Biomedical subjects

Daniel E L Promislow

Publications and source records attributed to Daniel E L Promislow.

15 recordsLinked to original sources

PubMed2006

Are functional and demographic senescence genetically independent?

Biogerontology has traditionally focused on demographic senescence by searching for environmental manipulations and genes that extend life span. Relatively little is known about age-specific changes in functional traits and how demographic and functional senescence are genetically (co)regulated. To determine whether functional and demographic senescence have a similar genetic basis, we measured genotypic variation in the age-related change in cold-stress resilience and age-specific mortality using ten inbred lines of Drosophila melanogaster. Cold-stress resilience was measured as the average time for a population of flies to recover from a chill coma after being placed on melting ice for 6 h. We found genotypic variation in both sexes for chill-coma resilience, for the rate at which it declines with age, for longevity, for the initial mortality rate, and for the rate at which mortality increases with age. However, there was no genotypic correlation between any of these functional and demographic parameters. These results suggest that deterioration of at least some functional traits might be genetically independent of mortality patterns. Models for the genetic basis of senescence may do well to distinguish between quality and quantity of life in terms of their genetic architectures, and the way selection acts upon these two age-related factors.

Age Factors↗

PubMed2006

Functional and evolutionary inference in gene networks: does topology matter?

The relationship between the topology of a biological network and its functional or evolutionary properties has attracted much recent interest. It has been suggested that most, if not all, biological networks are 'scale free.' That is, their connections follow power-law distributions, such that there are very few nodes with very many connections and vice versa. The number of target genes of known transcriptional regulators in the yeast, Saccharomyces cerevisiae, appears to follow such a distribution, as do other networks, such as the yeast network of protein-protein interactions. These findings have inspired attempts to draw biological inferences from general properties associated with scale-free network topology. One often cited general property is that, when compromised, highly connected nodes will tend to have a larger effect on network function than sparsely connected nodes. For example, more highly connected proteins are more likely to be lethal when knocked out. However, the correlation between lethality and connectivity is relatively weak, and some highly connected proteins can be removed without noticeable phenotypic effect. Similarly, network topology only weakly predicts the response of gene expression to environmental perturbations. Evolutionary simulations of gene-regulatory networks, presented here, suggest that such weak or non-existent correlations are to be expected, and are likely not due to inadequacy of experimental data. We argue that 'top-down' inferences of biological properties based on simple measures of network topology are of limited utility, and we present simulation results suggesting that much more detailed information about a gene's location in a regulatory network, as well as dynamic gene-expression data, are needed to make more meaningful functional and evolutionary predictions. Specifically, we find in our simulations that: (1) the relationship between a gene's connectivity and its fitness effect upon knockout depends on its equilibrium expression level; (2) correlation between connectivity and genetic variation is virtually non-existent, yet upon independent evolution of networks with identical topologies, some nodes exhibit consistently low or high polymorphism; and (3) certain genes show low polymorphism yet high divergence among independent evolutionary runs. This latter pattern is generally taken as a signature of positive selection, but in our simulations its cause is often neutral coevolution of regulatory inputs to the same gene.

Algorithms↗

PubMed2005

Testing evolutionary theories of aging in wild populations.

Classic theories for the evolution of senescence predict that rates of aging should be highest in populations in which extrinsic mortality is high. This predication is called into question in new work by David Reznick and co-workers, who found that guppies Poecilia reticulata derived from natural populations with high levels of predation live the longest in the laboratory. This study illustrates that the effect of mortality on aging might depend on how we define aging, and on the particular cause of increased mortality.

Journal Article↗

PubMed2005

Network thinking in ecology and evolution.

Although pairwise interactions have always had a key role in ecology and evolutionary biology, the recent increase in the amount and availability of biological data has placed a new focus on the complex networks embedded in biological systems. The increased availability of computational tools to store and retrieve biological data has facilitated wide access to these data, not just by biologists but also by specialists from the social sciences, computer science, physics and mathematics. This fusion of interests has led to a burst of research on the properties and consequences of network structure in biological systems. Although traditional measures of network structure and function have started us off on the right foot, an important next step is to create biologically realistic models of network formation, evolution, and function. Here, we review recent applications of network thinking to the evolution of networks at the gene and protein level and to the dynamics and stability of communities. These studies have provided new insights into the organization and function of biological systems by applying existing techniques of network analysis. The current challenge is to recognize the commonalities in evolutionary and ecological applications of network thinking to create a predictive science of biological networks.

Journal Article↗

PubMed2005

Phylogenetic perspectives in the evolution of parental care in ray-finned fishes.

Among major vertebrate groups, ray-finned fishes (Actinopterygii) collectively display a nearly unrivaled diversity of parental care activities. This fact, coupled with a growing body of phylogenetic data for Actinopterygii, makes these fishes a logical model system for analyzing the evolutionary histories of alternative parental care modes and associated reproductive behaviors. From an extensive literature review, we constructed a supertree for ray-finned fishes and used its phylogenetic topology to investigate the evolution of several key reproductive states including type of parental care (maternal, paternal, or biparental), internal versus external fertilization, internal versus external gestation, nest construction behavior, and presence versus absence of sexual dichromatism (as an indicator of sexual selection). Using a comparative phylogenetic approach, we critically evaluate several hypotheses regarding evolutionary pathways toward parental care. Results from maximum parsimony reconstructions indicate that all forms of parental care, including paternal, biparental, and maternal (both external and internal to the female reproductive tract) have arisen repeatedly and independently during ray-finned fish evolution. The most common evolutionary transitions were from external fertilization directly to paternal care and from external fertilization to maternal care via the intermediate step of internal fertilization. We also used maximum likelihood phylogenetic methods to test for statistical correlations and contingencies in the evolution of pairs of reproductive traits. Sexual dichromatism and nest construction proved to be positively correlated with the evolution of male parental care in species with external fertilization. Sexual dichromatism was also positively correlated with female-internal fertilization and gestation. No clear indication emerged that female-only care or biparental care were evolutionary outgrowths of male-only care, or that biparental care has been a common evolutionary stepping stone between paternal and maternal care. Results are discussed in the context of prior thought about the evolution of alternative parental care modes in vertebrates.

Animals↗

PubMed2004

Sex-specific effects of interventions that extend fly life span.

Genetic and environmental interventions that extend life span are a current focus in research on the biology of aging. Most of this work has focused on differences among genotypes and species. A recent study on fruit flies shows that life span extension because of dietary restriction can be highly sex-specific. Here we review the literature on sex-specific effects of 56 genetic and 41 environmental interventions that extend life span in Drosophila melanogaster. We found that only one-sixth of the experiments provided statistical tests of differences in response between males and females, suggesting that sex-specific effects have been largely ignored. When measured, the life span extension was female-biased in 8 of 16 cases, male-biased in 5 of 16 cases, and not significantly different in only 3 of 16 cases. We discuss possible explanations for the sex-specific differences and suggest various ways in which we might test these hypotheses. We argue that understanding sex differences in the response to life span-extending manipulations should lead to new insights about the basic mechanisms that underlie the biology of aging in both sexes.

Animals↗

PubMed2004

Protein networks, pleiotropy and the evolution of senescence.

The number of interactions, or connectivity, among proteins in the yeast protein interaction network follows a power law. I compare patterns of connectivity for subsets of yeast proteins associated with senescence and with five other traits. I find that proteins associated with ageing have significantly higher connectivity than expected by chance, a pattern not seen for most other datasets. The pattern holds even when controlling for other factors also associated with connectivity, such as localization of protein expression within the cell. I suggest that these observations are consistent with the antagonistic pleiotropy theory for the evolution of senescence. In further support of this argument, I find that a protein's connectivity is positively correlated with the number of traits it influences or its degree of pleiotropy, and further show that the average degree of pleiotropy is greatest for proteins associated with senescence. I explain these results with a simple mathematical model combining assumptions of the antagonistic pleiotropy theory for the evolution of senescence with data on network topology. These findings integrate molecular and evolutionary models of senescence, and should aid in the search for new ageing genes.

Aging↗

PubMed2003

Female age and sperm competition: last-male precedence declines as female age increases.

Until very recently, most studies of sperm competition have focused on variation in male competitive ability. However, we now know that a number of reproductive traits, including oviposition rate, use of stored sperm and receptivity to mating, vary with female condition. Because females can play an active part in the movement of sperm within their reproductive tract, sperm competition may be influenced by female condition. Existing studies of sperm competition in fruitflies ignore the effects of female condition, using females that are 3-4 days old and in their reproductive prime. But condition will decline as a female senesces. Here, we examine the effect of female age on the outcome of sperm competition in three strains of the fruitfly, Drosophila melanogaster. Previous studies have shown that female age influences preference for mates and male ejaculation strategies. In this study, we find that when males are mated to females that are older than 17 days, last-male sperm precedence decreases significantly. These results could lead to a greater understanding of the physiological mechanisms that regulate the outcome of sperm competition.

Aging↗

PubMed2003

Testing an 'aging gene' in long-lived drosophila strains: increased longevity depends on sex and genetic background.

Molecular advances of the past decade have led to the discovery of a myriad of 'aging genes' (methuselah, Indy, InR, Chico, superoxide dismutase) that extend Drosophila lifespan by up to 85%. Despite this life extension, these mutants are no longer lived than at least some recently wild-caught strains. Typically, long-lived mutants are identified in relatively short-lived genetic backgrounds, and their effects are rarely tested in genetic backgrounds other than the one in which they were isolated or derived. However, the mutant's high-longevity phenotype may be dependent on interactions with alleles that are common in short-lived laboratory strains. Here we set out to determine whether one particular mutant could extend lifespan in long-lived genetic backgrounds in the fruit fly, Drosophila melanogaster. We measured longevity and resistance to thermal stress in flies that were transgenically altered to overexpress human superoxide dismutase (SOD) in the motorneurones in each of 10 genotypes. Each genotype carried the genetic background from a different naturally long-lived wild-caught Drosophila strain. While SOD increased lifespan on average, the effect was genotype- and sex-specific. Our results indicate that naturally segregating genes interact epistatically with the aging gene superoxide dismutase to modify its ability to extend longevity. This study points to the need to identify mutants that increase longevity not only in the lab strain of origin but also in naturally long-lived genetic backgrounds.

Aging↗

PubMed2002

Biologists finally horn in on senescence in the wild.

In 1995, biologists discovered an unusual new species, the antler fly (Protophila litigata). Antler flies inhabit discarded moose and deer antlers for most of their life cycle, and male antler flies exhibit sexually selected behaviors on their home antlers. It now turns out that these curious flies might provide new insights into the evolution of aging. For years, biologists assumed that senescence did not occur in the wild. But over the past decade, several studies of natural populations of birds and mammals have found age-related declines in rates of reproduction or survival, indicating senescence. A new study of antler flies by Bonduriansky and Brassil provides the first evidence for senescence in a wild invertebrate. The researchers are able to mark individual flies and follow them throughout their entire, albeit short, life-spans. This small species offers huge opportunities to study senescence and age-related selection on fitness characters in the wild.

Aging↗

PubMed2002

Genes, culture, and aging flies--what the lab can and cannot tell us about natural genetic variation for senescence.

Model organisms cultured in the lab provide a powerful way to explore basic biological processes. However, lab culture can select for high early fecundity and dramatically shorten the life-span of lab organisms. Studies that use these short-lived organisms to identify aging-related genes might identify genes that simply restore the organism's original life-span. These results might not be fully relevant to wild populations. Experiments that reduce selection for shorter life-span or seek genes in naturally long-lived cohorts should lead to a more accurate understanding of aging.

Aging↗

PubMed2002

Advice to an aging scientist.

Fifty years ago, Peter Medawar and George Williams developed two now-classic theories for the evolution of senescence. In the past 20 years, evolutionary biologists studying aging have developed explicit mathematical models of these theories, used these models to derive explicit predictions, and tested these predictions using a variety of approaches. But, we argue here, our singular focus on these models may have hindered progress in evolutionary studies of aging. Research in this area has not kept pace with dramatic advances in evolutionary theory and molecular genetics. Progress in evolutionary studies of aging will depend on a bold, integrative approach, incorporating evolutionary and molecular advances from other fields, along with the powerful statistical and mathematical tools now available. We discuss several specific examples where we may gain new insight into the causes of aging by looking to other evolutionary phenomena, including sexual conflict and the evolution of social behavior. In addition, we present new results which suggest that the analysis of gene networks may lend particular insight into the genetic underpinnings of the aging process.

Aging↗

PubMed2002

Age-specific metabolic rates and mortality rates in the genus Drosophila.

Early theories of aging suggested that organisms with relatively high metabolic rates would live shorter lives. Despite widespread tests of this 'rate of living' theory of aging, there is little empirical evidence to support the idea. A more fine-grained approach that examined age-related changes in metabolic rate over the life span could provide valuable insight into the relationship between metabolic rate and aging. Here we compare age-related metabolic rate (measured as CO2 production per hour) and age-related mortality rate among five species in the genus Drosophila. We find no evidence that longer-lived species have lower metabolic rates. In all five species, there is no clear evidence of an age-related metabolic decline. Metabolic rates are strikingly constant throughout the life course, with the exception of females of D. hydei, in which metabolic rates show an increase over the first third of the life span and then decline. We argue that some physiological traits may have been shaped by such strong selection over evolutionary time that they are relatively resistant to the decline in the force of selection that occurs within the life time of a single individual. We suggest that comparisons of specific traits that do not show signs of aging with those traits that do decline with age could provide insight into the aging process.

Aging↗

PubMed2002

Sperm competitive ability and genetic relatedness in Drosophila melanogaster: similarity breeds contempt.

Offspring of close relatives often suffer severe fitness consequences. Previous studies have demonstrated that females, when given a choice, will choose to avoid mating with closely related males. But where opportunities for mate choice are limited or kin recognition is absent, precopulatory mechanisms may not work. In this case, either sex could reduce the risks of inbreeding through mechanisms that occur during or after copulation. During mating, males or females could commit fewer gametes when mating with a close relative. After mating, females could offset the effects of mating with a closely related male through cryptic choice. Few prior studies of sperm competition have examined the effect of genetic similarity, however, and what studies do exist have yielded equivocal results. In an effort to resolve this issue, we measured the outcome of sperm competition when female Drosophila melanogaster were mated to males of four different degrees of genetic relatedness and then to a standardized competitor. We provide the strongest evidence to date that sperm competitive ability is negatively correlated with relatedness, even after controlling for inbreeding depression.

Animals↗

PubMed2002

The role of parental age effects on the evolution of aging.

Many studies have found that older parents have shorter-lived offspring. However, the evolutionary significance of these findings is poorly understood. We carried out large-scale demographic experiments to examine the direct effect of maternal age and paternal age on offspring aging in inbred and outbred strains of the fruit fly Drosophila melanogaster. We found that the age of mothers and, to a lesser extent, the age of fathers can have a large influence on both offspring longevity and the shape of the age-specific mortality trajectory. In two independent experiments we found that older mothers generally produced shorter-lived offspring, although the exact effect of maternal age on offspring longevity differed among strains. These results suggest that maternal age effects on progeny aging may influence the evolution of aging.

Aging↗