Dog Life Spans and the Evolution of Aging.

AbstractThe basic tenets of the evolutionary theories of senescence are well supported. However, there has been little progress in determining the relative influences of mutation accumulation and life history optimization. The causes of the well-established inverse relationship between life span and body size across dog breeds are used here to test these two classes of theories. The life span-body size relationship is confirmed for the first time after controlling for breed phylogeny. The life span-body size relationship cannot be explained by evolutionary responses to differences in extrinsic mortality either of contemporary breeds or of breeds at their establishment. The development of breeds larger and smaller than ancestral gray wolves has occurred through changes in early growth rate. This may explain the increase in the minimum age-dependent mortality rate with breed body size and thus higher age-dependent mortality throughout adult life. The main cause of this mortality is cancer. These patterns are consistent with the optimization of life history as described by the disposable soma theory of the evolution of aging. The dog breed life span-body size relationship may be the result of the evolution of greater defense against cancer lagging behind the rapid increase in body size during recent breed establishment.

The kin selection theory of genomic imprinting and modes of reproduction in the eusocial Hymenoptera.

Genomic imprinting is known from flowering plants and mammals but has not been confirmed for the Hymenoptera even though the eusocial Hymenoptera are prime candidates for this peculiar form of gene expression. Here, the kin selection theory of genomic imprinting is reviewed and applied to the eusocial Hymenoptera. The evidence for imprinting in eusocial Hymenoptera with the typical mode of reproduction, involving the sexual production of diploid female offspring, which develop into workers or gynes, and the arrhenotokous parthenogenesis of haploid males, is also reviewed briefly. However, the focus of this review is how atypical modes of reproduction, involving thelytokous parthenogenesis, hybridisation and androgenesis, may also select for imprinting. In particular, naturally occurring hybridisation in several genera of ants may provide useful tests of the role of kin selection in the evolution of imprinting. Hybridisation is expected to disrupt the coadaptation of antagonistically imprinted loci, and thus affect the phenotypes of hybrids. Some of the limited data available on hybrid worker reproduction and on colony sex ratios support predictions about patterns of imprinting derived from kin selection theory.

Gene dynamics of haplodiploidy favor eusociality in the Hymenoptera.

The problem of whether haplodiploidy is responsible for the frequent evolution of eusociality in the Hymenoptera remains unresolved. The little-known "protected invasion hypothesis" posits that because a male will transmit a new allele for alloparental care to all his daughters under haplodiploidy, such an allele has a higher probability of spreading to fixation under haplodiploidy than under diploidy. This mechanism is investigated using the mating system and lifecycles ancestral to eusocial lineages. It is shown that although haplodiploidy increases the probability of fixation of a new allele, the effect is cancelled by a higher probability of the allele arising in a diploid population. However, the same effect of male haploidy results in a 30% lower threshold amount of reproductive help by a worker necessary to favor eusociality if the sex ratio of dispersing first-brood offspring remains even. This occurs because when first-brood daughters become workers, the sex ratio of dispersing first-brood offspring becomes male-biased, selecting for an overall female-biased first-brood sex ratio. Through this mechanism, haplodiploidy may favor eusociality in the absence of a female-biased sex ratio in dispersing reproductive offspring. The gene-centric approach used here reveals the critical role of male haploidy in structuring the social group.

The Extension of Foundress Life Span and the Evolution of Eusociality in the Hymenoptera.

AbstractThe evolution of effectively sterile workers in the aculeate Hymenoptera (ants, bees, and stinging wasps) requires that a female's life span largely overlap that of her daughters. The evolution of long nest foundress life spans in eusocial species from the short life spans of solitary species is investigated. Analyses that control for phylogeny show for the first time that foundress adult life span increases and first-brood offspring development time decreases with increasing colony size, resulting in the ratio of foundress adult life span to worker total life span increasing with increasing colony size. These patterns support the hypothesis that the reproductive division of labor increases with increasing colony size, explaining the evolution of effectively sterile workers in species with large colonies. However, there is a discrete increase in foundress adult life span in the transition from noneusociality to eusociality that is independent of colony size. An analysis of life history characters suggests that this increase is explained by nests being founded by multiple females and progressive feeding of larvae as they develop. A reduced rate of senescence of a dominant cofoundress may be selected as a plastic response to social status if high-risk tasks performed by subordinate cofoundresses reduce the dominant's extrinsic mortality rate. Multiple-foundress nests in which one female is responsible for most or all of the reproduction (semisociality) and in which foundresses are full sisters are favored by haplodiploidy, perhaps explaining why eusociality is so common in the Hymenoptera.

Plastic Senescence in the Honey Bee and the Disposable Soma Theory.

The demonstration of life span plasticity in natural populations would provide a powerful test of evolutionary theories of senescence. Plastic senescence is not easily explained by mutation accumulation or antagonistic pleiotropy but is a corollary of the disposable soma theory. The life span differences among castes of the eusocial Hymenoptera are potentially some of the most striking and extreme examples of life span plasticity. Although these differences are often assumed to be plastic, this has never been demonstrated conclusively because differences in life span may be caused by the proximate effects of different levels of environmental hazard experienced by castes. Here age-dependent and age-independent components of instantaneous mortality rates of the honey bee (Apis mellifera) were estimated from published life tables for natural and seminatural populations to determine whether differences in life span between queens and workers and between different types of workers are indeed plastic. These differences in life span were found to be due to differences in the rate of actuarial senescence, which correlate positively with the rate of extrinsic mortality, in accordance with the central prediction of evolutionary theories of senescence. Although all three evolutionary theories of senescence could in principle explain such plastic senescence, given differential gene expression between castes or life stages, only the disposable soma theory adequately explains the adaptive regulation of somatic maintenance in response to different environmental conditions that appears to underlie life span plasticity.

Isogamy in large and complex volvocine algae is consistent with the gamete competition theory of the evolution of anisogamy.

Although the gamete competition theory remains the dominant explanation for the evolution of anisogamy, well-known exceptions to its predictions have raised doubts about the completeness of the theory. One of these exceptions is isogamy in large or complex species of green algae. Here, we show that this exception may be explained in a manner consistent with a game-theoretic extension of the original theory: a constraint on the minimum size of a gamete may prevent the evolution of continuously stable anisogamy. We show that in the volvocine algae, both gametes of isogamous species retain an intact chloroplast, whereas the chloroplast of the microgamete in anisogamous species is invariably degenerate. The chloroplast, which functions in photosynthesis and starch storage, may be necessary to provision a gamete for an extended period when gamete encounter rates are low. The single chloroplast accounts for most of the volume of a typical gamete, and thus may constrain the minimum size of a gamete, preventing the evolution of anisogamy. A prediction from this hypothesis, that isogametes should be larger than the microgametes of similar-size species, is confirmed for the volvocine algae. Our results support the gamete competition theory.

The evolution of sexes: A specific test of the disruptive selection theory.

The disruptive selection theory of the evolution of anisogamy posits that the evolution of a larger body or greater organismal complexity selects for a larger zygote, which in turn selects for larger gametes. This may provide the opportunity for one mating type to produce more numerous, small gametes, forcing the other mating type to produce fewer, large gametes. Predictions common to this and related theories have been partially upheld. Here, a prediction specific to the disruptive selection theory is derived from a previously published game-theoretic model that represents the most complete description of the theory. The prediction, that the ratio of macrogamete to microgamete size should be above three for anisogamous species, is supported for the volvocine algae. A fully population genetic implementation of the model, involving mutation, genetic drift, and selection, is used to verify the game-theoretic approach and accurately simulates the evolution of gamete sizes in anisogamous species. This model was extended to include a locus for gamete motility and shows that oogamy should evolve whenever there is costly motility. The classic twofold cost of sex may be derived from the fitness functions of these models, showing that this cost is ultimately due to genetic conflict.

Using Therapeutic Toys to Facilitate Venipuncture Procedure in Preschool Children.

Intravenous access procedures in children are considered to be one of the most stressful because it is invasive, and the use of needles generates anxiety, insecurity, and fear. Playful strategies using dolls and even the materials used for venipuncture can assist children in understanding, accepting, and coping with the procedure. Field research was developed on the applicability of the therapeutic toy in the preparation of preschool children for venipuncture procedure based on the protocol developed by Martins, Ribeiro, Borba, and Silva (2001) and Kiche and Almeida (2009). The study was done in a private hospital in Greater São Paulo, Brazil, with 10 children ages 3 to 6 years. Data were gathered through observation and questionnaires completed by the children's adult guardians. Before the activity, the children showed fearful facial expressions, used monosyllabic responses, and avoided looking at the health care professional. After the strategy of using therapeutic toy dolls and puppets, 40% of the children calmly accepted the venipuncture procedure, and 100% showed a change to their initial negative reaction, became more communicative and cooperative, and participated and interacted with researchers, even after the end of the activity and procedure. The strategy of therapeutic toys helps make an unfamiliar environment, strangers, and a procedure characterized as painful and difficult less stressful. Pediatric nurses are in a good position to use this resource to offer more humanized care to children.

Antibody selection and amino acid reversions.

Pathogens adapt to antibody surveillance through amino acid replacements in targeted protein regions, or epitopes, that interfere with antibody binding. However, such escape mutations may exact a fitness cost due to impaired protein function. Here, it is hypothesized that the recurring generation of specific neutralizing antibodies to an epitope region as it evolves in response to antibody selection will cause amino acid reversions by releasing early escape mutations from immune selection. The plausibility of this hypothesis was tested with stochastic simulation of adaptation at the molecular sequence level in finite populations. Under the conditions of strong selection and weak mutation, the rates of allele fixation and amino acid reversion increased with population size and selection coefficients. These rates decreased with population size, however, if mutation became strong, because clonal interference reduced the rate of adaptation. The model successfully predicts the rate of reversion per allele fixation for an important human immunodeficiency virus type 1 (HIV-1) antibody epitope region. Therefore, antibody selection may generate complex adaptive dynamics.

The dynamics of HIV-1 adaptation in early infection.

Human immunodeficiency virus type 1 (HIV-1) undergoes a severe population bottleneck during sexual transmission and yet adapts extremely rapidly to the earliest immune responses. The bottleneck has been inferred to typically consist of a single genome, and typically eight amino acid mutations in viral proteins spread to fixation by the end of the early chronic phase of infection in response to selection by CD8(+) T cells. Stochastic simulation was used to examine the effects of the transmission bottleneck and of potential interference among spreading immune-escape mutations on the adaptive dynamics of the virus in early infection. If major viral population genetic parameters are assigned realistic values that permit rapid adaptive evolution, then a bottleneck of a single genome is not inconsistent with the observed pattern of adaptive fixations. One requirement is strong selection by CD8(+) T cells that decreases over time. Such selection may reduce effective population sizes at linked loci through genetic hitchhiking. However, this effect is predicted to be minor in early infection because the transmission bottleneck reduces the effective population size to such an extent that the resulting strong selection and weak mutation cause beneficial mutations to fix sequentially and thus avoid interference.

Randomized controlled trial evaluating pictogram augmentation of HIV medication information.

BACKGROUND: Antiretroviral therapy for the management of HIV typically requires the chronic use of 3 or more medications. As such, patients with HIV are required to manage complex dosing schedules and are at risk of multiple potential adverse effects. The use of pictograms on medication vials as a means of improving patients' understanding of medication information has been shown to positively influence understanding and adherence compared to those using text alone. OBJECTIVE: To determine whether pictograms (Pharmaglyph) increase patient recall of targeted information associated with HIV medications and whether patients can interpret the intended meaning of pictograms that they had not seen previously. METHODS: A randomized, controlled trial was conducted in HIV-positive patients aged 19 years or older who were receiving a new prescription for an antiretroviral medication from the ambulatory pharmacy at St. Paul's Hospital in Vancouver, British Columbia, Canada. Participants were randomized to receive either pictogram-enhanced medication information or standard counseling. At the first follow-up visit, each patient's recall of the medication information was evaluated, and differences between groups were compared. RESULTS: Eighty-two subjects were randomized, 40 to the intervention group and 42 to the control arm. The mean (SD) number of HIV medications was nearly equal between the intervention and control groups: 3.0 (1.5) and 3.1 (1.4), respectively. After a mean of 34 days, 33 patients in the intervention arm and 39 in the control arm completed the study. The majority (88%) of the targeted pieces of information in the intervention group were correctly identified at follow-up, compared to only 2% in the control group (Fisher exact test; p < 0.0001). CONCLUSIONS: Pictograms improve the recall of targeted medication information among patients receiving antiretroviral therapy for HIV management; however, this appears to be dependent on the fact that these patients received a verbal explanation of each pictogram prior to use.

Fitness epistasis and constraints on adaptation in a human immunodeficiency virus type 1 protein region.

Fitness epistasis, the interaction among alleles at different loci in their effects on fitness, has potentially important consequences for adaptive evolution. We investigated fitness epistasis among amino acids of a functionally important region of the human immunodeficiency virus type 1 (HIV-1) exterior envelope glycoprotein (gp120). Seven mutations putatively involved in the adaptation of the second conserved to third variable protein region (C2-V3) to the use of an alternative host-cell chemokine coreceptor (CXCR4) for cell entry were engineered singly and in combinations on the wild-type genetic background and their effects on viral infectivity were measured. Epistasis was found to be common and complex, involving not only pairwise interactions, but also higher-order interactions. Interactions could also be surprisingly strong, changing fitness by more than 9 orders of magnitude, which is explained by some single mutations being practically lethal. A consequence of the observed epistasis is that many of the minimum-length mutational trajectories between the wild type and the mutant with highest fitness on cells expressing the alternative coreceptor are selectively inaccessible. These results may help explain the difficulty of evolving viruses that use the alternative coreceptor in culture and the delayed evolution of this phenotype in natural infection. Knowledge of common, complex, and strong fitness interactions among amino acids is necessary for a full understanding of protein evolution.

An adaptive walk by human immunodeficiency virus type 1 through a fluctuating fitness landscape.

The mutational landscape model of adaptive sequence evolution has been used to explain an unexpected strong positive linear relationship between marginal fitness and mean site-specific amino acid frequency in the functionally important HIV-1 gp120 V3 protein region. The model predicts a positive linear relationship between the probability that a particular beneficial allele, among several, is the next to spread to fixation during an adaptive walk, its transition probability, and the allele's selection coefficient. Here, stochastic simulation is used to confirm the intuition that the linear relationship between transition probabilities and selection coefficients, predicted by the model, should, under fluctuating selection, produce a linear relationship between allele frequency, averaged across populations, and fitness. In addition, these relationships hold for the effective population size and mutation rate of HIV-1 and for the moderately strong selection observed for V3. A survey of the strength of mutation for diverse organisms suggests that these relationships may be widely applicable.

Amino acid covariation in a functionally important human immunodeficiency virus type 1 protein region is associated with population subdivision.

The frequently reported amino acid covariation of the highly polymorphic human immunodeficiency virus type 1 (HIV-1) exterior envelope glycoprotein V3 region has been assumed to reflect fitness epistasis between residues. However, nonrandom association of amino acids, or linkage disequilibrium, has many possible causes, including population subdivision. If the amino acids at a set of sequence sites differ in frequencies between subpopulations, then analysis of the whole population may reveal linkage disequilibrium even if it does not exist in any subpopulation. HIV-1 has a complex population structure, and the effects of this structure on linkage disequilibrium were investigated by estimating within- and among-subpopulation components of variance in linkage disequilibrium. The amino acid covariation previously reported is explained by differences in amino acid frequencies among virus subpopulations in different patients and by nonsystematic disequilibrium among patients. Disequilibrium within patients appears to be entirely due to differences in amino acid frequencies among sampling time points and among chemokine coreceptor usage phenotypes of virus particles, but not source tissues. Positive selection explains differences in allele frequencies among time points and phenotypes, indicating that these differences are adaptive rather than due to genetic drift. However, the absence of a correlation between linkage disequilibrium and phenotype suggests that fitness epistasis is an unlikely cause of disequilibrium. Indeed, when population structure is removed by analyzing sequences from a single time point and phenotype, no disequilibrium is detectable within patients. These results caution against interpreting amino acid covariation and coevolution as evidence for fitness epistasis.

Divergent patterns of selection on the DAB and DXB MHC class II loci in Xiphophorus fishes.

Two MHC class II loci, DAB (a classical class II locus) and DXB (putatively a non-classical class II locus), were sequenced in samples of individuals from two populations of swordtail fish, Xiphophorus multilineatus and X. pygmaeus. The DAB locus showed higher levels of genetic variation in the B1-encoding region, (putative binding region) than the DXB locus. We used two methods to investigate d(N)/d(S) ratios. The results from a maximum likelihood method based on phylogenetic relationships indicated positive selection on the B1 region of DAB (this method could not be used on DXB). Results from a coalescent-based method also showed evidence for positive selection in the B1 region of DAB, but only weak evidence for selection on the DXB. Further analyses indicated that recombination is an important source of variation in the B1 region of DAB, but has a relatively small effect on DXB. Overall, our results were consistent with the hypothesis that the DAB locus is under positive selection driven by antagonistic coevolution, and that the DXB locus plays the role of a non-classical MHC II locus. We also used simulations to investigate the presence of an elevated synonymous substitution rate in the binding region. The simulations revealed that the elevated rate could be caused by an interaction between positive selection and codon bias.

Site-specific amino acid frequency, fitness and the mutational landscape model of adaptation in human immunodeficiency virus type 1.

Analysis of the intensely studied HIV-1 gp120 V3 protein region reveals that the among-population mean site-specific frequency of an amino acid is a measure of its relative marginal fitness. This surprising result may arise if populations are displaced from mutation-selection equilibrium by fluctuating selection and if the probability of fixation of a beneficial amino acid is proportional to its selection coefficient.