scholarly journals Minimally invasive brain injections for viral-mediated transgenesis: New tools for behavioral genetics in sticklebacks

2020 ◽  
Author(s):  
Noelle James ◽  
Alison Bell
Keyword(s):  
Minimally Invasive ◽  
Gasterosteus Aculeatus ◽  
Behavioral Genetics ◽  
Natural Populations ◽  
Model Organisms ◽  
Neurosurgical Procedure ◽  
Behavioral Traits ◽  
Genomic Tools ◽  
Genetic Mechanisms ◽  
Technological Limitations

AbstractBehavioral genetics in non-model organisms is currently gated by technological limitations. However, with the growing availability of genome editing and functional genomic tools, complex behavioral traits such as social behavior can now be explored in diverse organisms. Here we present a minimally invasive neurosurgical procedure for a classic behavioral, ecological and evolutionary system: threespine stickleback (Gasterosteus aculeatus). This method of direct brain injection enables viral-mediated transgenesis and pharmaceutical delivery which bypasses the blood-brain barrier. This method is flexible, fast, and amenable to statistically powerful within-subject experimental designs, making it well-suited for use in genetically diverse animals such as those collected from natural populations.Viral-mediated transgenesis in the brain allows for a direct examination of the genetic mechanisms underlying behavior in wild-caught animals from natural populations. Using this method, we were able to detect changes in aggression from the knockdown of either of two different genes, arginine vasopressin (AVP) and monoamine oxidase (MAOA), in outbred animals in less than one month. In addition, we demonstrate that widely available mammalian plasmids work with this method, lowering the barrier of entry to the technique.

scholarly journals Minimally invasive brain injections for viral-mediated transgenesis: New tools for behavioral genetics in sticklebacks

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251653
Author(s):  
Noelle James ◽  
Alison Bell
Keyword(s):  
Minimally Invasive ◽  
Repeated Measures ◽  
Gasterosteus Aculeatus ◽  
Behavioral Genetics ◽  
Expression Profiles ◽  
Survival Rates ◽  
Natural Populations ◽  
Failure To Thrive ◽  
Warning Signs ◽  
Model Organisms

Behavioral genetics in non-model organisms is currently gated by technological limitations. However, with the growing availability of genome editing and functional genomic tools, complex behavioral traits such as social behavior can now be explored in diverse organisms. Here we present a minimally invasive neurosurgical procedure for a classic behavioral, ecological and evolutionary system: threespine stickleback (Gasterosteus aculeatus). Direct brain injection enables viral-mediated transgenesis and pharmaceutical delivery which bypasses the blood-brain barrier. This method is flexible, fast, and amenable to statistically powerful within-subject experimental designs, making it well-suited for use in genetically diverse animals such as those collected from natural populations. Developing this minimally invasive neurosurgical protocol required 1) refining the anesthesia process, 2) building a custom surgical rig, and 3) determining the normal recovery pattern allowing us to clearly identify warning signs of failure to thrive. Our custom-built surgical rig (publicly available) and optimized anesthetization methods resulted in high (90%) survival rates and quick behavioral recovery. Using this method, we detected changes in aggression from the overexpression of either of two different genes, arginine vasopressin (AVP) and monoamine oxidase (MAOA), in outbred animals in less than one month. We successfully used multiple promoters to drive expression, allowing for tailored expression profiles through time. In addition, we demonstrate that widely available mammalian plasmids work with this method, lowering the barrier of entry to the technique. By using repeated measures of behavior on the same fish before and after transfection, we were able to drastically reduce the necessary sample size needed to detect significant changes in behavior, making this a viable approach for examining genetic mechanisms underlying complex social behaviors.

Genetics and Psychology: Beyond Heritability

2001 ◽  
Vol 6 (4) ◽  
pp. 229-240 ◽  
Author(s):  
Robert Plomin ◽  
Essi Colledge
Keyword(s):  
Individual Differences ◽  
Genetic Factors ◽  
Behavioral Genetics ◽  
Genetic Research ◽  
Genetic Influences ◽  
Behavioral Traits ◽  
Nonshared Environment ◽  
Genetic Mechanisms ◽  
Asking Questions ◽  
Psychological Dimensions

The questions whether and how much genetic factors affect psychological dimensions and disorders represent important first steps in understanding the origins of individual differences. Because it is now widely accepted that genetic influences contribute importantly to individual differences throughout psychology, genetic research is moving beyond merely estimating heritability to asking questions about how genetic mechanisms work. We focus on two examples of ways in which genetic research is going beyond heritability. The first is to use genetically sensitive designs to identify specific environmental influences, taking into account two of the most important findings from behavioral genetics: nonshared environment and genotype-environment correlation. The second is to use the new tools of molecular genetics to identify specific genes responsible for the substantial heritability of a variety of behavioral traits.

scholarly journals Impact of citronellol on river and soil environments using non-target model organisms and natural populations

2021 ◽  
Vol 287 ◽  
pp. 112303
Author(s):  
María Rosa Pino-Otín ◽  
Elisa Langa ◽  
Jonatan Val ◽  
Ana M. Mainar ◽  
Diego Ballestero
Keyword(s):  
Natural Populations ◽  
Model Organisms ◽  
Target Model

scholarly journals Heritability of DNA methylation in threespine stickleback (Gasterosteus aculeatus)

Genetics ◽  
2021 ◽  
Vol 217 (1) ◽  
Author(s):  
Juntao Hu ◽  
Sara J S Wuitchik ◽  
Tegan N Barry ◽  
Heather A Jamniczky ◽  
Sean M Rogers ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genetic Architecture ◽  
Gasterosteus Aculeatus ◽  
Additive Genetic Variance ◽  
Natural Populations ◽  
Threespine Stickleback ◽  
Phenotypic Change ◽  
Cpg Sites ◽  
Cis And Trans ◽  
Methylation Variation

Abstract Epigenetic mechanisms underlying phenotypic change are hypothesized to contribute to population persistence and adaptation in the face of environmental change. To date, few studies have explored the heritability of intergenerationally stable methylation levels in natural populations, and little is known about the relative contribution of cis- and trans-regulatory changes to methylation variation. Here, we explore the heritability of DNA methylation, and conduct methylation quantitative trait loci (meQTLs) analysis to investigate the genetic architecture underlying methylation variation between marine and freshwater ecotypes of threespine stickleback (Gasterosteus aculeatus). We quantitatively measured genome-wide DNA methylation in fin tissue using reduced representation bisulfite sequencing of F1 and F2 crosses, and their marine and freshwater source populations. We identified cytosines (CpG sites) that exhibited stable methylation levels across generations. We found that additive genetic variance explained an average of 24–35% of the methylation variance, with a number of CpG sites possibly autonomous from genetic control. We also detected both cis- and trans-meQTLs, with only trans-meQTLs overlapping with previously identified genomic regions of high differentiation between marine and freshwater ecotypes. Finally, we identified the genetic architecture underlying two key CpG sites that were differentially methylated between ecotypes. These findings demonstrate a potential role for DNA methylation in facilitating adaptation to divergent environments and improve our understanding of the heritable basis of population epigenomic variation.

Evolution of stickleback spines through independent cis-regulatory changes at HOXDB

2021 ◽  
Author(s):  
Julia I Wucherpfennig ◽  
Timothy R Howes ◽  
Jessica N Au ◽  
Eric H Au ◽  
Garrett A Roberts Kingman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Evolutionary Biology ◽  
Gasterosteus Aculeatus ◽  
Molecular Mechanisms ◽  
Wild Populations ◽  
Gene Variation ◽  
Regulatory Changes ◽  
Fundamental Goal ◽  
Apeltes Quadracus ◽  
Genetic Mechanisms

Understanding the genetic mechanisms leading to new traits is a fundamental goal of evolutionary biology. We show that HOXDB regulatory changes have been used repeatedly in different stickleback fish species to alter the length and number of bony dorsal spines. In Gasterosteus aculeatus, a variant HOXDB allele is genetically linked to shortening an existing spine and adding a spine. In Apeltes quadracus, a variant allele is associated with lengthening an existing spine and adding a spine. The alleles alter the same conserved non-coding HOXDB enhancer by diverse molecular mechanisms, including SNPs, deletions, and transposable element insertions. The independent cis-acting regulatory changes are linked to anterior expansion or contraction of HOXDB expression. Our findings support the long-standing hypothesis that natural Hox gene variation underlies key morphological patterning changes in wild populations and illustrate how different mutational mechanisms affecting the same region may produce opposite gene expression changes with similar phenotypic outcomes.

scholarly journals Two different epigenetic pathways detected in wild three-spined sticklebacks are involved in salinity adaptation

2019 ◽  
Author(s):  
Melanie J. Heckwolf ◽  
Britta S. Meyer ◽  
Robert Häsler ◽  
Marc P. Höppner ◽  
Christophe Eizaguirre ◽  
...  
Keyword(s):  
Natural Selection ◽  
Gasterosteus Aculeatus ◽  
Natural Populations ◽  
Wild Populations ◽  
Epigenetic Marks ◽  
Transgenerational Plasticity ◽  
The Face ◽  
Adaptation Processes ◽  
Methylation Patterns ◽  
Rapid Emergence

AbstractWhile environmentally inducible epigenetic marks are discussed as one mechanism of transgenerational plasticity, environmentally stable epigenetic marks emerge randomly. When resulting in variable phenotypes, stable marks can be targets of natural selection analogous to DNA sequence-based adaptation processes. We studied both postulated pathways in natural populations of three-spined sticklebacks (Gasterosteus aculeatus) and sequenced their methylomes and genomes across a salinity cline. Consistent with local adaptation, populations showed differential methylation (pop-DMS) at genes enriched for osmoregulatory processes. In a two-generation experiment, 62% of these pop-DMS were insensitive to salinity manipulation, suggesting that they could be stable targets for natural selection. Two-thirds of the remaining inducible pop-DMS became more similar to patterns detected in wild populations from the corresponding salinity, and this pattern accentuated over consecutive generations, indicating a mechanism of adaptive transgenerational plasticity. Natural DNA methylation patterns can thus be attributed to two epigenetic pathways underlying the rapid emergence of adaptive phenotypes in the face of environmental change.

scholarly journals Persistent and plastic effects of temperature on DNA methylation across the genome of threespine stickleback ( Gasterosteus aculeatus )

2017 ◽  
Vol 284 (1864) ◽  
pp. 20171667 ◽  
Author(s):  
David C. H. Metzger ◽  
Patricia M. Schulte
Keyword(s):  
Dna Methylation ◽  
Time Scales ◽  
Gasterosteus Aculeatus ◽  
Natural Populations ◽  
Thermal Response ◽  
Thermal Acclimation ◽  
Threespine Stickleback ◽  
Multiple Time Scales ◽  
Acclimation Temperature ◽  
Multiple Time

Epigenetic mechanisms such as changes in DNA methylation have the potential to affect the resilience of species to climate change, but little is known about the response of the methylome to changes in environmental temperature in animals. Using reduced representation bisulfite sequencing, we assessed the effects of development temperature and adult acclimation temperature on DNA methylation levels in threespine stickleback ( Gasterosteus aculeatus ). Across all treatments, we identified 2130 differentially methylated cytosines distributed across the genome. Both increases and decreases in temperature during development and with thermal acclimation in adults increased global DNA methylation levels. Approximately 25% of the differentially methylated regions (DMRs) responded to both developmental temperature and adult thermal acclimation, and 50 DMRs were common to all treatments, demonstrating a core response of the epigenome to thermal change at multiple time scales. We also identified differentially methylated loci that were specific to a particular developmental or adult thermal response, which could facilitate the accumulation of epigenetic variation between natural populations that experience different thermal regimes. These data demonstrate that thermal history can have long-lasting effects on the epigenome, highlighting the role of epigenetic modifications in the response to temperature change across multiple time scales.

scholarly journals A Killer–Rescue system for self-limiting gene drive of anti-pathogen constructs

2008 ◽  
Vol 275 (1653) ◽  
pp. 2823-2829 ◽  
Author(s):  
Fred Gould ◽  
Yunxin Huang ◽  
Mathieu Legros ◽  
Alun L Lloyd
Keyword(s):  
Gene Action ◽  
Natural Populations ◽  
Gene Drive ◽  
Fitness Costs ◽  
Molecular Approaches ◽  
Genetic Mechanisms ◽  
Rescue System ◽  
Near Term ◽  
Killer Gene ◽  
Over Time

A number of genetic mechanisms have been suggested for driving anti-pathogen genes into natural populations. Each of these mechanisms requires complex genetic engineering, and most are theoretically expected to permanently spread throughout the target species' geographical range. In the near term, risk issues and technical limits of molecular methods could delay the development and use of these mechanisms. We propose a gene-drive mechanism that can be self-limiting over time and space, and is simpler to build. This mechanism involves one gene that codes for toxicity (killer) and a second that confers immunity to the toxic effects (rescue). We use population-genetic models to explore cases with one or two independent insertions of the killer gene and one insertion of the rescue gene. We vary the dominance and penetrance of gene action, as well as the magnitude of fitness costs. Even with the fitness costs of 10 per cent for each gene, the proportion of mosquitoes expected to transmit the pathogen decreases below 5 per cent for over 40 generations after one 2 : 1 release (engineered : wild) or after four 1 : 2 releases. Both the killer and rescue genes will be lost from the population over time, if the rescue construct has any associated fitness cost. Molecular approaches for constructing strains are discussed.

scholarly journals Rapid evolution of cold tolerance in stickleback

2010 ◽  
Vol 278 (1703) ◽  
pp. 233-238 ◽  
Author(s):  
Rowan D. H. Barrett ◽  
Antoine Paccard ◽  
Timothy M. Healy ◽  
Sara Bergek ◽  
Patricia M. Schulte ◽  
...  
Keyword(s):  
Cold Tolerance ◽  
Gasterosteus Aculeatus ◽  
Field Experiments ◽  
Rapid Evolution ◽  
Natural Populations ◽  
Temperature Tolerance ◽  
Ancestral Population ◽  
Biological Communities ◽  
Evolutionary Consequences ◽  
Short Time

Climate change is predicted to lead to increased average temperatures and greater intensity and frequency of high and low temperature extremes, but the evolutionary consequences for biological communities are not well understood. Studies of adaptive evolution of temperature tolerance have typically involved correlative analyses of natural populations or artificial selection experiments in the laboratory. Field experiments are required to provide estimates of the timing and strength of natural selection, enhance understanding of the genetics of adaptation and yield insights into the mechanisms driving evolutionary change. Here, we report the experimental evolution of cold tolerance in natural populations of threespine stickleback fish ( Gasterosteus aculeatus ). We show that freshwater sticklebacks are able to tolerate lower minimum temperatures than marine sticklebacks and that this difference is heritable. We transplanted marine sticklebacks to freshwater ponds and measured the rate of evolution after three generations in this environment. Cold tolerance evolved at a rate of 0.63 haldanes to a value 2.5°C lower than that of the ancestral population, matching values found in wild freshwater populations. Our results suggest that cold tolerance is under strong selection and that marine sticklebacks carry sufficient genetic variation to adapt to changes in temperature over remarkably short time scales.

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