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opencc-zeroSep 2020View details →

Data associated with 'Metformin rescues Parkinson's disease phenotypes caused by hyperactive mitochondria'

Metabolic dysfunction occurs in many age-related neurodegenerative diseases, yet its role in disease etiology remains poorly understood. We recently discovered a potential causal link between the branched-chain amino acid transferase, BCAT-1, and the neurodegenerative movement disorder, Parkinson's disease (PD). RNAi-mediated knockdown of C. elegans bcat-1 recapitulates PD-like features, including progressive motor deficits and neurodegeneration with age, yet the underlying mechanisms have remained unknown. Using transcriptomic, metabolomic, and imaging approaches, we show here that bcat-1 knockdown increases mitochondrial respiration and induces oxidative damage in neurons through mTOR-independent mechanisms. Increased mitochondrial respiration, or 'mitochondrial hyperactivity,' is required for bcat-1(RNAi) neurotoxicity. Moreover, we show that post-disease onset administration of the type 2 diabetes medication, metformin, reduces mitochondrial respiration to control levels and significantly improves both motor function and neuronal viability. Together, our findings suggest that mitochondrial hyperactivity may be an early event in PD pathogenesis, and strategies aimed at reducing mitochondrial respiration may constitute a surprising new avenue for PD treatment.

opencc-zeroOct 2020View details →

The evolution of phenotypic novelty through the genetic assimilation of broken symmetry

Most animals are symmetrical; however, widespread and impressive cases occur where symmetry has been broken. Breaks in symmetry can occur as anti-symmetry, where 50% of the population have the left side enlarged and 50% the right, or through directional asymmetry where the entire population is biased either to the left or the right. Such broken symmetry represents a novel phenotype that is challenging to explain from an evolutionary perspective, given that it has ultimately evolved from a symmetrical ancestor. Here, we use artificial selection to test the hypothesis that anti-symmetry can evolve through the genetic assimilation of a developmental error that occurs in the production of an environmentally cued threshold trait. We find that anti-symmetry in the legs of the acarid mite, Rhizoglyphus echinopus, is heritable and that we are able to increase the frequency of the anti-symmetrical males through artificial selection. We find no evidence that the developmental instability of anti-symmetrical males is associated with negative fitness consequences in terms of larval viability and inbreeding depression. Our study provides empirical support for the notion that developmental errors in the production of threshold traits can be the genesis for the subsequent genetic assimilation of the phenotypic novelty that is broken symmetry.

opencc-zeroOct 2020View details →

Selection on phenotypic plasticity favors thermal canalization

Climate change affects organisms worldwide with profound ecological and evolutionary consequences, often increasing population extinction risk. Climatic factors can increase the strength, variability or direction of natural selection on phenotypic traits, potentially driving adaptive evolution. Phenotypic plasticity in relation to temperature can allow organisms to maintain fitness in response to increasing temperatures, thereby "buying time" for subsequent genetic adaptation and promoting evolutionary rescue. Although many studies have shown that organisms respond plastically to increasing temperatures, it is unclear if such thermal plasticity is adaptive. Moreover, we know little about how natural and sexual selection operate on thermal reaction norms reflecting such plasticity. Here, we investigate how natural and sexual selection shape phenotypic plasticity in two congeneric and phenotypically similar sympatric insect species. We show that the thermal optima for longevity and mating success differ, suggesting temperature-dependent trade-offs between survival and reproduction in both sexes. Males in these species have similar thermal reaction norm slopes but have diverged in baseline body temperature (intercepts), being higher for the more northern species. Natural selection favoured reduced thermal reaction norm slopes at high ambient temperatures, suggesting that the current level of thermal plasticity is maladaptive in the context of anthropogenic climate change and that selection now promotes thermal canalization and robustness. Our results show that ectothermic animals also at high latitudes can suffer from overheating and challenge the common view of phenotypic plasticity as being beneficial in harsh and novel environments.

opencc-zeroSep 2021View details →

Data belonging to: Lining the nest with more feathers increases offspring recruitment probability: Selection on an extended phenotype in the blue tit

Birds, among various other taxa, construct nests. Nests form an extended phenotype of the individual building it. Nests are used to extend control over the conditions in which offspring develop, and are therefore commonly considered to be shaped by selection. Nevertheless, scarcely any scientific evidence exist that nest composition is under selection. Here, we demonstrate with data from over 400 blue tit (Cyanistes caeruleus) nests collected over eight years that a higher proportion of feathers in the nest lining is positively associated with the probability of offspring to recruit as a breeding adult later in life. Strikingly, the extended phenotype (nest) was associated stronger with recruitment probability than phenotypic traits that have typically been considered important in selection (laying date, and female size and condition). Our findings suggest that the choice of nest material could be a maternal behaviour with potential lifelong effects on her offspring.

opencc-by-4.0Nov 2020View details →

Data and statistical analysis scripts for manuscript on high-throughput phenotyping of root economics in wheat

This repository contains the root data, GEMMA files, and R code for generating the statistics and figures used in a preprint describing high-throughput phenotyping of root respiration in winter wheat. Functional phenomics and genetics of the root economics space in winter wheat using high-throughput phenotyping of respiration and architecture Haichao Guo, Habtamu Ayalew, Anand Seethepalli, Kundan Dhakal, Marcus Griffiths, Xue-Feng Ma, Larry M. York bioRxiv 2020.11.12.380238; doi: <a href="https://doi.org/10.1101/2020.11.12.380238">https://doi.org/10.1101/2020.11.12.380238</a> analysis.R - A script for processing the included 4 CSV files of collected data. It is intended to run directly in RStudio and will automatically set the working directory in that case. The GEMMA folder includes files as output from GEMMA for genetic analysis, as described in the methods section of the preprint. These files are required by the R code for making Manhattan plots and other output. It will automatically create an output folder and the output text and figure files. The protocol for the respiration measurements are available in a separate Zenodo repository: <a href="https://doi.org/10.5281/zenodo.4247873">https://doi.org/10.5281/zenodo.4247873</a> Please cite this repository and the preprint if any data or R code is used in your work.

opencc-by-4.0Nov 2020View details →

Protocol and data analysis scripts for high-throughput phenotyping of specific root respiration

This repository contains a PDF written protocol with figures describing a method for measuring root respiration using an infrared gas analyzer (LI-850) and the R script necessary for processing the text files to derive CO2 flux. Just download the ZIP file, unzip locally, open either the PDF or the .R file. root_respiration_protocol.pdf - The illustrated protocol includes instruments and parts needed. root_respiration_script.R - A script for processing the included 15 .txt files as examples from a LI-850 Gas Analyzer and extract absolute CO2 flux with example code for how to incorporate root mass or length to derive specific root respiration. It is intended to run directly in RStudio and will automatically set the working directory in that case. Please cite this repository if the protocol or R script is used in your work.  Guo, H., Ayalew, H., Seethepalli, A., Dhakal, K., Griffiths, M., Ma, X., York, L. M. (2020). Protocol and data analysis scripts for high-throughput phenotyping of specific root respiration [Data set]. Zenodo. http://doi.org/10.5281/zenodo.4247873 The first manuscript using and describing this method is available: Guo, H., Ayalew, H., Seethepalli, A., Dhakal, K., Griffiths, M., Ma, X., York, L. M. (2021). Functional phenomics and genetics of the root economics space in winter wheat using high-throughput phenotyping of respiration and architecture. <a href="https://nph.onlinelibrary.wiley.com/doi/10.1111/nph.17329">New Phytologist. DOI: 10.1111/nph.17329</a>

opencc-by-nd-4.0Nov 2020View details →

The impact of phenotypic heterogeneity of tumour cells on treatment and relapse dynamics - Dataset

This is the dataset used in the manuscript "The impact of phenotypic heterogeneity of tumour cells on treatment and relapse dynamics" by Raatz et al. The code used to generate the data and figures can be found at https://doi.org/10.5281/zenodo.4461667.

Natural history, phenotypic spectrum, and discriminative features of multisystemic RFC1-disease

Objective: To delineate the full phenotypic spectrum, discriminative features, piloting longitudinal progression data, and sample size calculations of RFC1-repeat expansions, recently identified as causing cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). Methods: Multimodal RFC1 repeat screening (PCR, southern blot, whole-exome/genome (WES/WGS)-based approaches) combined with cross-sectional and longitudinal deep-phenotyping in (i) cross-European cohort A (70 families) with ≥2 features of CANVAS and/or ataxia-with-chronic-cough (ACC); and (ii) Turkish cohort B (105 families) with unselected late-onset ataxia. Results: Prevalence of RFC1-disease was 67% in cohort A, 14% in unselected cohort B, 68% in clinical CANVAS, and 100% in ACC. RFC1-disease was also identified in Western and Eastern Asians, and even by WES. Visual compensation, sensory symptoms, and cough were strong positive discriminative predictors (>90%) against RFC1-negative patients. The phenotype across 70 RFC1-positive patients was mostly multisystemic (69%), including dysautonomia (62%) and bradykinesia (28%) (=overlap with cerebellar-type multiple system atrophy [MSA-C]), postural instability (49%), slow vertical saccades (17%), and chorea and/or dystonia (11%). Ataxia progression was ~1.3 SARA points/year (32 cross-sectional, 17 longitudinal assessments, follow-up ≤9 years [mean 3.1]), but also included early falls, variable non-linear phases of MSA-C-like progression (SARA 2.5-5.5/year), and premature death. Treatment trials require 330 (1-year-trial) and 132 (2-year-trial) patients in total to detect 50% reduced progression. Conclusions: RFC1-disease is frequent and occurs across continents, with CANVAS and ACC as highly diagnostic phenotypes, yet as variable, overlapping clusters along a continuous multisystemic disease spectrum, including MSA-C-overlap. Our natural history data help to inform future RFC1-treatment trials.

Cis-regulatory variation in the shavenbaby gene underlies intraspecific phenotypic variation, mirroring interspecific divergence in the same trait

Despite considerable progress in recent decades in dissecting the genetic causes of natural morphological variation, there is limited understanding of how variation within species ultimately contributes to species differences. We have studied patterning of the non-sensory hairs, commonly known as "trichomes," on the dorsal cuticle of first-instar larvae of Drosophila. Most Drosophila species produce a dense lawn of trichomes, but a subset of dorsal trichomes were lost in D. sechellia and D. ezoana due entirely to regulatory evolution of the shavenbaby (svb) gene. Here we describe intraspecific variation in dorsal trichome patterns of first-instar larvae of D. virilis that is similar to the trichome pattern variation identified previously between species. We found that 67% of this difference is explained by a QTL that contains svb and that svb expression correlates with trichome variation within D. virilis . Despite using an experimental design with reasonable power to detect a second locus accounting for the remainder of the variance in trichome number, only a single QTL could be mapped, suggesting that multiple other loci each make a small contribution to trichome patterning. Thus, the genetic architecture of intraspecific variation and interspecific differences exhibit similarities and differences that may reflect differences between short-term and long-term evolutionary processes.

Phenotype pictures of Arabidopsis thaliana in high light and low light conditions

The rate at which plants grow is a major functional trait in plant ecology. However, little is known about its evolution in natural populations. Here, we investigate evolutionary and environmental factors shaping variation in the growth rate of Arabidopsis thaliana. We used plant diameter as a proxy to monitor plant growth over time in environments that mimicked latitudinal differences in the intensity of natural light radiation, across a set of 278 genotypes sampled within four broad regions, including an outgroup set of genotypes from China. The observed variation was validated in a field experiment conducted under natural conditions. All genotypes grew markedly wider rosettes when the light supply was decreased, demonstrating that environmental plasticity is a predominant source of variation to adapt plant size to prevailing light conditions. Yet, we detected significant levels of genetic variation both in growth rate and growth plasticity. Genome-wide association studies revealed that only 2 single nucleotide polymorphisms associate with genetic variation for growth above Bonferroni confidence levels. However, marginally associated variants were strongly enriched among genes with an annotated role in growth and stress reactions. Polygenic scores computed from marginally associated variants confirmed the polygenic basis of growth variation. For both light regimes, phenotypic divergence between Europe and the distantly related populations of China is smaller than the variation observed within Europe indicating that plant growth is constrained by stabilizing selection. We observed that Spanish genotypes, however, reach a significantly larger size than Northern European genotypes. Tests of adaptive divergence and analysis of the individual burden of deleterious mutations reveal that adaptive processes have played a more important role in shaping regional differences in rosette growth than maladaptive evolution.

Life history evolution, species differences and phenotypic plasticity in hemiparasitic eyebrights (Euphrasia)

Premise of the study: Species delimitation in parasitic organisms is challenging as traits used in the identification of species are often plastic and vary depending on the host. Here, we use species from a recent radiation of generalist hemiparasitic Euphrasia to investigate trait variation and trait plasticity. We test whether Euphrasia species show reliable trait differences, investigate whether these differences correspond to life history trade-offs between growth and reproduction, and quantify plasticity in response to host species. Methods: We perform common garden experiments to evaluate trait differences between eleven Euphrasia taxa grown on a common host, document phenotypic plasticity when a single Euphrasia species is grown on eight different hosts, and relate our observations to trait differences recorded in the wild. Key results: Euphrasia exhibit variation in life history strategies; some individuals transition rapidly to flower at the expense of early season growth, while others invest in vegetative growth and delay flowering. Life history differences are present between some species, though many related taxa lack clear-cut trait differences. Species differences are further blurred by phenotypic plasticity—many traits are plastic and change with host type or between environments. Conclusions: Phenotypic plasticity in response to host and environment confounds species delimitation in Euphrasia. When grown in a common garden environment it is possible to identify some morphologically distinct taxa, though others represent morphologically similar shallow segregates. Trait differences present between some species and populations demonstrates the rapid evolution of distinct life history strategies in response to local ecological conditions.

Extensive hybridization reveals multiple coloration genes underlying a complex plumage phenotype

Coloration is an important target of both natural and sexual selection. Discovering the genetic basis of colour differences can help us to understand how this visually striking phenotype evolves. Hybridizing taxa with both clear colour differences and shallow genomic divergences are unusually tractable for associating coloration phenotypes with their causal genotypes. Here, we leverage the extensive admixture between two common North American woodpeckers—yellow-shafted and red-shafted flickers—to identify the genomic bases of six distinct plumage patches involving both melanin and carotenoid pigments. Comparisons between flickers across ~7.25 million genome-wide SNPs show that these two forms differ at only a small proportion of the genome (mean FST = 0.008). Within the few highly differentiated genomic regions, we identify 368 SNPs significantly associated with four of the six plumage patches. These SNPs are linked to multiple genes known to be involved in melanin and carotenoid pigmentation. For example, a gene (CYP2J19) known to cause yellow to red colour transitions in other birds is strongly associated with the yellow versus red differences in the wings and tail feathers of these flickers. Additionally, our analyses suggest novel links between known melanin genes and carotenoid coloration. Our finding of patch-specific control of plumage coloration adds to the growing body of literature suggesting colour diversity in animals could be created through selection acting on novel combinations of coloration genes.

FIGURE 4 in Phenotypic divergence in large sized cricket frog species that crossed the geographical barriers within peninsular India

FIGURE 4. Principal Component Analysis for male individuals of F. kalinga (from WG and EG), F. goemchi and F. kudremukhensis using six morphometric characters (Table 2) transformed to their ratio to SVL for from the Western Ghats.

FIGURE 3. Principal Component Analysis for male individuals using 31 in Phenotypic divergence in large sized cricket frog species that crossed the geographical barriers within peninsular India

FIGURE 3. Principal Component Analysis for male individuals using 31 morphometric characters (Table 1) transformed to their ratio to SVL for F. kalinga from the Eastern Ghats and the Western Ghats.

FIGURE 2 in Phenotypic divergence in large sized cricket frog species that crossed the geographical barriers within peninsular India

FIGURE 2. Maximum Likelihood phylogeny for the large sized fejervaryan frogs having predominant distribution in the Western Ghats / Eastern Ghats' (Figure 2, Phuge et al. 2019) with the present data based on 529 bp of mitochondrial 16S rRNA gene.

FIGURE 1 in Phenotypic divergence in large sized cricket frog species that crossed the geographical barriers within peninsular India

FIGURE 1. Details of the type localities for the species of Fejervarya described from peninsular India (1. F. orissaensis; 2. F. kalinga (from the Eastern Ghats, marked by a star); 3. F. marathi; 4. F. syhadrensis; 5. F. cepfi; 6. F. goemchi; 7. F. gomantaki; 8. New collections of F. kalinga from the Western Ghats (marked by a star); 9. F. krishnan; 10. F. modesta; 11. F. mysorensis;12. F. kudremukhensis; 13. F. sahyadris; 14. F. rufescens; 15.F. sauriceps;16. F. caperata; 17. F. mudduraja; 18. F. murthii; 19. F. nilagirica; 20. F. neilcoxi; 21. F. kadar; 22. F. parambikulamana; 23. F. keralensis; 24. F. manoharani and 25. F. agricola;)

Phenotypic integration in feliform carnivores: covariation patterns and disparity in hypercarnivores versus generalists

The skeleton is a complex arrangement of anatomical structures that covary to various degrees depending on both intrinsic and extrinsic factors. Among the Feliformia, many species are characterized by predator lifestyles providing a unique opportunity to investigate the impact of highly specialised hypercarnivorous diet on phenotypic integration and shape diversity. To do so, we compared the shape of the skull, mandible, humerus, and femur of species in relation to their feeding strategies (hypercarnivorous versus generalist species) and prey preference (predators of small versus large prey) using three-dimensional geometric morphometric techniques. Our results highlight different degrees of morphological integration in the Feliformia depending on the functional implication of the anatomical structure, with an overall higher covariation of structures in hypercarnivorous species. The skull and the forelimb are not integrated in generalist species whereas they are in hypercarnivores. These results can potentially be explained by the different feeding strategies of these species. Contrary to our expectations, hypercarnivores display a higher disparity for the skull than generalist species. This is probably due to the fact that a specialisation toward high-meat diet could be achieved through various phenotypes. Finally, humeri and femora display shape variations depending on relative prey size preference. Large species feeding on large prey tend to have robust long bones due to higher biomechanical constraints.

opencc-zeroJan 2021View details →

Metabolic rate shapes phenotypic covariance among physiological, behavioral, and life history traits in honeybees

Metabolic rate is often cited as the fundamental rate that determines the rate of all biological processes by shaping energetic availability for the various behavioral and life history traits that contribute to performance. It has therefore been suggested that metabolic rate drives the widely observed covariance among these different levels of phenotypic traits. However, much of the work on this topic has relied on pairwise correlational analysis, thereby leaving an important gap in our understanding regarding the functional links that shape this phenotypic covariance, often referred to as pace-of-life. Using honeybees as an experimental model, we measured a large number of behavioral, life history and physiological traits in individual bees and used a structural equation model to characterize the phenotypic covariance structure among these traits. Following this with a path analysis, we demonstrate that variation in metabolic rate plays a fundamental proximate role in driving this phenotypic covariance structure in honeybees. We discuss the importance of these findings in the context of how interindividual variation in terms of slow-fast phenotypes may drive the phenotype of a group and the functional role metabolic rate might play in shaping division of labor and social evolution.

opencc-zeroJan 2021View details →

Diet variation driven by color vision phenotype in wild capuchin monkeys

The polymorphic color vision of platyrrhine monkeys is a fascinating example of balancing selection acting on multiple genetic and phenotypic morphs. Yet, the mechanism of natural selection maintaining this variation remains elusive. Past research has demonstrated task-specific foraging advantages to dichromatic (two-opsin vision, red-green colorblind) and trichromatic (three-opsin vision, human "normal") monkeys, raising the potential for dietary niche differentiation. We ask whether color vision type influences diet variation in a population of wild, white-faced capuchins (Cebus imitator) in Costa Rica. To assess this, we record food intake during simultaneous focal follows of adult female dichromats and trichromats, and classify the conspicuity of diet items in capuchin visual space. We assess the degree of dietary and nutritional niche overlap during periods of high and low fruit abundance using nutritional geometry and Pianka's index. We find that in months of high fruit abundance, trichromats have higher intake of conspicuously-colored fruits, while dichromats have higher intake of camouflaged invertebrates, resulting in lower niche overlap. These differences disappear in months of low habitat-wide fruit abundance, a time when overall dietary breadth collapses. Our results support the hypothesis that niche differentiation in diet contributes to maintaining color vision variation without compromising species-specific nutritional intake.