Comparison of insect kinin analogs with cis-peptide bond motif 4-aminopyroglutamate identifies optimal stereochemistry for diuretic activity

The insect kinins are present in a wide variety of insects and function as potent diuretic peptides, though they are subject to rapid degradation by internal peptidases. Insect kinin analogs incorporating stereochemical variants of (2S,4S)-4-aminopyroglutamate (APy), a cis-peptide bond motif, demonstrate significant activity in a cricket diuretic assay. Insect kinin analogs containing (2R,4R)-APy, (2S,4R)-APy and (2S,4S)-APy are essentially equipotent on an insect diuretic assay, with EC(50) values of about 10(-7)M, whereas the (2R,4S)-APy analog is at least 10-fold more potent (EC(50) = 7 x 10(-9)M). Conformational studies in aqueous solution indicate that the (2R,4S)-APy analog is considerably more flexible than the other three variants, which may explain its greater potency. The work identifies the optimal stereochemistry for the APy scaffold with which to design biostable, peptidomimetic analogs with the potential to disrupt critical insect kinin-regulated processes in insects.     

Beta-amino acid analogs of an insect neuropeptide feature potent bioactivity and resistance to peptidase hydrolysis

Insect neuropeptides of the insect kinin class share a common C-terminal pentapeptide sequence F(1)X(1)(2)X(2)(3)W(4)G(5)-NH(2) (X(2)(3) = P, S, A) and regulate such critical physiological processes as water balance and digestive enzyme release. Analogs of the insect kinin class, in which the critical residues of F(1), P(3), and W(4) were replaced with beta(3)-amino acid or their beta(2)-homo-amino acid variants, have been synthesized by the solid phase peptide strategy. The resulting single- and double-replacement analogs were evaluated in an insect diuretic assay and enzyme digestion trials. Analogs modified in the core P(3) position produce a potent and efficacious diuretic response that is not significantly different from that obtained with the endogenous achetakinin peptides. The analogs also demonstrate enhanced resistance to hydrolysis by ACE and NEP, endopeptidases that inactivate the natural insect neuropeptides. This paper describes the first instance of beta-amino acids analogs of an arthropod peptide that demonstrate significant bioactivity and resistance to peptidase degradation.     

The genetics of adaptive coat color in gophers: coding variation at Mc1r is not responsible for dorsal color differences

The genetics of adaptation is a key problem in evolutionary biology. Pocket gophers of the species Thomomys bottae provide one of the most striking examples of coat color variation in mammals. Dorsal pelage color is strongly correlated with soil color across the range of the species, presumably reflecting the selective pressure exerted by predation. To investigate the genetic basis of coat color variation in T. bottae, we cloned and sequenced the melanocortin-1 receptor locus (Mc1r), a candidate pigmentation gene, in 5 dark and 5 light populations of the species. Our results show that, in contrast to many other species of mammals and other vertebrates, coding variation at Mc1r is not the main determinant of coat color variation in T. bottae. These results demonstrate that similar phenotypic variation may have a different genetic basis among different mammalian species.     

Factors Affecting Engorgement Behavior in the Salt Marsh Horse Fly, <Emphasis Type="Italic">Tabanus nigrovittatus</Emphasis> Macquart (Diptera: Tabanidae)

Female Tabanus nigrovittatus were field collected and used in laboratory experimentation to explore physiological and behavioral factors that affect engorgement. Previous studies showed sulfakinins act as feeding satiety factors in insects. This study demonstrates that sulfakinins have differing effects on engorgement that is dependent on the feeding technique used in the laboratory. The satiety effect of sulfakinin on flies engorging using the blood-soaked Kimwipe® feeding technique is not in agreement with previous experiments using an alternate feeding technique with artificial membranes. This study is the first to demonstrate that the temperature of blood is a significant factor for engorgement in this species. Also, the percentage of flies engorging is significantly different depending on the feeding technique used.     

A comparative study of development and demographic parameters of <Emphasis Type="Italic">Tetranychus merganser</Emphasis> and <Emphasis Type="Italic">Tetranychus kanzawai</Emphasis> (Acari: Tetranychidae) at different temperatures

We investigated the effect of temperature on development and demographic parameters such as the intrinsic rate of natural increase (r _m) of the two spider mite species Tetranychus merganser Boudreaux and T. kanzawai Kishida at eleven constant temperatures ranging from 15 to 40°C at intervals of 2.5°C. Both male and female T. merganser and T. kanzawai completed development from egg to adult at temperatures ranging from 15 to 37.5°C. The longest developmental duration of immature stages was found at 15°C and the shortest developmental duration was found at 35°C for both species. Using linear and non-linear developmental rate models, the lower thermal thresholds for egg-to-adult (female and male) and egg-to-egg development were estimated as 12.2–12.3°C for T. merganser and as 10.8°C for T. kanzawai. The highest developmental rates were observed at around 35°C, whereas the upper developmental thresholds were around 40°C for both species. In fact, at 40°C, a few eggs of either species hatched, but no larvae reached the next stage. The r _m-values of T. merganser ranged from 0.072 (15°C) to 0.411 day⁻¹ (35°C), whereas those of T. kanzawai ranged from 0.104 (15°C) to 0.399 (30°C). The r _m-values were higher for T. kanzawai than for T. merganser at temperatures from 15 to 30°C, but not at 35°C (0.348 day⁻¹). Total fecundity of T. merganser was also higher than that of T. kanzawai at 35°C. These results indicate that higher temperatures favor T. merganser more than T. kanzawai.     

Adaptive introgression of anticoagulant rodent poison resistance by hybridization between old world mice

Polymorphisms in the vitamin K 2,3-epoxide reductase subcomponent 1 (vkorc1) of house mice (Mus musculus domesticus) can cause resistance to anticoagulant rodenticides such as warfarin [1-3]. Here we show that resistant house mice can also originate from selection on vkorc1 polymorphisms acquired from the Algerian mouse (M. spretus) through introgressive hybridization. We report on a polymorphic introgressed genomic region in European M. m. domesticus that stems from M. spretus, spans >10 Mb on chromosome 7, and includes the molecular target of anticoagulants vkorc1 [1-4]. We show that in the laboratory, the homozygous complete vkorc1 allele of M. spretus confers resistance when introgressed into M. m. domesticus. Consistent with selection on the introgressed allele after the introduction of rodenticides in the 1950s, we found signatures of selection in patterns of variation in M. m. domesticus. Furthermore, we detected adaptive protein evolution of vkorc1 in M. spretus (Ka/Ks = 1.54-1.93) resulting in radical amino acid substitutions that apparently cause anticoagulant tolerance in M. spretus as a pleiotropic effect. Thus, positive selection produced an adaptive, divergent, and pleiotropic vkorc1 allele in the donor species, M. spretus, which crossed a species barrier and produced an adaptive polymorphic trait in the recipient species, M. m. domesticus.     

Variation in recombination rate across the genome: evidence and implications

Recent data from humans and other species provide convincing evidence of variation in recombination rate in different genomic regions. Comparison of physical and genetic maps reveals variation on a scale of megabases, with substantial differences between sexes. Recombination is often suppressed near centromeres and elevated near telomeres, but neither of these observations is true for all chromosomes. In humans, patterns of linkage disequilibrium and experimental measures of recombination from sperm-typing reveal dramatic hotspots of recombination on a scale of kilobases. Genome-wide variation in the amount of crossing-over may be due to variation in the density of hotspots, the intensity of hotspots, or both. Theoretical models of selection and linkage predict that genetic variation will be reduced in regions of low recombination, and this prediction is supported by data from several species. Heterogeneity in rates of crossing-over provides both an opportunity and a challenge for identifying disease genes: as associations occur in blocks, genomic regions containing disease loci may be identified with relatively few markers, yet identifying the causal mutations is unlikely to be achieved through associations alone.     

Interactions in a tritrophic acarine predator-prey metapopulation system IV: effects of host plant condition on Tetranychus urticae (Acari: Tetranychidae)

Feeding by spider mites can cause severe injury to a host plant and lead to a decreasing per capita growth rate and an increasing per capita emigration rate. Such density-dependent responses to local conditions are important in a metapopulation context because they allow the herbivores to colonize new host plants and thereby prolong the time until regional (metapopulation) extinction. In order to include density-dependent responses of the two-spotted spider mite (Tetranychus urticae) in a realistic metapopulation model, a series of greenhouse experiments was conducted with the purpose to quantify how the condition of bean plants (Phaseolus vulgaris) influences the demographic parameters of T. urticae. Plant age per se reduced the growth rate of the spider mites only slightly, whereas the growth rate declined significantly as the plants were injured by the mites. The relationships between plant condition (expressed by the plant injury index D) and the birth and loss (death + emigration) rates of the mites were quantified so as to predict population growth as a function of D. Maximum per capita growth rate (r) was estimated to be c. 0.21 day⁻¹. The growth rate is expected to be negative when D exceeds 0.8. When mites were allowed to emigrate to neighbouring plants via bridges, the per capita emigration rate increased almost exponentially with D. The proportion of eggs in the population decreased with D while the numerical ratio between immatures to adults and the sex ratio did not change with D. Overall, immatures and adults constituted 74% and 26%, respectively, of the active mites and c. 46% of the adults were males. The bridges that connected a donor plant with the surrounding recipient plants were responsible for the majority of the emigrations from donor plants. Most mites stopped after having crossed a single bridge, but a few crossed two bridges while none crossed three bridges within 24 h. The significance of the results for biological control is discussed. This revised version was published online in July 2006 with corrections to the Cover Date.