to synthesize the cry protein that directly affects a certain pest, you may expect that trait to work over a wide range of species, genera, or families. But when a single trait is affected by many genes in an intricate dance, look for the missing gene in a closely related plant.
"Ewan, I would like to hear from you about ongoing projects to sequence the many accessions of, i.e., maize cultivars.."
Its worth noting that sequence a maize genome is a mammoth task. Its unlikely that "many accessions" from genebanks will be sequenced as this approach with possibly not be cost effective for decades.
Terry Smith says:
You saved me time in assessing your `contribution' right there. That "there are an estimated…" is a comment I have no trouble accepting – I've got about 25 of them in my back `lawn', though I haven't had to make bread out of kikuya roots as yet.
I see nothing that makes the claim of how many are cultivated as crops.
Looking on the bright side, there's a little piggie somewhere who may have to build his house of bricks.
You can indeed. I have at least 25 edible species in a square meter of my back yard, though I haven't felt the need for kikuya root bread yet. Nowhere does the author claim that there are 30,000 _crops_. Somewhere there is a little piggie who needs to build his house of bricks.
Thank you for flagging your `contribution' so early. As you noted – ridiculous.
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text:
Metabolic acid-base disturbances in patients in the emergency department
EM Antonogiannaki1,
E Lilitsis1 &
D Georgopoulos1
The aim of the present study is to determine in unselected patients that visit the emergency department whether the physicochemical approach improves the ability to diagnose acid-base disorders compared with the two commonly used diagnostic approaches; one relying on the plasma bicarbonate concentration (HCO3-) and anion gap (AG), and the other on the base excess (BE).
A prospective observational study took place in the emergency department at a university hospital during the period of March to September 2011. Three hundred and sixty-five patients were included. Arterial and venous samples were drawn for blood gases and a serum biochemical panel, respectively. The decision to collect arterial samples was made by the attending physician in the emergency department who was not involved in the study.
All patients were admitted to the hospital, while 103 of them (28%) were transferred directly to the ICU. Hypoalbuminemia (serum albumin ≤35 g/l) was observed in 191 patients (52%). The BE and HCO3- were normal in 35% and 38% of the total patients, respectively. The corresponding values in patients admitted to the ICU were 41% and 28%. In a significant proportion of patients in whom BE and/or HCO3- were normal the physicochemical approach detected the presence of acidifying and/or alkalinizing disturbances. Hypoalbuminemia (metabolic alkalosis) was identified in 45% of patients with normal HCO3- and 48% of patients with normal BE. Strong ion difference (SID) acidosis (SID ≤36 mEq/l) was observed in 49% and 44% of patients with normal HCO3- and BE, respectively. A high unmeasured strong ion concentration ([XA-] ≥8 mEq/l, metabolic acidosis) was observed in 48% of patients with normal HCO3- and in 52% of patients with normal BE. Patients in whom hidden acidosis of high unmeasured strong anion type was observed were identified by the common diagnostic approach only using the AG adjusted for hypoalbuminemia (AGadj ≥13 mEq/l). Patients who were admitted to clinical wards with acidosis, other than hyperchloremic, remained significantly more days in the hospital than those without the disturbance.
Hypoalbuminemia is a common finding in patients in the emergency department and complicates the interpretation of acid-base data using the common diagnostic approaches. A physicochemical approach may better identify metabolic disturbances in this population.
University Hospital of Heraklion, Greece
EM Antonogiannaki, E Lilitsis & D Georgopoulos
EM Antonogiannaki
E Lilitsis
D Georgopoulos
Correspondence to EM Antonogiannaki.
Antonogiannaki, E., Lilitsis, E. & Georgopoulos, D. Metabolic acid-base disturbances in patients in the emergency department. Crit Care 16, P149 (2012). https://doi.org/10.1186/cc10756
HCO3
Metabolic Acidosis
Base Excess
Metabolic Alkalosis


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