Hepatitis C Virus Variants with Decreased Sensitivity to Direct-Acting Antivirals (DAAs) Were Rarely Observed in DAA-Naive Patients prior to Treatment

The prevalence of naturally occurring hepatitis C virus (HCV) variants that are less sensitive to direct-acting antiviral (DAA) inhibitors has not been fully characterized. We used population sequence analysis to assess the frequency of such variants in plasma samples from 3,447 DAA-naive patients with genotype 1 HCV. In general, HCV variants with lower-level resistance (3- to 25-fold increased 50% inhibitor concentration [IC₅₀]) to telaprevir were observed as the dominant species in 0 to 3% of patients, depending on the specific variant, whereas higher-level resistant variants (>25-fold-increased IC₅₀) were not observed. Specific variants resistant to NS5A inhibitors were predominant in up to 6% of patients. Most variants resistant to nucleo(s/t)ide active-site NS5B polymerase inhibitors were not observed, whereas variants resistant to non-nucleoside allosteric inhibitors were observed in up to 18% of patients. The presence of DAA-resistant variants in NS5A, NS5B, or NS3 (including telaprevir-resistant variants), in baseline samples of treatment-naive patients receiving a telaprevir-based regimen in phase 3 studies did not affect the sustained viral response (SVR). Treatment-naive patients with viral populations containing the telaprevir-resistant variants NS3 V36M, T54S, or R155K at baseline achieved a 74% SVR rate, whereas patients with no resistant variants detected prior to treatment achieved a 76% SVR rate. The effect of specific resistant variant frequency on response to various DAA treatments in different patient populations, including interferon nonresponders, should be further studied.     

Sex ratio rather than population size affects genetic diversity in Antennaria dioica

• Habitat fragmentation and small population size can lead to genetic erosion in threatened plant populations. Classical theory implies that dioecy can counteract genetic erosion as it decreases the magnitude of inbreeding and genetic drift due to obligate outcrossing. However, in small populations, sex ratios may be strongly male‐ or female‐biased, leading to substantial reductions in effective population size. This may theoretically result in a unimodal relationship between sex ratios and genetic diversity; yet, empirical studies on this relationship are scarce.
• Using AFLP markers, we studied genetic diversity, structure and differentiation in 14 highly fragmented Antennaria dioica populations from the Central European lowlands. Our analyses focused on the relationship between sex ratio, population size and genetic diversity.
• Although most populations were small (mean: 35.5 patches), genetic diversity was moderately high. We found evidence for isolation‐by‐distance, but overall differentiation of the populations was rather weak. Females dominated 11 populations, which overall resulted in a slightly female‐biased sex ratio (61.5%). There was no significant relationship between population size and genetic diversity. The proportion of females was not unimodally but positively linearly related to genetic diversity.
• The high genetic diversity and low genetic differentiation suggest that A. dioica has been widely distributed in the Central European lowlands in the past, while fragmentation occurred only in the last decades. Sex ratio has more immediate consequences on genetic diversity than population size. An increasing proportion of females can increase genetic diversity in dioecious plants, probably due to a higher amount of sexual reproduction.

     

Short‐term temporal instability in fine‐scale genetic structure of masu salmon

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Genetic structure and gene flow among European corn borer populations from the Great Plains to the Appalachians of North America

• 1 Earlier population genetic spatial analysis of European corn borer Ostrinia nubilalis (Hübner) indicated no genetic differentiation even between locations separated by 720 km. This result suggests either high dispersal resulting in high gene flow or that populations are not in migration–drift equilibrium subsequent to their invasion of the central U.S.A. in the 1940s.
• 2 To discriminate among these two possibilities, samples were collected at 12 locations in eight states from New York to Colorado, a geographic scale that is three‐fold greater than previously tested. Eight microsatellite markers were employed to estimate genetic differentiation and gene flow among these populations, and to test for isolation‐by‐distance.
• 3 Although pairwise F_ST estimates were very low, there was a significant isolation‐by‐distance relationship.
• 4 Wright's neighbourhood area (i.e. the surface area covered by a panmictic group of individuals within a larger continuous distribution) was calculated as 433 km², and the radius indicates that approximately 13% of O. nubilalis adults disperse a net distance >12 km per generation from their natal source.
• 5 Analyses indicated significant differentiation between the north‐eastern region (New York and Pennsylvania) and the region combining sample locations from Ohio to Colorado, suggesting the potential for isolation of populations by topographic barriers in the Northeast.
• 6 Taken together, the results suggest that O. nubilalis exhibits substantial gene flow over long distances and that the lack of genetic differentiation between populations across hundreds of kilometres is not simply a result of migration–drift disequilibrium arising from the recent range expansion.

     

Sex-specific Activity Patterns in Periplaneta americana and their Relation to Mate-finding

The comparison of local song variations between a migratory and a sedentary population of starlings shows the species-specificity of the basic categories and of their variation range. Local variations were studied for different themes in the repertoire, near Kaiserslautern (West Germany) during the reproductive season of 1982. Results were compared with those previously obtained in Brittany (France). In the study area in Germany, 80 % of the individuals migrate in autumn whereas the Breton starlings remain near the colony all year. To compare the whistles of individuals of different regions, by examing the important variations in their frequency modulation, it is necessary to know the general basic features of the whistles. Using sonograms, the whistles of starlings can be divided into 8 general classes according to particular criteria: rhythmicity, modulation etc. Five themes, among these 8 classes, are sung by all or most of the individuals (“specific themes”). The analyses of whistles give us the following results:

• 1 The songs of the migratory population studied in W. Germany contain basic features corresponding to those known in the sedentary French population.
• 2 Like the Breton starlings, those in Germany show a “theme-specific” dialect distribution: the rhythmic theme shows several variants in an area of a few km², whereas the uniform simple theme presents only one variant over several 100 km². For the five themes, the dialectal mosaic is totally different: two birds can have the same variant of one given theme and sing different dialects of another.
• 3 The themes which, in France, show a great number of variants over a small area present the same tendency towards strong subdivision in dialects in Germany. In the two study areas, no correlation could be found between dialectal boundaries and ecological factors.
• 4 Considering that two starling populations with very different characteristics show such similarities in their basic song structures and also in their pattern of local variation (in the parameters concerned and in the sizes of the dialect areas) we may suppose that the basic structure of the specific themes could be determined by a genetic program. Some characteristics, like the precise details of the frequency modulation, may be due more to learning and may conform to the local dialect.

     

Aspects of interspecific interaction betweenReithrodontomys megalotis andMicrotus montanus in one acre enclosures

1. Two one acre enclosures were cleared of all resident rodents, and then, one enclosure was seeded with founder populations of Reithrodontomys megalotis (grid M) and the other with Reithrodontomys megalotis plus Microtus montanus (grid I). Founder populations consisted of eight animals for each species introduced and a sex ratio of 1∶1.
2. Five parameters were measured for a period of one year. Data collection was started in September 1971, and ended in September 1972; enumeration was conducted twice a month for three days.
3. The five parameters measured were: (1) population density through time and individual growth rates; (2) reproduction; (3) survival of age and sex classes; (4) sex ratio; and (5) sizes of home ranges.
4. There were no significant differences in three out of the five parameters studied. Density estimates along with individual growth rates were not significantly different between the grids. Reproduction, including breeding season and efficiency of reproductive effort, showed no or very little variation due to interspecific interaction. Home range sizes did not appear to be significantly different between the grids. Survival of juvenile males on grid I seemed lower and juvenile males from grid I were significantly smaller although possibly younger than those of grid M. The sex ratio of grid I was significantly different from the expected 1∶1 ratio.
5. It is postulated that Reithrodontomys megalotis may regulate their density by alteration of their sex ratios.

     

Identification of POMC Exonic Variants Associated with Substance Dependence and Body Mass Index

Background

Risk of substance dependence (SD) and obesity has been linked to the function of melanocortin peptides encoded by the proopiomelanocortin gene (POMC).

Methods and Results

POMC exons were Sanger sequenced in 280 African Americans (AAs) and 308 European Americans (EAs). Among them, 311 (167 AAs and 114 EAs) were affected with substance (alcohol, cocaine, opioid and/or marijuana) dependence and 277 (113 AAs and164 EAs) were screened controls. We identified 23 variants, including two common polymorphisms (rs10654394 and rs1042571) and 21 rare variants; 12 of which were novel. We used logistic regression to analyze the association between the two common variants and SD or body mass index (BMI), with sex, age, and ancestry proportion as covariates. The common variant rs1042571 in the 3′UTR was significantly associated with BMI in EAs (Overweight: P _adj = 0.005; Obese: P _adj = 0.018; Overweight+Obese: P _adj = 0.002) but not in AAs. The common variant, rs10654394, was not associated with BMI and neither common variant was associated with SD in either population. To evaluate the association between the rare variants and SD or BMI, we collapsed rare variants and tested their prevalence using Fisher’s exact test. In AAs, rare variants were nominally associated with SD overall and with specific SD traits (SD: P _FET,1df = 0.026; alcohol dependence: P _FET,1df = 0.027; cocaine dependence: P _FET,1df = 0.007; marijuana dependence: P _FET,1df = 0.050) (the P-value from cocaine dependence analysis survived Bonferroni correction). There was no such effect in EAs. Although the frequency of the rare variants did not differ significantly between the normal-weight group and the overweight or obese group in either population, certain rare exonic variants occurred only in overweight or obese subjects without SD.

Conclusion

These findings suggest that POMC exonic variants may influence risk for both SD and elevated BMI, in a population-specific manner. However, common and rare variants in this gene may exert different effects on these two phenotypes.     

A study of non-metric (qualitative) variation in Gujarati crania

Three hundred and seventy adult skulls (284 crania of unknown sex, 58 males and 28 females) from Gujarat State of India were examined for the incidence of non-metric variants and compared with other populations to establish the distance between them. In general the Gujarati incidences are of similar order to those in other series. The mean measures of divergence between Gujarati and other populations were all statistically significant (P less than 0.001). The Gujarati differed most from Australian Aborigines, but only slightly from the Burma, Punjab and Egypt samples. From the same material side and sex dimorphism was also tested to ascertain that how far sides and sexes can be pooled in Indian sample for making comparison between populations. In Gujarati population out of 22 cranial variants only four show sex difference and in case of bilateral traits, none of the variant has shown significant (P less than 0.05) side to side difference.     

Dental anomalies in the Japanese mole <Emphasis Type="Italic">Mogera wogura</Emphasis> from northeast China and the Primorsky region of Russia

Dental anomalies in the Japanese mole, Mogera wogura Temminck, 1842, from northeast China and the Primorsky region of Russia were examined based on 241 specimens. The most frequent dental anomaly was oligodonty, i.e., missing P² (18 cases) or P₃ (one case). Supernumerary teeth were observed in three cases, two of which were characterized by abnormal shapes. Morphological abnormalities in teeth (six cases) and an asymmetrically curved rostrum (one case) were also observed. Dental anomalies were found at higher frequencies in populations near the northern range limit of the species. This was not caused by size effects. We suggest that the high incidence of dental anomalies was the result of genetic drift, which increases in marginal populations. Considering the nature of subterranean mammals, our results suggest that the high frequency of dental anomalies in a marginal population could have initiated the evolution of dental formulae if parapatric or peripatric speciation occurs in such populations.     

Growth characteristics of freshwater pearl mussels,Margaritifera margaritifera (L.)

• 1 Shell growth in the freshwater pearl mussel, Margaritifera margaritifera, was investigated. Three non‐linear growth models (i.e. power, logistic and von Bertalanffy) were fitted to Scottish length‐at‐age data sets and compared.
• 2 Overall, the von Bertalanffy model outperformed the other two approaches, generating the smallest residuals in eight out of 11 samples (the logistic model provided slightly better fits to the other three). It was concluded that individual M. margaritifera appear to grow in an approximately asymptotic fashion and that the von Bertalanffy equation is an appropriate growth model to fit to freshwater pearl mussel length‐at‐age data.
• 3 The ranges in von Bertalanffy parameter estimates observed (k = 0.023–0.075 year^‐1, L_∞ = 77–158 mm, t_o = ‐3.93–4.33 years) are typical of those reported in northern European populations.
• 4 Most of the populations investigated had relatively low k‐values and high maximum age (A_max) estimates. This feature, which suggests high long‐term productivity and less vulnerability to decline (i.e. larger, longer‐living mussels produce more offspring), may be a reason why these populations have survived until now. The population which appears to be the most vulnerable (i.e. which has the highest k and lowest A_max) is probably not recruiting adequately at present.
• 5 An index of absolute growth (mean shell length‐at‐age) was also used for comparing different populations. Observed between‐ and within‐river differences in mussel growth patterns may be associated with a number of environmental factors, particularly water temperature and productivity.
• 6 A significant positive relationship between river length and mean mussel length‐at‐age was observed. In general, mussels grow large in large, cold rivers and vice versa, although there are exceptions which suggest that additional factors may be involved.

     

Individual growth rates do not predict aphid population densities under altered atmospheric conditions

• 1 Altered atmospheric composition, associated with climate change, can modify herbivore population dynamics through CO₂ and/or O₃‐mediated changes in plant quality.
• 2 Although pea aphid Acyrthosiphon pisum genotypes exhibit intraspecific variation in population growth in response to atmospheric composition, the proximate mechanisms underlying this variation are largely unknown.
• 3 By rearing single (green, pink) and mixed (green + pink) pea aphid genotypes on red clover Trifolium pratense at the Aspen Free Air CO₂ and O₃ Enrichment (Aspen FACE) site, we assessed whether: (i) elevated CO₂ and/or O₃ concentrations alter aphid growth and development and (ii) individual aphid growth rates predict aphid population densities.
• 4 We showed that growth and development of individual green and pink aphids were not influenced by CO₂ and/or O₃ concentrations when reared as individual or mixed genotypes. Individual growth rates, however, did not predict population densities.
• 5 Reared as a single genotype, green pea aphid populations decreased in response to elevated CO₂ concentrations, but not in response to elevated CO₂ + O₃ concentrations. Pink pea aphid populations reared as a single genotype were unaffected by augmented CO₂ or O₃. Populations of mixed genotypes, however, were reduced under elevated CO₂ concentrations, irrespective of O₃ concentrations.
• 6 Herbivore population sizes may not readily be predicted from growth rates of individual organisms under atmospheric conditions associated with global climate change.

     

New genetic polymorphisms within ovine β- and αS2-caseins

Casein genes in ruminants are organized in a cluster including α_S1-casein (CSN1S1), β-casein (CSN2), α_S2-casein (CSN1S2), and κ-casein (CSN3). Considering the results obtained in cattle and goat species concerning the influence of genetic polymorphisms on milk composition, quality, and technological properties, research on the polymorphisms of ewe's milk has known a new impulse in the last decade. A total of 54 samples belonging to the Massese dairy breed, to the double pourpose (milk and meat) Garfagnina population and to the Pomarancina and Zerasca meat populations, reared in the Centre of Italy, were analysed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). New PCR-SSCP patterns were found in both CSN2 and CSN1S2 genes. Sequencing of the samples carrying the new patterns revealed 2 new variants at CSN2 gene. Frequencies of the 2 variants in the samples analysed were 0.18 and 0.02. The less common variant is characterized by a silent mutation in the triplet coding for Gln₁₉₂, whereas in the more frequent one a C to A transversion is responsible for the aminoacid exchange Leu₁₉₆ → Ile₁₉₆. At the CSN1S2 gene only a new variant was found with a frequency of 0.02. The variant is characterized by two linked mutations: a C to G transversion, responsible for the aminoacid change Asn₂₀₀ → Lys₂₀₀ already described at the protein level, and a T to A transversion at the 14th nucleotide of the 16th intron. The ovine caseins deserve a bigger attention that has to be directed to a complete characterization of the described variants and to the understanding of their functional meaning.     

Density-dependent changes in sex ratio in Colias lesbia (Lepidoptera: Pieridae)

Abstract.

• 1 The changes in sex ratio of a population of Colias lesbia were studied for four consecutive years.
• 2 A constant sex ratio was found in the samples taken in the 34 days following the last harvest of the alfalfa.
• 3 For the samples taken 35 or more days after the harvest the sex ratio decreases as the total number of adults caught increases.
• 4 The indirect evidence collected suggests that differences in emigration tendencies between sexes play a major role in determining the sex ratio in this species.

     

Demography of three populations of American mink Mustela vison in Europe

• 1 Demographic data on an invasive species of management concern, the American mink, are presented. Data were obtained on three feral mink populations in Europe distinguished by differences in the time elapsed since population establishment.
• 2 Demographic data are presented in the form of life tables, age–sex distributions and sex ratios. Mink lived a maximum of 6 years, and mortality of 1‐year‐olds and adults differed substantially between populations.
• 3 The data support the hypothesis that mink populations subject to culling have a higher proportion of young (less than 1 year old) to adults compared with non‐culled populations.

     

Female-biased sex ratio in a wild bruchid seed-predator, Kytorhinus sharpianus. I. Larval competition and other factors

Abstract.

• 1 A wild bruchid seed-predator, Kytorhinus sharpianus, has a complex life cycle consisting of bi- and trivoltinism on a wild leguminous plant, Sophola flavescens. Observations of adults showed significant female-biased sex ratios (from 1:2 to 1:6) for nine generations over 4 years.
• 2 To investigate the potential effects of larval competition on the sex ratio, we altered the number of hatched eggs per seed and counted emergent males and females under laboratory conditions. Although only one adult could emerge per seed, the ratio of the females that emerged increased with the number of hatched eggs per seed. However, the sex ratio was not significantly different from 1:1 in the case of one hatched egg per seed.
• 3 We dissected seeds bearing two hatched eggs at regular intervals, and classified the surviving and the dead larvae according to their developmental stage. Over time, one larva within each seed always survived, while the other larva died from the second to fourth instar before the seed resource became exhausted.
• 4 In order to study the effects of the difference in the stages of two larvae in a seed on the emergence sex ratio, we manipulated intervals between the first and second ovipositions in the laboratory. As the difference in developmental stages of the two larvae increased, the closer to 1:1 the emergence sex ratio became.
• 5 Field observations, however, showed that about 60% of infested seeds were bored by only one K.sharpianus larva. This suggests that female dominance in larval competition within a seed may be relatively unimportant in causing the female-biased sex ratio in the field.

     

The relation between body size and resistance to desiccation in two species of Zaprionus (Drosophilidae)

Abstract.

• 1 Resistance to desiccation and body size were studied in the drosophilid flies Zaprionus vittiger and Z.tuberculatus.
• 2 Populations in a hot dry low altitude area were compared with those in a nearby cooler wetter high altitude area in the north-eastern Transvaal of South Africa, using laboratory strains established from these populations.
• 3 No between-area differences were found for either body size or resistance to desiccation considered separately.
• 4 However, in Z.tuberculatus, regression analyses using strain mean values showed a strong positive correlation between the two characters amongst strains derived from low altitude populations but not amongst strains derived from high altitude populations.
• 5 It is concluded that differences of genetic organization have evolved between low and high altitude populations of Z.tuberculutus.
• 6 From differences between species and sexes it is concluded that both body size and some unknown factor related to sex may influence resistance of desiccation.

     

Modelling the Evolutionary Dynamics of Viruses within Their Hosts: A Case Study Using High-Throughput Sequencing

Uncovering how natural selection and genetic drift shape the evolutionary dynamics of virus populations within their hosts can pave the way to a better understanding of virus emergence. Mathematical models already play a leading role in these studies and are intended to predict future emergences. Here, using high-throughput sequencing, we analyzed the within-host population dynamics of four Potato virus Y (PVY) variants differing at most by two substitutions involved in pathogenicity properties. Model selection procedures were used to compare experimental results to six hypotheses regarding competitiveness and intensity of genetic drift experienced by viruses during host plant colonization. Results indicated that the frequencies of variants were well described using Lotka-Volterra models where the competition coefficients β_ij exerted by variant j on variant i are equal to their fitness ratio, r_j/r_i. Statistical inference allowed the estimation of the effect of each mutation on fitness, revealing slight (s = −0.45%) and high (s = −13.2%) fitness costs and a negative epistasis between them. Results also indicated that only 1 to 4 infectious units initiated the population of one apical leaf. The between-host variances of the variant frequencies were described using Dirichlet-multinomial distributions whose scale parameters, closely related to the fixation index F _ST, were shown to vary with time. The genetic differentiation of virus populations among plants increased from 0 to 10 days post-inoculation and then decreased until 35 days. Overall, this study showed that mathematical models can accurately describe both selection and genetic drift processes shaping the evolutionary dynamics of viruses within their hosts.     

Ecological genetics of Italian peach‐potato aphid (Myzus persicae) populations in relation to geography,dispersal and insecticide resistance as studied using microsatellite and resistance markers

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Variation in the life cycle of monogonont rotifers: Commitment to sex and emergence from diapause

1. A review of research on life-cycle events in field and laboratory populations of monogonont rotifers shows that there is great variation at multiple levels: (1) degree of sexual dimorphism; (2) occurrence and timing of sex; (3) propensity for sex during sexual periods; (4) factors controlling initiation of sex; and (5) timing and extent of emergence from diapause. There is no regular pattern where: (1) fertilised resting eggs hatch to start the growing season; (2) populations develop via female parthenogenesis during favourable conditions; and then (3) bisexual reproduction with resting-egg production occurs during later, unfavourable conditions.
2. Sexual reproduction in natural populations can occur throughout much of the growing season, be restricted to some period(s) during the growing season, or be completely absent. During sexual reproduction in both natural and laboratory populations, only some fraction of females produces males or resting eggs. This bet-hedging strategy can prevent a population crash and permits future population growth via female parthenogenesis. Selection against sexual reproduction, and rapid loss of sex, can occur.
3. Laboratory experiments with pond-dwelling species have identified specific environmental factors that induce sex in different species: (1) increasing population density; (2) dietary tocopherol (vitamin E) and (3) long photoperiods. These factors generally are associated with favourable conditions for population growth and production of energy-rich resting eggs: (1) large population size; (2) high probability of contacts between males and fertilisable females; and (3) nutritious diets. Endogenous factors can inhibit responses to these environmental inducers, and thus favour female parthenogenesis.
4. The timing of resting-egg hatching depends on: (1) occurrence of specific environmental conditions; (2) the minimum duration of obligate diapause; and (3) the genotype and physiology of females producing resting eggs. Hatching may occur shortly after oviposition, after a long diapause before or at the start of a new growing season, or throughout the growing season. Hatching can be massive and contribute substantially to population growth and genetic diversity.
5. Areas for future research include: (1) determining the timing and extent of sex and resting-egg hatching in more natural populations, especially those that are marine, benthic, sessile, and interstitial; and (2) identifying environmental and physiological factors controlling these events.

     

Diversity,origins and virulence of <Emphasis Type="Italic">Avipoxviruses</Emphasis> in Hawaiian Forest Birds

We cultured avian pox (Avipoxvirus spp.) from lesions collected on Hawai‘i, Maui, Moloka‘i, and ‘Oahu in the Hawaiian Islands from 15 native or non-native birds representing three avian orders. Phylogenetic analysis of a 538 bp fragment of the gene encoding the virus 4b core polypeptide revealed two distinct variant clusters, with sequences from chickens (fowlpox) forming a third distinct basal cluster. Pox isolates from one of these two clusters appear closely related to canarypox and other passerine pox viruses, while the second appears more specific to Hawai‘i. There was no evidence that birds were infected simultaneously with multiple pox virus variants based on evaluation of multiples clones from four individuals. No obvious temporal or geographic associations were observed and strict host specificity was not apparent among the 4b-defined field isolates. We amplified a 116 bp 4b core protein gene fragment from an ‘Elepaio (Chasiempis sandwichensis) collected in 1900 on Hawai‘i Island that clustered closely with the second of the two variants, suggesting that this variant has been in Hawai‘i for at least 100 years. The high variation detected between the three 4b clusters provides evidence for multiple, likely independent introductions, and does not support the hypothesis of infection of native species through introduction of infected fowl. Preliminary experimental infections in native Hawai‘i ‘Amakihi (Hemignathus virens) suggest that the 4b-defined variants may be biologically distinct, with one variant appearing more virulent. These pox viruses may interact with avian malaria (Plasmodium relictum), another introduced pathogen in Hawaiian forest bird populations, through modulation of host immune responses.