Evidence for Variation in the Effective Population Size of Animal Mitochondrial DNA

Background

It has recently been shown that levels of diversity in mitochondrial DNA are remarkably constant across animals of diverse census population sizes and ecologies, which has led to the suggestion that the effective population of mitochondrial DNA may be relatively constant.

Results

Here we present several lines of evidence that suggest, to the contrary, that the effective population size of mtDNA does vary, and that the variation can be substantial. First, we show that levels of mitochondrial and nuclear diversity are correlated within all groups of animals we surveyed. Second, we show that the effectiveness of selection on non-synonymous mutations, as measured by the ratio of the numbers of non-synonymous and synonymous polymorphisms, is negatively correlated to levels of mitochondrial diversity. Finally, we estimate the effective population size of mitochondrial DNA in selected mammalian groups and show that it varies by at least an order of magnitude.

Conclusions

We conclude that there is variation in the effective population size of mitochondria. Furthermore we suggest that the relative constancy of DNA diversity may be due to a negative correlation between the effective population size and the mutation rate per generation.     

Selection dramatically reduces effective population size in HIV-1 infection

Background  

In HIV-1 evolution, a 100–100,000 fold discrepancy between census size and effective population size (N _e ) has been noted. Although it is well known that selection can reduce N _e , high in vivo mutation and recombination rates complicate attempts to quantify the effects of selection on HIV-1 effective size.     

Methods to estimate effective population size using pedigree data: Examples in dog,sheep, cattle and horse

Background

Effective population sizes of 140 populations (including 60 dog breeds, 40 sheep breeds, 20 cattle breeds and 20 horse breeds) were computed using pedigree information and six different computation methods. Simple demographical information (number of breeding males and females), variance of progeny size, or evolution of identity by descent probabilities based on coancestry or inbreeding were used as well as identity by descent rate between two successive generations or individual identity by descent rate.

Results

Depending on breed and method, effective population sizes ranged from 15 to 133 056, computation method and interaction between computation method and species showing a significant effect on effective population size (P < 0.0001). On average, methods based on number of breeding males and females and variance of progeny size produced larger values (4425 and 356, respectively), than those based on identity by descent probabilities (average values between 93 and 203). Since breeding practices and genetic substructure within dog breeds increased inbreeding, methods taking into account the evolution of inbreeding produced lower effective population sizes than those taking into account evolution of coancestry. The correlation level between the simplest method (number of breeding males and females, requiring no genealogical information) and the most sophisticated one ranged from 0.44 to 0.60 according to species.

Conclusions

When choosing a method to compute effective population size, particular attention should be paid to the species and the specific genetic structure of the population studied.     

Demographic costs of inbreeding revealed by sex-specific genetic rescue effects

Background  

Inbreeding can slow population growth and elevate extinction risk. A small number of unrelated immigrants to an inbred population can substantially reduce inbreeding and improve fitness, but little attention has been paid to the sex-specific effects of immigrants on such "genetic rescue". We conducted two subsequent experiments to investigate demographic consequences of inbreeding and genetic rescue in guppies.     

Estimating the Sizes of Populations at High Risk for HIV: A Comparison Study

Objectives

Behavioral interventions are effective strategies for HIV/AIDS prevention and control. However, implementation of such strategies relies heavily on the accurate estimation of the high-risk population size. The multiplier method and generalized network scale-up method were recommended to estimate the population size of those at high risk for HIV by UNAIDS/WHO in 2003 and 2010, respectively. This study aims to assess and compare the two methods for estimating the size of populations at high risk for HIV, and to provide practical guidelines and suggestions for implementing the two methods.

Methods

Studies of the multiplier method used to estimate the population prevalence of men who have sex with men in China published between July 1, 2003 and July 1, 2013 were reviewed. The generalized network scale-up method was applied to estimate the population prevalence of men who have sex with men in the urban district of Taiyuan, China.

Results

The median of studies using the multiplier method to estimate the population prevalence of men who have sex with men in China was 4–8 times lower than the national level estimate. Meanwhile, the estimate of the generalized network scale-up method fell within the range of national level estimate.

Conclusions

When high-quality existing data are not readily available, the multiplier method frequently yields underestimated results. We thus suggest that the generalized network scale-up method is preferred when sampling frames for the general population and accurate demographic information are available.     

A Large Plasmodium vivax Reservoir and Little Population Structure in the South Pacific

Introduction

The importance of Plasmodium vivax in malaria elimination is increasingly being recognized, yet little is known about its population size and population genetic structure in the South Pacific, an area that is the focus of intensified malaria control.

Methods

We have genotyped 13 microsatellite markers in 295 P. vivax isolates from four geographically distinct sites in Papua New Guinea (PNG) and one site from Solomon Islands, representing different transmission intensities.

Results

Diversity was very high with expected heterozygosity values ranging from 0.62 to 0.98 for the different markers. Effective population size was high (12′872 to 19′533 per site). In PNG population structuring was limited with moderate levels of genetic differentiation. F _ST values (adjusted for high diversity of markers) were 0.14–0.15. Slightly higher levels were observed between PNG populations and Solomon Islands (F _ST = 0.16).

Conclusions

Low levels of population structure despite geographical barriers to transmission are in sharp contrast to results from regions of low P. vivax endemicity. Prior to intensification of malaria control programs in the study area, parasite diversity and effective population size remained high.     

Why Publishing Everything Is More Effective than Selective Publishing of Statistically Significant Results

Background

De Winter and Happee [1] examined whether science based on selective publishing of significant results may be effective in accurate estimation of population effects, and whether this is even more effective than a science in which all results are published (i.e., a science without publication bias). Based on their simulation study they concluded that “selective publishing yields a more accurate meta-analytic estimation of the true effect than publishing everything, (and that) publishing nonreplicable results while placing null results in the file drawer can be beneficial for the scientific collective” (p.4).

Methods and Findings

Using their scenario with a small to medium population effect size, we show that publishing everything is more effective for the scientific collective than selective publishing of significant results. Additionally, we examined a scenario with a null effect, which provides a more dramatic illustration of the superiority of publishing everything over selective publishing.

Conclusion

Publishing everything is more effective than only reporting significant outcomes.     

Size control in growing yeast and mammalian cells

Background  

In a recent publication it was claimed that cultured mammalian cells, in contrast to yeasts, maintain a constant size distribution in the population without a size checkpoint. This inference may be challengeable.     

Application of Network Scale Up Method in the Estimation of Population Size for Men Who Have Sex with Men in Shanghai,China

Background

Men who have sex with men (MSM) are at high risk of HIV infection. For developing proper interventions, it is important to know the size of MSM population. However, size estimation of MSM populations is still a significant public health challenge due to high cost, hard to reach and stigma associated with the population.

Objectives

We aimed to estimate the social network size (c value) in general population and the size of MSM population in Shanghai, China by using the net work scale-up method.

Methods

A multistage random sampling was used to recruit participants aged from 18 to 60 years who had lived in Shanghai for at least 6 months. The “known population method” with adjustment of backward estimation and regression model was applied to estimate the c value. And the MSM population size was further estimated using an adjusted c value taking into account for the transmission effect through social respect level towards MSM.

Results

A total of 4017 participants were contacted for an interview, and 3907 participants met the inclusion criterion. The social network size (c value) of participants was 236 after adjustment. The estimated size of MSM was 36354 (95% CI: 28489–44219) for the male Shanghaies aged 18 to 60 years, and the proportion of MSM among the total male population aged 18 to 60 years in Shanghai was 0.28%.

Conclusions

We employed the network scale-up method and used a wide range of data sources to estimate the size of MSM population in Shanghai, which is useful for HIV prevention and intervention among the target population.     

Inference of demographic history from genealogical trees using reversible jump Markov chain Monte Carlo

Background  

Coalescent theory is a general framework to model genetic variation in a population. Specifically, it allows inference about population parameters from sampled DNA sequences. However, most currently employed variants of coalescent theory only consider very simple demographic scenarios of population size changes, such as exponential growth.     

Population size estimation of men who have sex with men through the network scale-up method in Japan

Background

Men who have sex with men (MSM) are one of the groups most at risk for HIV infection in Japan. However, size estimates of MSM populations have not been conducted with sufficient frequency and rigor because of the difficulty, high cost and stigma associated with reaching such populations. This study examined an innovative and simple method for estimating the size of the MSM population in Japan. We combined an internet survey with the network scale-up method, a social network method for estimating the size of hard-to-reach populations, for the first time in Japan.

Methods and Findings

An internet survey was conducted among 1,500 internet users who registered with a nationwide internet-research agency. The survey participants were asked how many members of particular groups with known population sizes (firepersons, police officers, and military personnel) they knew as acquaintances. The participants were also asked to identify the number of their acquaintances whom they understood to be MSM. Using these survey results with the network scale-up method, the personal network size and MSM population size were estimated. The personal network size was estimated to be 363.5 regardless of the sex of the acquaintances and 174.0 for only male acquaintances. The estimated MSM prevalence among the total male population in Japan was 0.0402% without adjustment, and 2.87% after adjusting for the transmission error of MSM.

Conclusions

The estimated personal network size and MSM prevalence seen in this study were comparable to those from previous survey results based on the direct-estimation method. Estimating population sizes through combining an internet survey with the network scale-up method appeared to be an effective method from the perspectives of rapidity, simplicity, and low cost as compared with more-conventional methods.     

Fecundity and longevity of roaming dogs in Jaipur,India

Background

Estimates of demographic parameters, such as age-specific survival and fecundity, age at first pregnancy and litter size, are required for roaming dogs (i.e. dogs that are neither confined nor restricted) to assess the likely effect of proposed methods of population control. Data resulting from individual identification of dogs spayed as part of an Animal Birth Control (ABC) programme in Jaipur, India, are used to derive such parameters for the roaming dog population of that city.

Results

The percentage of females becoming pregnant in any given year was estimated by inspection of over 25,000 females caught for spaying from 1995 to 2006. The point estimate is 47.5% with a 95% confidence interval from 44% to 51%. Adult annual survival of spayed females was estimated by recapture of 62 spayed females from 2002 to 2006. The point estimate is 0.70 (95% confidence interval from 0.62 to 0.78), corresponding to an expected total lifespan of 3.8 years for a spayed female at one year old.

Conclusion

Recording the pregnancy status of dogs collected for spaying and individual marking of dogs released following spaying can provide estimates of some of the demographic parameters essential for predicting the future effectiveness of an ABC programme. Further, we suggest that recording the number and location of spayed and unspayed dogs encountered by the catching teams could be the most effective way to monitor the size and composition of the roaming dog population.

     

Population Size Estimation of Men Who Have Sex with Men in Tbilisi,Georgia; Multiple Methods and Triangulation of Findings

Introduction

An accurate estimation of the population size of men who have sex with men (MSM) is critical to the success of HIV program planning and to monitoring of the response to epidemic as a whole, but is quite often missing. In this study, our aim was to estimate the population size of MSM in Tbilisi, Georgia and compare it with other estimates in the region.

Methods

In the absence of a gold standard for estimating the population size of MSM, this study reports a range of methods, including network scale-up, mobile/web apps multiplier, service and unique object multiplier, network-based capture-recapture, Handcock RDS-based and Wisdom of Crowds methods. To apply all these methods, two surveys were conducted: first, a household survey among 1,015 adults from the general population, and second, a respondent driven sample of 210 MSM. We also conducted a literature review of MSM size estimation in Eastern European and Central Asian countries.

Results

The median population size of MSM generated from all previously mentioned methods was estimated to be 5,100 (95% Confidence Interval (CI): 3,243 ~ 9,088). This corresponds to 1.42% (95%CI: 0.9% ~ 2.53%) of the adult male population in Tbilisi.

Conclusion

Our size estimates of the MSM population (1.42% (95%CI: 0.9% ~ 2.53%) of the adult male population in Tbilisi) fall within ranges reported in other Eastern European and Central Asian countries. These estimates can provide valuable information for country level HIV prevention program planning and evaluation. Furthermore, we believe, that our results will narrow the gap in data availability on the estimates of the population size of MSM in the region.     

Population structure of the malaria vector Anopheles sinensis (Diptera: Culicidae) in China: two gene pools inferred by microsatellites

Background

Anopheles sinensis is a competent malaria vector in China. An understanding of vector population structure is important to the vector-based malaria control programs. However, there is no adequate data of A. sinensis population genetics available yet.

Methodology/Principal Findings

This study used 5 microsatellite loci to estimate population genetic diversity, genetic differentiation and demographic history of A. sinensis from 14 representative localities in China. All 5 microsatellite loci were highly polymorphic across populations, with high allelic richness and heterozygosity. Hardy–Weinberg disequilibrium was found in 12 populations associated with heterozygote deficits, which was likely caused by the presence of null allele and the Wahlund effect. Bayesian clustering analysis revealed two gene pools, grouping samples into two population clusters; one includes six and the other includes eight populations. Out of 14 samples, six samples were mixed with individuals from both gene pools, indicating the coexistence of two genetic units in the areas sampled. The overall differentiation between two genetic pools was moderate (F _ST = 0.156). Pairwise differentiation between populations were lower within clusters (F _ST = 0.008–0.028 in cluster I and F _ST = 0.004–0.048 in cluster II) than between clusters (F _ST = 0.120–0.201). A reduced gene flow (Nm = 1–1.7) was detected between clusters. No evidence of isolation by distance was detected among populations neither within nor between the two clusters. There are differences in effective population size (Ne = 14.3-infinite) across sampled populations.

Conclusions/Significance

Two genetic pools with moderate genetic differentiation were identified in the A. sinensis populations in China. The population divergence was not correlated with geographic distance or barrier in the range. Variable effective population size and other demographic effects of historical population perturbations could be the factors affecting the population differentiation. The structured populations may limit the migration of genes under pressures/selections, such as insecticides and immune genes against malaria.     

An Analysis of Diet Quality,How It Controls Fatty Acid Profiles,Isotope Signatures and Stoichiometry in the Malaria Mosquito Anopheles arabiensis

Background

Knowing the underlying mechanisms of mosquito ecology will ensure effective vector management and contribute to the overall goal of malaria control. Mosquito populations show a high degree of population plasticity in response to environmental variability. However, the principle factors controlling population size and fecundity are for the most part unknown. Larval habitat and diet play a crucial role in subsequent mosquito fitness. Developing the most competitive insects for sterile insect technique programmes requires a “production” orientated perspective, to deduce the most effective larval diet formulation; the information gained from this process offers us some insight into the mechanisms and processes taking place in natural native mosquito habitats.

Methodology/Principal Findings

Fatty acid profiles and de-novo or direct assimilation pathways, of whole-individual mosquitoes reared on a range of larval diets were determined using pyrolysis gas chromatograph/mass spectrometry. We used elemental analysis and isotope ratio mass spectrometry to measure individual-whole-body carbon, nitrogen and phosphorous values and to assess the impact of dietary quality on subsequent population stoichiometry, size, quality and isotopic signature. Diet had the greatest impact on fatty acid (FA) profiles of the mosquitoes, which exhibited a high degree of dietary routing, characteristic of generalist feeders. De-novo synthesis of a number of important FAs was observed. Mosquito C:N stoichiometry was fixed in the teneral stage. Dietary N content had significant influence on mosquito size, and P was shown to be a flexible pool which limited overall population size.

Conclusions/Significance

Direct routing of FAs was evident but there was ubiquitous de-novo synthesis suggesting mosquito larvae are competent generalist feeders capable of survival on diet with varying characteristics. It was concluded that nitrogen availability in the larval diet controlled teneral mosquito size and that teneral CN ratio is a sex- and species-specific fixed parameter. This finding has significant implications for overall mosquito competitiveness and environmental management.     

When Stress Predicts a Shrinking Gene Pool,Trading Early Reproduction for Longevity Can Increase Fitness,Even with Lower Fecundity

Background

Stresses like dietary restriction or various toxins increase lifespan in taxa as diverse as yeast, Caenorhabditis elegans, Drosophila and rats, by triggering physiological responses that also tend to delay reproduction. Food odors can reverse the effects of dietary restriction, showing that key mechanisms respond to information, not just resources. Such environmental cues can predict population trends, not just individual prospects for survival and reproduction. When population size is increasing, each offspring produced earlier makes a larger proportional contribution to the gene pool, but the reverse is true when population size is declining.

Principal Findings

We show mathematically that natural selection can favor facultative delay in reproduction when environmental cues predict a decrease in total population size, even if lifetime fecundity decreases with delay. We also show that increased reproduction from waiting for better conditions does not increase fitness (proportional representation) when the whole population benefits similarly.

Conclusions

We conclude that the beneficial effects of stress on longevity (hormesis) in diverse taxa are a side-effect of delaying reproduction in response to environmental cues that population size is likely to decrease. The reversal by food odors of the effects of dietary restriction can be explained as a response to information that population size is less likely to decrease, reducing the chance that delaying reproduction will increase fitness.     

Inference on population history and model checking using DNA sequence and microsatellite data with the software DIYABC (v1.0)

Background  

Approximate Bayesian computation (ABC) is a recent flexible class of Monte-Carlo algorithms increasingly used to make model-based inference on complex evolutionary scenarios that have acted on natural populations. The software DIYABC offers a user-friendly interface allowing non-expert users to consider population histories involving any combination of population divergences, admixtures and population size changes. We here describe and illustrate new developments of this software that mainly include (i) inference from DNA sequence data in addition or separately to microsatellite data, (ii) the possibility to analyze five categories of loci considering balanced or non balanced sex ratios: autosomal diploid, autosomal haploid, X-linked, Y-linked and mitochondrial, and (iii) the possibility to perform model checking computation to assess the "goodness-of-fit" of a model, a feature of ABC analysis that has been so far neglected.     

SPEM dysfunction and general schizotypy as measured by the SSQ: a controlled study

Background

SPEM dysfunction is a well-known phenomenon in schizophrenia. The principal aim of the present study was to examine whether SPEM dysfunction is already observable in subjects scoring high on a specific measure of schizotypy (SSQ General Schizotypy) that was selected because of its intimate relationship with schizophrenic prodromal unfolding.

Methods

Applying ANOVAs, we determined the relationship of subjects' scores on SSQ General Schizotypy and eye movements elicited by targets of different speed. We also examined whether there exists an association between our schizotypy measure and pupil size.

Results

We found more SPEM dysfunction in subjects scoring high on SSQ General Schizotypy than in subjects scoring average on that factor, irrespective of the speed of the target. No relationship was found between baseline pupil size and General Schizotypy.

Conclusion

The present study provides additional evidence that SPEM dysfunction is associated with schizotypic features that precede the onset of schizophrenia and is already observable in general population subjects that show these features.     

Rapid loss of genetic variation in a founding population of Primula elatior (Primulaceae) after colonization

Background and Aims

Land-use changes and associated extinction/colonization dynamics can have a large impact on population genetic diversity of plant species. The aim of this study was to investigate genetic diversity in a founding population of the self-incompatible forest herb Primula elatior and to elucidate the processes that affect genetic diversity shortly after colonization.

Methods

AFLP markers were used to analyse genetic diversity across three age classes and spatial genetic structure within a founding population of P. elatior in a recently established stand in central Belgium. Parentage analyses were used to assess the amount of gene flow from outside the population and to investigate the contribution of mother plants to future generations.

Results

The genetic diversity of second and third generation plants was significantly reduced compared with that of first generation plants. Significant spatial genetic structure was observed. Parentage analyses showed that <20 % of the youngest individuals originated from parents outside the study population and that >50 % of first and second generation plants did not contribute to seedling recruitment.

Conclusions

These results suggest that a small effective population size and genetic drift can lead to rapid decline of genetic diversity of offspring in founding populations shortly after colonization. This multigenerational study also highlights that considerable amounts of gene flow seem to be required to counterbalance genetic drift and to sustain high levels of genetic diversity after colonization in recently established stands.Key words: AFLP, colonization, forest regeneration, genetic diversity, genetic drift, parentage analysis, spatial genetic structure     

Effects of pathogen dependency in a multi-pathogen infectious disease system including population level heterogeneity – a simulation study

Background

Increased computational resources have made individual based models popular for modelling epidemics. They have the advantage of incorporating heterogeneous features, including realistic population structures (like e.g. households). Existing stochastic simulation studies of epidemics, however, have been developed mainly for incorporating single pathogen scenarios although the effect of different pathogens might directly or indirectly (e.g. via contact reductions) effect the spread of each pathogen. The goal of this work was to simulate a stochastic agent based system incorporating the effect of multiple pathogens, accounting for the household based transmission process and the dependency among pathogens.

Methods

With the help of simulations from such a system, we observed the behaviour of the epidemics in different scenarios. The scenarios included different household size distributions, dependency versus independency of pathogens, and also the degree of dependency expressed through household isolation during symptomatic phase of individuals. Generalized additive models were used to model the association between the epidemiological parameters of interest on the variation in the parameter values from the simulation data. All the simulations and statistical analyses were performed using R 3.4.0.

Results

We demonstrated the importance of considering pathogen dependency using two pathogens, and showing the difference when considered independent versus dependent. Additionally for the general scenario with more pathogens, the assumption of dependency among pathogens and the household size distribution in the population cohort was found to be effective in containing the epidemic process. Additionally, populations with larger household sizes reached the epidemic peak faster than societies with smaller household sizes but dependencies among pathogens did not affect this outcome significantly. Larger households had more infections in all population cohort examples considered in our simulations. Increase in household isolation coefficient for pathogen dependency also could control the epidemic process.

Conclusion

Presence of multiple pathogens and their interaction can impact the behaviour of an epidemic across cohorts with different household size distributions. Future household cohort studies identifying multiple pathogens will provide useful data to verify the interaction processes in such an infectious disease system.