De Novo Mutation Rate Variation and Its Determinants in Chlamydomonas.

De novo mutations are central for evolution, since they provide the raw material for natural selection by regenerating genetic variation. However, studying de novo mutations is challenging and is generally restricted to model species, so we have a limited understanding of the evolution of the mutation rate and spectrum between closely related species. Here, we present a mutation accumulation (MA) experiment to study de novo mutation in the unicellular green alga Chlamydomonas incerta and perform comparative analyses with its closest known relative, Chlamydomonas reinhardtii.

Extensive de novo mutation rate variation between individuals and across the genome of Chlamydomonas reinhardtii.

Describing the process of spontaneous mutation is fundamental for understanding the genetic basis of disease, the threat posed by declining population size in conservation biology, and much of evolutionary biology. Directly studying spontaneous mutation has been difficult, however, because new mutations are rare. Mutation accumulation (MA) experiments overcome this by allowing mutations to build up over many generations in the near absence of natural selection.

Higher resources decrease fluctuating selection during host-parasite coevolution.

We still know very little about how the environment influences coevolutionary dynamics. Here, we investigated both theoretically and empirically how nutrient availability affects the relative extent of escalation of resistance and infectivity (arms race dynamic; ARD) and fluctuating selection (fluctuating selection dynamic; FSD) in experimentally coevolving populations of bacteria and viruses. By comparing interactions between clones of bacteria and viruses both within- and between-time points, we show that increasing nutrient availability resulted in coevolution shifting from FSD, with fluctuations in average infectivity and resistance ranges over time, to ARD.

Spontaneous mutation accumulation in multiple strains of the green alga, Chlamydomonas reinhardtii.

Estimates of mutational parameters, such as the average fitness effect of a new mutation and the rate at which new genetic variation for fitness is created by mutation, are important for the understanding of many biological processes. However, the causes of interspecific variation in mutational parameters and the extent to which they vary within species remain largely unknown. We maintained multiple strains of the unicellular eukaryote Chlamydomonas reinhardtii, for approximately 1000 generations under relaxed selection by transferring a single cell every ~10 generations.

Estimate of the spontaneous mutation rate in Chlamydomonas reinhardtii.

The nature of spontaneous mutations, including their rate, distribution across the genome, and fitness consequences, is of central importance to biology. However, the low rate of mutation has made it difficult to study spontaneous mutagenesis, and few studies have directly addressed these questions. Here, we present a direct estimate of the mutation rate and a description of the properties of new spontaneous mutations in the unicellular green alga Chlamydomonas reinhardtii.

Selection on non-social traits limits the invasion of social cheats.

While the conditions that favour the maintenance of cooperation have been extensively investigated, the significance of non-social selection pressures on social behaviours has received little attention. In the absence of non-social selection pressures, patches of cooperators are vulnerable to invasion by cheats. However, we show both theoretically, and experimentally with the bacterium Pseudomonas fluorescens, that cheats may be unable to invade patches of cooperators under strong non-social selection (both a novel abiotic environment and to a lesser extent, the presence of a virulent parasite).

Host-parasite coevolutionary arms races give way to fluctuating selection.

Host-parasite coevolution is a key driver of biological diversity and parasite virulence, but its effects depend on the nature of coevolutionary dynamics over time. We used phenotypic data from coevolving populations of the bacterium Pseudomonas fluorescens SBW25 and parasitic phage SBW25Φ2, and genetic data from the phage tail fibre gene (implicated in infectivity evolution) to show that arms race dynamics, typical of short-term studies, decelerate over time. We attribute this effect to increasing costs of generalism for phages and bacteria with increasing infectivity and resistance.

Comparative analysis of myxococcus predation on soil bacteria.

Predator-prey relationships among prokaryotes have received little attention but are likely to be important determinants of the composition, structure, and dynamics of microbial communities. Many species of the soil-dwelling myxobacteria are predators of other microbes, but their predation range is poorly characterized. To better understand the predatory capabilities of myxobacteria in nature, we analyzed the predation performance of numerous Myxococcus isolates across 12 diverse species of bacteria.

Impact of bacterial mutation rate on coevolutionary dynamics between bacteria and phages.

Mutator bacteria are frequently found in natural populations of bacteria and although coevolution with parasitic viruses (phages) is thought to be one reason for their persistence, it remains unclear how the presence of mutators affects coevolutionary dynamics. We hypothesized that phages must themselves adapt more rapidly or go extinct, in the face of rapidly evolving mutator bacteria. We compared the coevolutionary dynamics of wild-type Pseudomonas fluorescens SBW25 with a lytic phage to the dynamics of an isogenic mutator of P.

Selective breeding for differential saccharin intake as an animal model of drug abuse.

A positive relationship between the consumption of sweetened dietary substances (e.g. saccharin and sucrose) and drug abuse has been reported in both the human and other animal literature.

Higher locomotor response to cocaine in female (vs. male) rats selectively bred for high (HiS) and low (LoS) saccharin intake.

Rats selectively bred for high saccharin consumption (HiS) self-administer more oral ethanol and i.v. cocaine than those selectively bred for low saccharin consumption (LoS).

Impulsivity (delay discounting) for food and cocaine in male and female rats selectively bred for high and low saccharin intake.

Previous research in rats indicates that delay discounting for food, a model of impulsivity, predicted the rate of acquisition of cocaine self-administration. In other studies, rats bred for high saccharin intake (HiS) acquired cocaine self-administration at higher rates than those with low saccharin intake (LoS), and female (F) rats acquired cocaine self-administration more rapidly than males (M). The purpose of this study was to examine a possible connection between impulsivity, saccharin intake, and sex by comparing M and F rats from the HiS and LoS selectively bred lines on measures of impulsivity; i.

Experimental coevolution with bacteria and phage. The Pseudomonas fluorescens--Phi2 model system.

Parasites are ubiquitous in biological systems and antagonistic coevolution between hosts and parasites is thought be a major ecological and evolutionary force. Recent experiments using laboratory populations of bacteria and their parasitic viruses, phage, have provided the first direct empirical evidence of antagonistic coevolution in action. In this article we describe this model system and synthesise recent findings that address the causes and consequences of antagonistic coevolution.

Differential impact of simultaneous migration on coevolving hosts and parasites.

Background: The dynamics of antagonistic host-parasite coevolution are believed to be crucially dependent on the rate of migration between populations. We addressed how the rate of simultaneous migration of host and parasite affected resistance and infectivity evolution of coevolving meta-populations of the bacterium Pseudomonas fluorescens and a viral parasite (bacteriophage). The increase in genetic variation resulting from small amounts of migration is expected to increase rates of adaptation of both host and parasite.

Regulation of intravenous cocaine self-administration in rats selectively bred for high (HiS) and low (LoS) saccharin intake.

Rationale: Rats selectively bred for high saccharin (HiS) intake consume more alcohol and acquire intravenous (i.v.) cocaine self-administration more rapidly than their low saccharin (LoS)-consuming counterparts.

Escalation of i.v. cocaine self-administration and reinstatement of cocaine-seeking behavior in rats bred for high and low saccharin intake.

Rationale: Rats selectively bred for high saccharin (HiS) intake consume more alcohol, acquire intravenous (i.v.) cocaine self-administration more rapidly, and show more dysregulated patterns of cocaine self-administration than their low saccharin-consuming (LoS) counterparts.

Sex differences in physical dependence on orally self-administered phencyclidine (PCP) in rhesus monkeys (Macaca mulatta).

Withdrawal from orally self-administered phencyclidine (PCP) has been shown to alter operant baselines of food-maintained responding. The goal of the present study was to determine whether there are sex differences in these alterations. Seven female and 7 male rhesus monkeys (Macaca mulatta) were given concurrent access to PCP and water under fixed ratio (FR) 8 schedules during 2 daily sessions that alternated with 2 sessions during which pellet deliveries were contingent on lever presses under an FR 64 schedule.

The effect of migration on local adaptation in a coevolving host-parasite system.

Antagonistic coevolution between hosts and parasites in spatially structured populations can result in local adaptation of parasites; that is, the greater infectivity of local parasites than foreign parasites on local hosts. Such parasite specialization on local hosts has implications for human health and agriculture. By contrast with classic single-species population-genetic models, theory indicates that parasite migration between subpopulations might increase parasite local adaptation, as long as migration does not completely homogenize populations.

Sex differences in the escalation of oral phencyclidine (PCP) self-administration under FR and PR schedules in rhesus monkeys.

Rationale: Studies with male rats indicate that long access (LgA) vs short access (ShA) to i.v. cocaine and heroin self-administration leads to an escalation of drug intake and a subsequent upward shift of the dose-response function.

Escalation of intravenous cocaine self-administration, progressive-ratio performance, and reinstatement in rats selectively bred for high (HiS) and low (LoS) saccharin intake.

Rationale: Rats selectively bred for high saccharin (HiS) intake consume more alcohol and acquire intravenous (IV) cocaine self-administration more rapidly than their low saccharin (LoS) consuming counterparts.

Objectives: The purpose of the present study was to determine whether HiS and LoS rats also differ in the escalation, maintenance, and reinstatement of IV cocaine self-administration.

Methods: LoS and HiS female rats were allowed to self-administer cocaine [0.

Sex and estrogen influence drug abuse.

Evidence is accumulating that the etiology, epidemiology, consequences and mechanisms that underlie drug abuse are different in males and females. In this review, we present examples of sex differences in all phases of drug abuse, including acquisition, steady-state maintenance, escalation, dysregulation, withdrawal, relapse and treatment. Most reported findings are based on laboratory research in animals, but there are corroborating reports from human clinical and epidemiological studies.

Neuropharmacokinetic and dynamic studies of agmatine (decarboxylated arginine).

Agmatine has been previously proposed to represent a novel neurotransmitter. One of the criteria required to test that hypothesis is that the exogenously administered chemical produces pharmacological effects similar to the physiological effects of the putative neurotransmitter. Since agmatine was first identified in brain, approximately sixty studies of the in vivo effects of exogenously administered agmatine have been reported.

Decreased cocaine self-administration in Kir3 potassium channel subunit knockout mice.

Multiple G protein-linked neurotransmitter systems have been implicated in the behavioral effects of cocaine. While actions of certain neurotransmitter receptor subtypes and transporters have been identified, the role of individual G protein-regulated enzymes and ion channels in the effects of cocaine remains unclear. Here, we assessed the contribution of G protein-gated, inwardly rectifying potassium (Kir3/GIRK) channels to the locomotor-stimulatory and reinforcing effects of cocaine using knockout mice lacking one or both of the key neuronal channel subunits, Kir3.

Effects of agmatine on the escalation of intravenous cocaine and fentanyl self-administration in rats.

Escalation of drug intake reliably occurs when animals are allowed extended self-administration access. As a form of plasticity, escalation of drug intake may be accompanied by neuroadaptive changes that are related to the transition from controlled use to addiction. The purpose of the present experiment was to examine the effects of agmatine (decarboxylated L-arginine) on the escalation of intravenous (iv) fentanyl and cocaine self-administration in rats.

Intravenous cocaine and heroin self-administration in rats selectively bred for differential saccharin intake: phenotype and sex differences.

Rationale: Rats selectively bred for high intake of a sweet saccharin solution (HiS) consume more ethanol than their low-saccharin intake (LoS) counterparts. The HiS phenotype may be a predictor of abuse of other drugs via other routes of administration.

Objective: HiS and LoS, male and female rats were tested for acquisition of IV cocaine and heroin self-administration under a fixed-ratio 1 (FR1) schedule, and cocaine-reinforced behavior was examined under a progressive-ratio (PR) schedule.