The role of insulin-like growth factor-1 (IGF-1) in growth and reproduction in female brown house snakes (Lamprophis fuliginosus).

Insulin-like growth factor-1 (IGF-1) is a peptide hormone critically involved in the regulation of key life-history traits such as growth and reproduction. Its structure and function are well-characterized among diverse mammal, fish, and bird species; however, little is known regarding the activities of IGF-1 in non-avian reptiles, particularly snakes and lizards. Nevertheless, several unique characteristics of reptiles, such as high metabolic flexibility and remarkable diversity in life-history strategy, suggest that they are of great interest in the study of endocrinological mechanisms underlying the regulation and evolution of life-history traits. Here we test for a relationship between IGF-1 and individual feeding rate, growth rate and reproductive stage in lab-reared female offspring of wild-caught oviparous house snakes, Lamprophis fuliginosus. We confirm a positive correlation between IGF-1 and both feeding and growth rates in sexually immature snakes, similar to that reported in other taxa. We also show a family effect on IGF-1, suggesting that IGF-1 levels may be heritable in these snakes, and serve as an important target of selection to produce divergent life-history strategies. Furthermore, we provide evidence that suggests that IGF-1 may peak rapidly after first mating, and subsequently decline prior to egg-laying, a phenomenon not previously reported in other taxa. These findings suggest that further comparative study of IGF-1 in snakes may reveal both the extent to which IGF-1 function is conserved across major taxonomic groups, as well as novel and intriguing roles for IGF-1 in the regulation of reproductive activities.

The evolution of aging and age-related physical decline in mice selectively bred for high voluntary exercise.

We tested whether selective breeding for early-age high voluntary exercise behavior over 16 generations caused the evolution of lifelong exercise behavior, life expectancy, and age-specific mortality in house mice (Mus domesticus). Sixteenth-generation mice from four replicate selection lines and four replicate random-bred control lines were individually housed from weaning through death and divided between two activity treatments (either with or without running wheels). Thus, there were four treatment groups: selection versus control crossed with active versus sedentary. The effects of selective breeding on life expectancy and age-specific mortality differed between females and males. In females, sedentary selection mice had early and high initial adult mortality and thus the lowest increases in mortality with age. Active selection females had the lowest early adult mortality, had limited mortality during midlife, and exhibited rapid increases in mortality rates at the very end of life; thus, they had deferred senescence. Median life expectancy was greater for both groups of selection females than for the two complementary groups of control females. Like females, sedentary selection males had the highest early adult mortality, and slow but steadily increasing mortality over the entire lifetime. Unlike the active selection females, active control males had the lowest mortality across the lifespan (until the end of life). Interestingly, the males with the lowest median life expectancy were those in the active selection treatment group. In both sexes, running (km/week) decreased over the lifetime to very low and virtually equivalent levels at the end of life in control and selection mice. Overall, these results demonstrate an evolutionary cost of selective breeding for males, regardless of exercise level, but a benefit for females when they have an outlet for the up-selected behavior. We conclude that correlated evolution of senescence occurs in mice selectively bred for high voluntary wheel running; exercise per se is beneficial for control mice of both sexes, but the impact on the effect of selection depends on sex; and the behavioral effect of exercise selection at an early age declines throughout the life span, which demonstrates decreasing genetic correlations over age for the genes involved in increased exercise.

The evolution of gene expression in mouse hippocampus in response to selective breeding for increased locomotor activity.

The evolution of behavior has been notoriously difficult to study at the molecular level, but mouse genetic technology offers new promise. We applied selective breeding to increase voluntary wheel running in four replicate lines of Mus domesticus (S mice) while maintaining four additional lines through random breeding to serve as controls (C mice). The goal of the study was to identify the gene expression profile of the hippocampus that may have evolved to facilitate the increased voluntary running. The hippocampus was of interest because it is known to display marked physiological responses in association with wheel running itself. We used high-density oligonucleotide arrays representing 11,904 genes. To control for the confounding influence of physical activity itself on gene expression, animals were housed individually without access to running wheels, and were sampled during the day when they are normally inactive. Two-month-old female mice in estrus were used (n = 16 total; two per line; 8 S and 8 C). After correcting for an acceptable false discovery rate (10%), 30 genes, primarily involved in transcription and translation, significantly increased expression whereas 23 genes, distributed among many categories including immune function and neuronal signaling, decreased expression in S versus C mice. These changes were relatively small in magnitude relative to the changes in gene expression that occur in the hippocampus in response to wheel running itself. A priori tests of dopamine receptor expression levels demonstrated an increase of approximately 20% in the expression of D2 and D4 receptors. These results suggest that relatively small changes in the expression patterns of hippocampal genes underlie large changes in phenotypic response to selection, and that the genetic architecture of running motivation likely involves the dopaminergic system as well as CNS signaling machinery.

Lifelong voluntary exercise in the mouse prevents age-related alterations in gene expression in the heart.

We present the first quantitative gene expression analysis of cardiac aging under conditions of sedentary and active lifestyles using high-density oligonucleotide arrays representing 11,904 cDNAs and expressed sequence tags (ESTs). With these data, we test the hypothesis that exercise attenuates the gene expression changes that normally occur in the aging heart. Male mice (Mus domesticus) were sampled from the 16th generation of selective breeding for high voluntary exercise. For the selective breeding protocol, breeders were chosen based on the maximum number of wheel revolutions run on days 5 and 6 of a test at 8 wk of age. For the colony sampled herein, mice were housed individually over their entire lifetimes (from weaning) either with or without access to running wheels. The hearts of these two treatment groups (active and sedentary) were assayed at middle age (20 mo) and old age (33 mo). Genes significantly affected by age in the hearts of the sedentary population by at least a 50% expression change (n = 137) were distributed across several major categories, including inflammatory response, stress response, signal transduction, and energy metabolism. Genes significantly affected by age in the active population were fewer (n = 62). Of the 42 changes in gene expression that were common to both treatment groups, 32 (72%) displayed smaller fold changes as a result of exercise. Thus exercise offset many age-related gene expression changes observed in the hearts of the sedentary animals. These results suggest that adaptive physiological mechanisms that are induced by exercise can retard many effects of aging on heart muscle at the transcriptional level.

Open-field behavior of house mice selectively bred for high voluntary wheel-running.

Open-field behavioral assays are commonly used to test both locomotor activity and emotionality in rodents. We performed open-field tests on house mice (Mus domesticus) from four replicate lines genetically selected for high voluntary wheel-running for 22 generations and from four replicate random-bred control lines. Individual mice were recorded by video camera for 3 min in a 1-m2 open-field arena on 2 consecutive days. Mice from selected lines showed no statistical differences from control mice with respect to distance traveled, defecation, time spent in the interior, or average distance from the center of the arena during the trial. Thus, we found little evidence that open-field behavior, as traditionally defined, is genetically correlated with wheel-running behavior. This result is a useful converse test of classical studies that report no increased wheel-running in mice selected for increased open-field activity. However, mice from selected lines turned less in their travel paths than did control-line mice, and females from selected lines had slower travel times (longer latencies) to reach the wall. We discuss these results in the context of the historical open-field test and newly defined measures of open-field activity.

Evolutionary adaptation to temperature. VIII. Effects of temperature on growth rate in natural isolates of Escherichia coli and Salmonella enterica from different thermal environments.

Are enteric bacteria specifically adapted to the thermal environment of their hosts? In particular, do the optimal temperatures and thermal niches of the bacterial flora reflect seasonal, geographic, or phylogenetic differences in their hosts' temperatures? We examined these questions by measuring the relationship between the temperature-dependent growth rates of enteric bacteria in a free-living ectothermic host. We sampled two species of enteric bacteria (Escherichia coli and Salmonella enterica) from three natural populations of slider turtles (Trachemys scripta elegans) seasonally over two years. Despite pronounced differences in turtle body temperatures at different seasons and in different locations, we found no evidence that the thermal growth profiles of these bacteria mirrored this variation. Optimal temperatures and maximal growth rates in rich medium were nearly the same for both bacterial species (35-36 degrees C, 2.5 doublings per hour). The thermal niche (defined as the range of temperatures over which 75% of maximal growth rate occurred) was slightly higher for E. coli (28.5-41.0 degrees C) than for S. enterica (27.7-39.8 degrees C), but the niche breadth was about the same for both. We also measured the thermal dependence of growth rate in these same bacterial species isolated from mammalian hosts. Both bacterial species had temperatures of maximal growth and thermal niches that were about 2 degrees C higher than those of their respective conspecifics sampled from turtles; niche breadths were not different. These data suggest that these bacterial species are thermal generalists that do not track fine-scale changes in their thermal environments. Even major differences in body temperatures, as great as those between ectothermic and endothermic hosts, may result in the evolution of rather modest changes in thermal properties.

Experimental evidence for the adaptive evolution of growth rate in the garter snake Thamnophis elegans.

The western terrestrial garter snake (Thamnophis elegans) varies significantly in individual growth rates and life-history traits (maturation, reproduction, and survival) among adjacent populations in nature. This study focuses on assessing the genetic and environmental components of the substantial among-population variation in growth rates. Litters of neonates from nine populations inhabiting either mountain meadow or lakeshore habitat were reared for one year in a common-garden experiment with two temperature treatments. Diet, frequency of feeding, light exposure, and daytime temperatures were identical for all individuals. The two different nighttime temperatures (20 degrees C and 25 degrees C) were chosen to mirror field differences in nighttime thermoregulatory constraints for mountain-meadow and lakeshore snakes, respectively. Temperature and source habitat interacted to affect first-year growth rate. Neonates from meadow dams grew fastest in the cooler treatment, whereas those from lakeshore dams grew fastest in the warmer treatment. The observation that naive neonates, which were gestated and raised under identical conditions, grew fastest in environments characteristic of their natal population is evidence both that there are genetic differences among populations for growth and that these differences reflect adaptation to local habitats at a very small geographic scale. In addition, significant directional selection for large birthweight was measured for neonates from all populations. These results are considered in the context of population colonization history, migration and selection, and competing models for growth rate variation.