Multiple Mating But Not Recombination Causes Quantitative Increase in Offspring Genetic Diversity for Varying Genetic Architectures

Explaining the evolution of sex and recombination is particularly intriguing for some species of eusocial insects because they display exceptionally high mating frequencies and genomic recombination rates. Explanations for both phenomena are based on the notion that both increase colony genetic diversity, with demonstrated benefits for colony disease resistance and division of labor. However, the relative contributions of mating number and recombination rate to colony genetic diversity have never been simultaneously assessed. Our study simulates colonies, assuming different mating numbers, recombination rates, and genetic architectures, to assess their worker genotypic diversity. The number of loci has a strong negative effect on genotypic diversity when the allelic effects are inversely scaled to locus number. In contrast, dominance, epistasis, lethal effects, or limiting the allelic diversity at each locus does not significantly affect the model outcomes. Mating number increases colony genotypic variance and lowers variation among colonies with quickly diminishing returns. Genomic recombination rate does not affect intra- and inter-colonial genotypic variance, regardless of mating frequency and genetic architecture. Recombination slightly increases the genotypic range of colonies and more strongly the number of workers with unique allele combinations across all loci. Overall, our study contradicts the argument that the exceptionally high recombination rates cause a quantitative increase in offspring genotypic diversity across one generation. Alternative explanations for the evolution of high recombination rates in social insects are therefore needed. Short-term benefits are central to most explanations of the evolution of multiple mating and high recombination rates in social insects but our results also apply to other species.     

棘胸蛙求偶鸣声与温度有关但与体大小无关

鸣声被认为是鉴别蛙类物种最有效的特征之一,但受许多因素影响。为了研究环境因素和身体大小与雄性棘胸蛙鸣声特征的关系,在人工仿生态养殖条件下测量环境温度和体温以及蛙体的大小(体重、体长),并通过个体定位,录制繁殖期中雄性棘胸蛙的求偶鸣声,分析鸣叫参数。结果表明,棘胸蛙雄性鸣声特征测量参数与体重、体长无相关性,而鸣声特征中的鸣叫时长、音节时长与环境温度、水温、体温、泄殖腔温度存在负相关性。研究结果提示在开展棘胸蛙鸣声学研究时应注意温度对其的影响。     

Evidence of Diversifying Selection in Human Papillomavirus Type 16 E6 But Not E7 Oncogenes

Human papillomavirus type 16 is a common sexually transmitted pathogen capable of giving rise to cervical intraepithelial neoplasia and invasive carcinoma through the expression and activity of two adjacent oncogenes: E6 and E7. Naturally occurring amino acid variation is commonly observed in the E6 protein but to a much lesser extent in E7. In order to investigate the evolutionary mechanisms involved in the generation and maintenance of this variation, we examine 42 distinct E6-E7 haplotypes using codon-based genealogical techniques. These techniques involve estimation of the ratio of nonsynonymous to synonymous substitutions (dn/ds) and allow testing for directional (positive) natural selection. Positive selection was detected for four codon sites within the E6 oncogene but not in any E7 codons. The amino acid compositions and locations of selected sites are described. Possible sources of natural selection including antiviral immune pressure and polymorphism of host cellular proteins are discussed.     

Evolution of X-Degenerate Y Chromosome Genes in Greater Apes: Conservation of Gene Content in Human and Gorilla,But Not Chimpanzee

Compared with the X chromosome, the mammalian Y chromosome is considerably diminished in size and has lost most of its ancestral genes during evolution. Interestingly, for the X-degenerate region on the Y chromosome, human has retained all 16 genes, while chimpanzee has lost 4 of the 16 genes since the divergence of the two species. To uncover the evolutionary forces governing ape Y chromosome degeneration, we determined the complete sequences of the coding exons and splice sites for 16 gorilla Y chromosome genes of the X-degenerate region. We discovered that all studied reading frames and splice sites were intact, and thus, this genomic region experienced no gene loss in the gorilla lineage. Higher nucleotide divergence was observed in the chimpanzee than the human lineage, particularly for genes with disruptive mutations, suggesting a lack of functional constraints for these genes in chimpanzee. Surprisingly, our results indicate that the human and gorilla orthologues of the genes disrupted in chimpanzee evolve under relaxed functional constraints and might not be essential. Taking mating patterns and effective population sizes of ape species into account, we conclude that genetic hitchhiking associated with positive selection due to sperm competition might explain the rapid decline in the Y chromosome gene number in chimpanzee. As we found no evidence of positive selection acting on the X-degenerate genes, such selection likely targets other genes on the chimpanzee Y chromosome. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Breeding Strategies in Females of the Parasitoid Wasp Spalangia endius: Effects of Mating Status and Size

Does the mating status or body size of a female parasitoid wasp affect her host size choice or propensity to burrow? In Spalangia endius, using smaller hosts appears to reduce a female's cost of parasitization but not her son's fitness. However, virgin females, which produce only sons, did not preferentially parasitize smaller hosts. Mated females also showed no host size preference. Mated females burrowed more than virgins in the presence of hosts, although not in their absence. Burrowing may reduce a mated female's harassment from males, and not burrowing may increase a virgin female's chance of mating because males avoid burrowing. Mating did not increase female longevity. Greater female size increased the offspring production of mated females burrowing for hosts but not in the absence of burrowing and not in virgin females. A female's size had no significant effect on whether her first drill attempt was on a large or a small host or on the duration of her successful drills.     

Changes in Ambient Temperature Trigger Yawning But Not Stretching in Rats

Yawning appears to be involved in arousal, state change, and activity across vertebrates. Recent research suggests that yawning may support effective changes in mental state or vigilance through cerebral cooling. To further investigate the relationship between yawning, state change, and thermoregulation, 12 Sprague–Dawley rats (Rattus norvegicus) were exposed to a total of 2 h of ambient temperature manipulation over a period of 48 h. Using a repeated measures design, each rat experienced a range of increasing (22°C → 32°C), decreasing (32°C → 22°C), and constant temperatures (22°C; 32°C). Yawning and locomotor activity occurred most frequently during initial changes in temperature, irrespective of direction, compared to more extended periods of temperature manipulation. The rate of yawning also diminished during constant high temperatures (32°C) compared to low temperatures (22°C). Unlike yawning, however, stretching was unaffected by ambient temperature variation. These findings are compared to recent work on budgerigars (Melopsittacus undulatus), and the ecological selective pressures for yawning in challenging thermal environments are discussed. The results support previous comparative research connecting yawning with arousal and state change, and contribute to refining the predictions of the thermoregulatory hypothesis across vertebrates.     

Selection for Mating Reluctance in Females of a Diploid Parthenogenetic Strain of DROSOPHILA MERCATORUM

A diploid parthenogenetic strain of Drosophila mercatorum was outcrossed to produce genetic variance among the impaternate female offspring. Selection experiments were carried out for reluctance of the parthenogenetic females to mate.After only two cycles of selection, a parthenogenetic strain which is significantly less receptive to males from three different bisexual strains was obtained. It was also found that there is some degree of sexual isolation among the three bisexual strains used. The results support the idea that selection can render a newly produced diploid parthenogenetic strain behaviorally different from its bisexual ancestor. This appears to provide a framework which can explain the natural coexistence of diploid bisexual and diploid parthenogenetic biotypes in some species of insects.     

Sphingosylphosphorylcholine in Niemann-Pick Disease Brain: Accumulation in Type A But Not in Type B

A study of brain lipids in patients with the sphingomyelinase-deficient types of Niemann-Pick disease demonstrated that abnormal accumulation of sphingomyelin occurs only in the brain of neuronopathic type A patients but not in the non-neuronopathic type B. Additional lipid abnormalities were present in the type A brain. In contrast, the brain lipid profile was normal in type B patients. Since lysosphingolipids have been implicated in the biochemical pathogenesis of other genetic lysosomal sphingolipidoses, the occurrence of Sphingosylphosphorylcholine (lysosphingomyelin) was specifically investigated in brain and extraneural tissues, using an HPLC method with fluorescent detection of orthophtalaldehyde derivatives. Levels close to or below the limit of detection (10 pmol/mg tissue protein) were observed in normal and pathological controls. A striking accumulation was observed in brain of two Niemann-Pick type A patients (830 and 430 pmol/mg protein in 27-and 16-month-old children with severe and milder neurological course, respectively), which was not present at the fetal stage of the disease. No significant increase was found in brain tissue from a 3.5 year-old type B patient. In liver and spleen, abnormally high Sphingosylphosphorylcholine levels were observed in both types of the disease, with indication of a progressive increase during development. This study establishes the integrity of brain tissue in Niemann-Pick disease type B and suggests that the lysocompound Sphingosylphosphorylcholine could play a role in the pathophysiology of brain dysfunction in the neuronopathic type A.     

Mating Tactics in Response to Costs Incurred by Mating with Multiple Males in Wild Female Japanese Macaques

We investigated the costs of mating with multiple males in terms of feeding time, traveling distances, sexual proceptivity, and male aggression, for wild female (Macaca fuscata yakui) on Yakushima Island, Japan. We analyzed all-day focal sampling data from 7 females during the mating season (Sept.-Nov. 1996). On days when estrous females copulated with multiple males, they decreased their feeding time to half that of anestrous days, traveled longer distances, showed more proceptive sexual behaviors and received more aggression from subordinate males than on days when they copulated with only the 1st-ranking male. On days when females copulated with only the 1st-ranking male, they showed no difference in feeding time with that of anestrous days, and expended less effort than the above mating pattern because of short traveling distances, diminished sexual proceptivity and a lower frequency of aggression received. The results suggest that the costs of estrous vary according to female sexual proceptivity and the number and social status of mating partners. Female Japanese macaques exhibit a mixed mating strategy over prolonged estrous periods, which may provide females with opportunities to maximize the benefits of copulating with multiple males and to minimize the costs of estrus by mating with only the 1st-ranking male. During an estrous cycle, females may be adjusting efforts for reproduction and survival; i.e., mating vs. feeding.     

Circadian Modulation of Acute Alcohol Sensitivity But Not Acute Tolerance in Drosophila

An increased understanding of the factors affecting behavioral and neurological responses to alcohol and alcohol physiology is necessary given the tremendous toll alcohol abuse and alcoholism exert on individuals and society. At the behavioral and molecular levels, the response to alcohol appears remarkably conserved from Drosophila to humans, suggesting that investigations across model species can provide insight into the identification of common modulatory factors. We investigated the interaction between the circadian clock and alcohol sensitivity, alcohol tolerance, and alcohol absorbance in Drosophila melanogaster. Using a loss-of-righting reflex (LoRR) assay, we found that flies exhibit a circadian rhythm in the LoRR, with the greatest sensitivity to alcohol occurring from mid to late night, corresponding to the flies' inactive phase. As predicted, a circadian rhythm in the LoRR was absent in circadian mutant flies and under conditions in which the circadian clock was nonfunctional. Circadian modulation of the response to alcohol was not due to circadian regulation of alcohol absorbance. Similar to other animals, Drosophila develop acute and chronic tolerance to alcohol upon repeat exposures. We found that the circadian clock did not modulate the development of acute alcohol tolerance measured as the difference in sensitivity to alcohol between naïve and pre-exposed flies. Thus, the circadian clock modulates some, but not all, of the behavioral responses to alcohol exposure, suggesting that specific mechanisms underlie the observed circadian modulation of LoRR rather than global cellular circadian regulation. This study provides valuable new insights in our understanding of the circadian modulation of alcohol-induced behaviors that ultimately could facilitate preventative measures in combating alcohol abuse and alcoholism. (Author correspondence: lyons@bio.fsu.edu)     

Bigger Is Not Always Better: Females Prefer Males of Mean Body Size in Philautus odontotarsus

Most species are believed to evolve larger body sizes over evolutionary time. Previous studies have suggested that sexual selection, through male-male competition and female choice, favors larger males. However, there is little evidence of selection against large size. The female serrate-legged small treefrogs (Philautus odontotarsus) must carry passive males from leks to breeding grounds over relatively long distances after amplexus to find a suitable place to lay eggs. The costs of large male size may therefore decrease mating success due to reduced agility and/or higher energy requirements. Thus, we hypothesized that selection would not favor larger males in P. odontotarsus. Females can assess male body size on the basis of the dominant frequency of male calls in frogs. To assess female P. odontotarsus preferences for a potential mate’s body size, male calls of high, average and low dominant frequency were played back to the females in phonotaxis experiments. Results showed that most females prefer the advertisement call with average dominant frequency. In addition, we compared the body mass distribution of amplectant males with that of single males in nature. The body masses of amplectant males are more narrowly distributed in the intermediate range than that of single males. The phonotaxis results and the data of actual female preferences in the field show that females strongly prefer potential mates of mean body sizes, consistent with the view that, in this species at least, larger males are not always perceived as better by females. In the present study, P. odontotarsus provides an example of an amphibian species in which large size does not have an advantage in mating success for males. Instead, our results provide evidences that stabilizing selection favors the optimal intermediate size of males.     

Epidermal Growth Factor Induces Internalization But Not Degradation of the Epidermal Growth Factor Receptor in a Human Breast Cancer Cell Line

Abstract

Metabolism of the epidermal growth factor (EGF) receptor was studied in the MDA-MB-231 human breast cancer cell line. As in normal fibroblasts the EGF receptor from MDA-MB-231 cells was synthesized from a M_r =160,000 precursor and tunicamycin treatment of cells resulted in accumulation of a M_r =130,000 polypeptide. Unlike normal fibroblasts in which a M_r =170,000 mature form of the EGF receptor was found, MDA-MB-231 cells contained a M_r =172,000 mature form. Addition of EGF to MDA-MB-231 cells led to rapid internalization of EGF receptors, however, internalization did not affect receptor half-life and receptors did not recycle to the cell surface. EGF receptors could be visualized by immunofluorescence and remained sequestered in intracellular membranous structures following internalization. EGF was degraded slowly by MDA-MB-231 cells relative to degradation of EGF by normal cells. A high endogenous level of in vivo phosphorylation of threonine 654 of the EGF receptor was found in MDA-MB-231 cells and treatment of cells with 12-0-tetradecanoyl-phorbol-13-acetate (TPA) further stimulated phosphorylation of this residue. EGF induced receptor internalization resulted in dephosphorylation of threonine 654. The significance of these unusual properties of EGF receptor metabolism in MDA-MB-231 cells is discussed.     

Replication-Defective Adenovirus Vectors with Multiple Deletions Do Not Induce Measurable Vector-Specific T Cells in Human Trials

The magnitude and character of adenovirus serotype 5 (Ad5)-specific T cells were determined in volunteers with and without preexisting neutralizing antibodies (NAs) to Ad5 who received replication-defective Ad5 (rAd5)-based human immunodeficiency virus vaccines. There was no correlation between T-cell responses and NAs to Ad5. There was no increase in magnitude or activation state of Ad5-specific CD4⁺ T cells at time points where antibodies to Ad5 and T-cell responses to the recombinant gene products could be measured. These data indicate that rAd5-based vaccines containing deletions in the E1, E3, and E4 regions do not induce appreciable expansion of vector-specific CD4⁺ T cells.Replication-defective adenoviruses (rAd) have been engineered to provide high levels of expression of foreign inserts with minimum expression of adenovirus proteins, making them excellent candidates for vaccine and gene therapy applications (3, 16). Despite promising immunogenicity, a prophylactic vaccine trial of a serotype 5 rAd (rAd5) vector expressing human immunodeficiency virus (HIV) Gag, Pol, and Nef genes (Step trial) was recently halted due to an increase in HIV infections among volunteers who had preexisting neutralizing antibodies (NAs) to Ad5 (7). This finding raises the possibility that the presence of Ad5-specific T-cell responses (specifically CD4⁺ T-cell responses) in subjects with preexisting Ad5 NAs could be boosted by rAd5 vaccines, thereby providing an expanded susceptible target cell population that could be more easily infected by HIV. If this mechanism were operative, it would have broad implications for the future use of rAd viruses, and indeed other virus vectors, as vaccines or therapeutic agents within HIV-susceptible populations (2, 12, 15). We therefore measured the frequency, magnitude, and activation status of rAd5-specific T cells in HIV-uninfected volunteers who had received rAd5-based HIV vaccines in the presence or absence of preexisting NAs to Ad5.We studied 31 volunteers enrolled in two NIAID Institutional Review Board-approved phase I clinical trials of rAd5-based HIV vaccines. VRC 006 was a dose escalation study evaluating a single inoculation of a rAd5 mixture expressing EnvA, EnvB, EnvC, and fusion protein Gag/PolB at 10⁹, 10¹⁰, and 10¹¹ total particle units (10). VRC 008 evaluated DNA priming by needle and syringe or Biojector, followed by rAd5 boosting. Both studies enrolled healthy, HIV-uninfected adults; used the same rAd5 products; and evaluated immunogenicity on the day of and 4 weeks after rAd5 immunization. Both of these trials involved rAd5 products that contained deletions in the E1, E3, and E4 regions (8, 10).NAs to Ad5 were determined for all volunteers as previously described (19). A 90% NA titer of 12 or more was considered positive and taken as evidence of preexisting humoral immunity to Ad5. Volunteers were chosen for assessment of Ad5-specific T-cell responses based upon the availability of peripheral blood mononuclear cell samples at key time points and the presence or absence of preexisting NAs to Ad5. Only volunteers who received the vaccine (not the placebo) were included. Table ​Table11 lists the volunteers who were tested for Ad5-specific T-cell responses and their NA titers to Ad5 before and after rAd5 vaccination. All volunteers, except for one (volunteer 12) who had a less-than-maximum NA titer to Ad5 before vaccination, had an increase in titer by 4 weeks after vaccination, indicating the successful “take” of the rAd5-based vaccine. There was no correlation between rAd5 dose and increase in Ad5 NA titer.

TABLE 1.

Ad5 serostatus before and after vaccination

Environmental Predictors of Geographic Variation in Human Mating Preferences

Sexual selection theory classically posits consistent and directional mate-preferences for male traits that provide benefits to females. However, flexible mate-choice tactics may persist within a species when males display multiple desirable features that confer different benefits to females under variable environmental conditions. Ecological factors such as population density, resource demand, and sex ratio can influence the value that female animals place on certain male characteristics across mating environments. In this study, I used human mate-preference data from `lonely hearts' advertisements in the newspapers of 23 cities in the USA to assess geographic differences in female preferences for male traits (e.g. physical attributes, resource-holding potential, emotional characteristics, personal interests) in relation to these ecological parameters. I found that females placed more emphasis on the resource-accruing ability of prospective mates in densely populated cities and cities having greater resource demands (higher cost of living). In contrast, women from densely populated or resource-demanding cities placed less emphasis on the emotional aspects or personal interests of males. Preferences for physical features were not environmentally linked, but instead were a function of the degree to which females advertised their own physical attractiveness. Collectively, these results suggest that certain mate-choice criteria employed by women are sensitive to variation in local environmental conditions and that variable levels of resource or mate availability may favor different mating tactics across human populations.     

Subcutaneous Bortezomib in Multiple Myeloma Patients Induces Similar Therapeutic Response Rates as Intravenous Application But It Does Not Reduce the Incidence of Peripheral Neuropathy

Objective

Subcutaneous (SC) application of bortezomib has been recently introduced as a new application route in multiple myeloma (MM) patients. We performed an analysis to compare the outcomes of bortezomib-based therapy in multiple myeloma (MM) patients treated using either intravenous (IV) or subcutaneous (SC) route of administration.

Patients and methods

During January 2012 through December 2013, we performed a retrospective analysis of 446 patients with MM treated with bortezomib-based regimens (either once weekly – 63% or twice weekly – 27%) in both, the first line setting, and in relapse, with separate analysis of patients undergoing autologous stem cell transplantation. We assessed the response rates and toxicity profiles in both, IV and SC route of bortezomib administration.

Results

The response rates in both IV and SC arm were similar with overall response rate 71.7% vs 70.7%, complete remissions in 13.9% vs 8.6%, very good partial remissions in 30.8% vs 34.5% and partial remissions in 27% vs 27.6%. The most frequent grade ≥3 toxicities were anemia, thrombocytopenia and neutropenia, with no significant differences between IV and SC group. There were no significant differences in the rate of peripheral neuropathy (PN). PN of any grade was present in 48% in the IV arm and in 41% in the SC arm. PN grade ≥2 was present in 20% vs 18% and PN grade ≥3 was present in 6% vs 4%.

Conclusions

We conclude that subcutaneous application of bortezomib has similar therapeutic outcomes and toxicity profile as intravenous route of application. In our cohort there was no difference in the incidence of PN, suggesting that PN is dose dependent and might be reduced by lower intensity schemes rather than by the route of administration.     

Sperm Storage and Use After Multiple Mating in Dinarmus basalis (Hymenoptera: Pteromalidae)

Multiple mating and its effects on the sex ratio in Dinarmus basalis (Hymenoptera: Chalcidoidea, Pteromalidae), an ectoparasitoid of Callosobruchus maculatus (Coleoptera: Bruchidae), were investigated under controlled conditions. Once-mated females suffer a sperm depletion about 21 days after mating and thereafter are constrained to produce only haploid males. On the other hand, three-times-mated females store more sperm in their spermathecae (335 vs 147) and produce daughters during the major part of their reproductive life. Consequently, once-mated females showed a male-biased life time sex ratio (mean = 0.31) as opposed to three-times-mated females (mean = 0.63). Females can copulate only at the beginning of their reproductive life, and multiple mating must occur before egg-laying activity. This behavioral strategy could be an avoidance of consanguinity in a promiscuous environment. This ectoparasitoid species reveals a reproductive strategy which promotes polyandry and a very high sperm efficiency.     

Honey Bee Queens Do Not Count Mates to Assess their Mating Success

The mating system of honey bees (genus Apis) is extremely polyandrous, where reproductive females (queens) typically mate with 12 or more males (drones) during their mating flight(s). The evolutionary implications for hyperpolyandry have been subject to considerable debate and empirical testing because of the need to understand the proximate mechanisms that drive such extreme mating behavior despite the potential costs. The ability of queens to gauge and adjust their reproductive success is therefore important for selection to act on queen mating number at both the evolutionary (colony-level) and proximate (individual-level) timescales. We observed the mating flight activities of 80 queens in their respective mating nucleus hives each with a modified entrance that restricts flight attempts. We also attached a small weight (0, 16, or 38 mg) onto each queen’s thorax as a means of imposing additional flight costs. We then compared queens that were restricted from taking multiple mating flights to those that started oviposition after a single flight for their mating numbers as quantified by microsatellite analyses of their respective worker offspring. We found that neither additional weight nor restricted mating attempts had any significant effect on the effective mating frequencies of the experimental queens during their single mating flight. This observation suggests that queens are not adjusting their nuptial flight activity according to their precise mating number during their flight. These findings provide insights into the proximate regulation of honey bee queen mating behavior and the fitness consequences of hyperpolyandry at the colony level.