The evolution of costly mate choice against segregation distorters

The evolution of female preference for male genetic quality remains a controversial topic in sexual selection research. One well‐known problem, known as the lek paradox, lies in understanding how variation in genetic quality is maintained in spite of natural selection and sexual selection against low‐quality alleles. Here, we theoretically investigate a scenario where females pay a direct fitness cost to avoid males carrying an autosomal segregation distorter. We show that preference evolution is greatly facilitated under such circumstances. Because the distorter is transmitted in a non‐Mendelian fashion, it can be maintained in the population despite directional sexual selection. The preference helps females avoid fitness costs associated with the distorter. Interestingly, we find that preference evolution is limited if the choice allele induces a very strong preference or if distortion is very strong. Moreover, the preference can only persist in the presence of a signal that reliably indicates a male's distorter genotype. Hence, even in a system where the lek paradox does not play a major role, costly preferences can only spread under specific circumstances. We discuss the importance of distorter systems for the evolution of costly female choice and potential implications for the use of artificial distorters in pest control.     

Sperm competition suppresses gene drive among experimentally evolving populations of house mice

Drive genes are genetic elements that manipulate the 50% ratio of Mendelian inheritance in their own favour, allowing them to rapidly propagate through populations. The action of drive genes is often hidden, making detection and identification inherently difficult. Yet drive genes can have profound evolutionary consequences for the populations that harbour them: most known drivers are detrimental to organismal gamete development, reproduction and survival. In this study, we identified the presence of a well‐known drive gene called t haplotype post hoc in eight replicate selection lines of house mice that had been evolving under enforced monandry or polyandry for 20 generations. Previous work on these selection lines reported an increase in sperm competitive ability in males evolving under polyandry. Here, we show that this evolutionary response can be partly attributed to gene drive. We demonstrate that drive‐carrying males are substantially compromised in their sperm competitive ability. As a consequence, we found that t frequencies declined significantly in the polyandrous lines while remaining at stable, high levels in the monandrous lines. For the first time in a vertebrate, we thus provide direct experimental evidence that the mating system of a species can have important repercussions on the spread of drive genes over evolutionary relevant timescales. Moreover, our work highlights how the covert action of drive genes can have major, potentially unintended impact on our study systems.     

A Phylogeny-aware GWAS Framework to Correct for Heritable Pathogen Effects on Infectious Disease Traits

Infectious diseases are particularly challenging for genome-wide association studies (GWAS) because genetic effects from two organisms (pathogen and host) can influence a trait. Traditional GWAS assume individual samples are independent observations. However, pathogen effects on a trait can be heritable from donor to recipient in transmission chains. Thus, residuals in GWAS association tests for host genetic effects may not be independent due to shared pathogen ancestry. We propose a new method to estimate and remove heritable pathogen effects on a trait based on the pathogen phylogeny prior to host GWAS, thus restoring independence of samples. In simulations, we show this additional step can increase GWAS power to detect truly associated host variants when pathogen effects are highly heritable, with strong phylogenetic correlations. We applied our framework to data from two different host–pathogen systems, HIV in humans and X. arboricola in A. thaliana. In both systems, the heritability and thus phylogenetic correlations turn out to be low enough such that qualitative results of GWAS do not change when accounting for the pathogen shared ancestry through a correction step. This means that previous GWAS results applied to these two systems should not be biased due to shared pathogen ancestry. In summary, our framework provides additional information on the evolutionary dynamics of traits in pathogen populations and may improve GWAS if pathogen effects are highly phylogenetically correlated amongst individuals in a cohort.     

Antibodies against beta-amyloid slow cognitive decline in Alzheimer's disease

To test whether antibodies against beta-amyloid are effective in slowing progression of Alzheimer's disease, we assessed cognitive functions in 30 patients who received a prime and a booster immunization of aggregated Abeta(42) over a 1 year period in a placebo-controlled, randomized trial. Twenty patients generated antibodies against beta-amyloid, as determined by tissue amyloid plaque immunoreactivity assay. Patients who generated such antibodies showed significantly slower rates of decline of cognitive functions and activities of daily living, as indicated by the Mini Mental State Examination, the Disability Assessment for Dementia, and the Visual Paired Associates Test of delayed recall from the Wechsler Memory Scale, as compared to patients without such antibodies. These beneficial clinical effects were also present in two of three patients who had experienced transient episodes of immunization-related aseptic meningoencephalitis. Our results establish that antibodies against beta-amyloid plaques can slow cognitive decline in patients with Alzheimer's disease.     

Disentangling Human Tolerance and Resistance Against HIV

In ecology, “disease tolerance” is defined as an evolutionary strategy of hosts against pathogens, characterized by reduced or absent pathogenesis despite high pathogen load. To our knowledge, tolerance has to date not been quantified and disentangled from host resistance to disease in any clinically relevant human infection. Using data from the Swiss HIV Cohort Study, we investigated if there is variation in tolerance to HIV in humans and if this variation is associated with polymorphisms in the human genome. In particular, we tested for associations between tolerance and alleles of the Human Leukocyte Antigen (HLA) genes, the CC chemokine receptor 5 (CCR5), the age at which individuals were infected, and their sex. We found that HLA-B alleles associated with better HIV control do not confer tolerance. The slower disease progression associated with these alleles can be fully attributed to the extent of viral load reduction in carriers. However, we observed that tolerance significantly varies across HLA-B genotypes with a relative standard deviation of 34%. Furthermore, we found that HLA-B homozygotes are less tolerant than heterozygotes. Lastly, tolerance was observed to decrease with age, resulting in a 1.7-fold difference in disease progression between 20 and 60-y-old individuals with the same viral load. Thus, disease tolerance is a feature of infection with HIV, and the identification of the mechanisms involved may pave the way to a better understanding of pathogenesis.     

Spatial modelling of ecological indicator values improves predictions of plant distributions in complex landscapes

Ecologically meaningful predictors are often neglected in plant distribution studies, resulting in incomplete niche quantification and low predictive power of species distribution models (SDMs). Because environmental data are rare and expensive to collect, and because their relationship with local climatic and topographic conditions are complex, mapping them over large geographic extents and at high spatial resolution remains a major challenge. Here, we propose to derive environmental data layers by mapping ecological indicator values in space. We combined ~6 million plant occurrences with expert-based plant ecological indicator values (EIVs) of 3600 species in Switzerland. EIVs representing local soil properties (pH, moisture, moisture variability, aeration, humus and nutrients) and climatic conditions (continentality, light) were modelled at 93 m spatial resolution with the Random Forest algorithm and 16 predictors representing meso-climate, land use, topography and geology. Models were evaluated and predictions of EIVs were compared with soil inventory data. We mapped each EIV separately and evaluated EIV importance in explaining the distribution of 500 plant species using SDMs with a set of 30 environmental predictors. Finally, we tested how they improve an ensemble of SDMs compared to a standard set of predictors for ca 60 plant species. All EIV models showed excellent performance (|r| > 0.9) and predictions were correlated reasonably (|r| > 0.4) to soil properties measured in the field. Resulting EIV maps were among the most important predictors in SDMs. Also, in ensemble SDMs overall predictive performance increased, mainly through improved model specificity reducing species range overestimation. Combining large citizen science databases to expert-based EIVs is a powerful and cost–effective approach for generalizing local edaphic and climatic conditions over large areas. Producing ecologically meaningful predictors is a first step for generating better predictions of species distribution which is of main importance for decision makers in conservation and environmental management projects.     

Polyandry and the decrease of a selfish genetic element in a wild house mouse population

Despite deleterious effects on individuals, the t haplotype is a selfish genetic element present in many house mouse populations. By distorting the transmission ratio, +/t males transmit the t haplotype to up to 90% of their offspring. However, t/t individuals perish in utero. Theoretical models based on these properties predict a much higher t frequency than observed, leading to the t paradox. Here, we use empirical field data and theoretical approaches to investigate whether polyandry is a female counterstrategy against the negative fitness consequences of such distorters. We found a significant decrease of the t frequency over a period of 5.5 years that cannot be explained by the effect of transmission ratio distortion and recessive lethals, despite significantly higher life expectancy of +/t females compared to +/+ females. We quantified life-history data and homozygous and heterozygous fitness effects. Population subdivision and inbreeding were excluded as evolutionary forces influencing the t system. The possible influence of polyandry on the t system was then investigated by applying a stochastic model to this situation. Simulations show that polyandry can explain the observed t dynamics, making it a biologically plausible explanation for low t frequencies in natural populations in general.     

Early antiretroviral therapy during primary HIV-1 infection results in a transient reduction of the viral setpoint upon treatment interruption

Background

Long-term benefits of combination antiretroviral therapy (cART) initiation during primary HIV-1 infection are debated.

Methods

The evolution of plasma HIV-RNA (432 measurements) and cell-associated HIV-DNA (325 measurements) after cessation of cART (median exposure 18 months) was described for 33 participants from the Zurich Primary HIV Infection Study using linear regression and compared with 545 measurements from 79 untreated controls with clinically diagnosed primary HIV infection, respectively a known date for seroconversion.

Results

On average, early treated individuals were followed for 37 months (median) after cART cessation; controls had 34 months of pre-cART follow-up. HIV-RNA levels one year after cART interruption were −0.8 log₁₀ copies/mL [95% confidence interval −1.2;−0.4] lower in early treated patients compared with controls, but this difference was no longer statistically significant by year three of follow-up (−0.3 [−0.9; 0.3]). Mean HIV-DNA levels rebounded from 2 log₁₀ copies [1.8; 2.3] on cART to a stable plateau of 2.7 log₁₀ copies [2.5; 3.0] attained 1 year after therapy stop, which was not significantly different from cross-sectional measurements of 9 untreated members of the control group (2.8 log₁₀ copies [2.5; 3.1]).

Conclusions

The rebound dynamics of viral markers after therapy cessation suggest that early cART may indeed limit reservoir size of latently infected cells, but that much of the initial benefits are only transient. Owing to the non-randomized study design the observed treatment effects must be interpreted with caution.     

Dynamics of a human‐modified tropical peat swamp forest revealed by repeat lidar surveys

Tropical peat swamp forests (PSFs) are globally important carbon stores under threat. In Southeast Asia, 35% of peatlands had been drained and converted to plantations by 2010, and much of the remaining forest had been logged, contributing significantly to global carbon emissions. Yet, tropical forests have the capacity to regain biomass quickly and forests on drained peatlands may grow faster in response to soil aeration, so the net effect of humans on forest biomass remains poorly understood. In this study, two lidar surveys (made in 2011 and 2014) are compared to map forest biomass dynamics across 96 km² of PSF in Kalimantan, Indonesia. The peatland is now legally protected for conservation, but large expanses were logged under concessions until 1998 and illegal logging continues in accessible portions. It was hypothesized that historically logged areas would be recovering biomass while recently logged areas would be losing biomass. We found that historically logged forests were recovering biomass near old canals and railways used by the concessions. Lidar detected substantial illegal logging activity—579 km of logging canals were located beneath the canopy. Some patches close to these canals have been logged in the 2011–2104 period (i.e. substantial biomass loss) but, on aggregate, these illegally logged regions were also recovering. Unexpectedly, rapid growth was also observed in intact forest that had not been logged and was over a kilometre from the nearest known canal, perhaps in response to greater aeration of surface peat. Comparing these results with flux measurements taken at other nearby sites, we find that carbon sequestration in above‐ground biomass may have offset roughly half the carbon efflux from peat oxidation. This study demonstrates the power of repeat lidar survey to map fine‐scale forest dynamics in remote areas, revealing previously unrecognized impacts of anthropogenic global change.