scholarly journals Drosophila simulans: A Species with Improved Resolution in Evolve and Resequence Studies

2017 ◽  
Vol 7 (7) ◽  
pp. 2337-2343 ◽  
Author(s):  
Neda Barghi ◽  
Raymond Tobler ◽  
Viola Nolte ◽  
Christian Schlötterer
Keyword(s):  
Genetic Variation ◽  
Experimental Evolution ◽  
Genetic Variants ◽  
Adaptive Response ◽  
Complex Traits ◽  
High Throughput Sequencing ◽  
Candidate Snps ◽  
Recombination Rates ◽  
Hot Environment ◽  
Powerful Approach

Abstract The combination of experimental evolution with high-throughput sequencing of pooled individuals—i.e., evolve and resequence (E&R)—is a powerful approach to study adaptation from standing genetic variation under controlled, replicated conditions. Nevertheless, E&R studies in Drosophila melanogaster have frequently resulted in inordinate numbers of candidate SNPs, particularly for complex traits. Here, we contrast the genomic signature of adaptation following ∼60 generations in a novel hot environment for D. melanogaster and D. simulans. For D. simulans, the regions carrying putatively selected loci were far more distinct, and thus harbored fewer false positives, than those in D. melanogaster. We propose that species without segregating inversions and higher recombination rates, such as D. simulans, are better suited for E&R studies that aim to characterize the genetic variants underlying the adaptive response.

scholarly journals Crossing design shapes patterns of genetic variation in synthetic recombinant populations of Saccharomyces cerevisiae

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mark A. Phillips ◽  
Ian C. Kutch ◽  
Kaitlin M. McHugh ◽  
Savannah K. Taggard ◽  
Molly K. Burke
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Genetic Variation ◽  
Experimental Evolution ◽  
Complex Traits ◽  
Inbred Lines ◽  
Equal Proportion ◽  
Adaptive Potential ◽  
Synthetic Populations ◽  
The Impact ◽  
Isogenic Strains

Abstract“Synthetic recombinant” populations have emerged as a useful tool for dissecting the genetics of complex traits. They can be used to derive inbred lines for fine QTL mapping, or the populations themselves can be sampled for experimental evolution. In the latter application, investigators generally value maximizing genetic variation in constructed populations. This is because in evolution experiments initiated from such populations, adaptation is primarily fueled by standing genetic variation. Despite this reality, little has been done to systematically evaluate how different methods of constructing synthetic populations shape initial patterns of variation. Here we seek to address this issue by comparing outcomes in synthetic recombinant Saccharomyces cerevisiae populations created using one of two strategies: pairwise crossing of isogenic strains or simple mixing of strains in equal proportion. We also explore the impact of the varying the number of parental strains. We find that more genetic variation is initially present and maintained when population construction includes a round of pairwise crossing. As perhaps expected, we also observe that increasing the number of parental strains typically increases genetic diversity. In summary, we suggest that when constructing populations for use in evolution experiments, simply mixing founder strains in equal proportion may limit the adaptive potential.

scholarly journals Core gene identification using gene expression

2020 ◽  
Author(s):  
◽  
Annique Claringbould
Keyword(s):  
Gene Expression ◽  
Genetic Variation ◽  
Genetic Code ◽  
Genetic Variants ◽  
Complex Traits ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Altered Level ◽  
Common Genetic Variants

While humans share most of their genetic code with one another, small differences in the DNA can have an impact on an individual’s risk of disease. Common genetic variants exert individually small effects on the development of a disease, but their combined impact is substantial. Although recent research has identified thousands of variants that are associated to complex traits, our understanding of the molecular mechanisms that eventually lead to disease is limited. One way to dive into the molecular changes that result from genetic variation, is to look at changes in gene activity (‘gene expression’). Each cell contains the same genetic code, but genes are only expressed when and where they are required. Research has shown that many disease-associated genetic variants also affect gene expression. Such a change in the expression of a gene can lead to an altered level of the protein it encodes, which in turn can be the start of a dysregulation in the system that can eventually develop into a disease. This thesis describes how gene expression patterns can be used to prioritise and describe the function of trait-relevant genes. The first chapters evaluate methodological considerations for doing gene expression research. Another study covers the systematic linking of genetic variation to gene expression in blood and the last research chapter describes a method for gene prioritisation that leverages the idea that multiple genetic variants converge onto disease-causing genes. These insights can be used to better understand disease and to identify potential drug targets.

scholarly journals Impact of rare and common genetic variation in the interleukin-1 pathway on human cytokine responses

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Rosanne C. van Deuren ◽  
Peer Arts ◽  
Giulio Cavalli ◽  
Martin Jaeger ◽  
Marloes Steehouwer ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Genetic Variants ◽  
Complex Traits ◽  
Rare Variants ◽  
Interleukin 1 ◽  
Healthy Individuals ◽  
Cytokine Responses ◽  
Common Genetic Variants ◽  
Bidirectional Association

Abstract Background The interleukin (IL)-1 pathway is primarily associated with innate immunological defense and plays a major role in the induction and regulation of inflammation. Both common and rare genetic variation in this pathway underlies various inflammation-mediated diseases, but the role of rare variants relative to common variants in immune response variability in healthy individuals remains unclear. Methods We performed molecular inversion probe sequencing on 48 IL-1 pathway-related genes in 463 healthy individuals from the Human Functional Genomics Project. We functionally grouped common and rare variants, over gene, subpathway, and inflammatory levels and performed the Sequence Kernel Association Test to test for association with in vitro stimulation-induced cytokine responses; specifically, IL-1β and IL-6 cytokine measurements upon stimulations that represent an array of microbial infections: lipopolysaccharide (LPS), phytohaemagglutinin (PHA), Candida albicans (C. albicans), and Staphylococcus aureus (S. aureus). Results We identified a burden of NCF4 rare variants with PHA-induced IL-6 cytokine and showed that the respective carriers are in the 1% lowest IL-6 producers. Collapsing rare variants in IL-1 subpathway genes produces a bidirectional association with LPS-induced IL-1β cytokine levels, which is reflected by a significant Spearman correlation. On the inflammatory level, we identified a burden of rare variants in genes encoding for proteins with an anti-inflammatory function with S. aureus-induced IL-6 cytokine. In contrast to these rare variant findings which were based on different types of stimuli, common variant associations were exclusively identified with C. albicans-induced cytokine over various levels of grouping, from the gene, to subpathway, to inflammatory level. Conclusions In conclusion, this study shows that functionally grouping common and rare genetic variants enables the elucidation IL-1-mediated biological mechanisms, specifically, for IL-1β and IL-6 cytokine responses induced by various stimuli. The framework used in this study may allow for the analysis of rare and common genetic variants in a wider variety of (non-immune) complex phenotypes and therefore has the potential to contribute to better understanding of unresolved, complex traits and diseases.

scholarly journals Crossing design shapes patterns of genetic variation in synthetic recombinant populations of Saccharomyces cerevisiae

2021 ◽  
Author(s):  
Mark A Phillips ◽  
Ian C Kutch ◽  
Molly Burke
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Genetic Variation ◽  
Experimental Evolution ◽  
Complex Traits ◽  
De Novo ◽  
Equal Proportion ◽  
Combination Strategies ◽  
The Impact ◽  
Isogenic Strains ◽  
Recombinant Population

Multiparent or synthetic recombinant populations those created by combining distinct isogenic founders to establish a single recombinant background have emerged as a useful tool for dissecting the genetics of complex traits. Synthetic recombinant populations can be used to derive inbred lines in which quantitative traits can be mapped, or the recombinant populations themselves can be sampled for experimental evolution. Especially for the latter application, investigators generally value maximizing genetic variation in a recombinant population; in other words, a population harboring relatively equal contributions of the genetic backgrounds of each isogenic founder strain is a desirable resource. It is well-documented that in evolution experiments initiated from recombinant or outbred ancestral populations, the subsequent adaptation that occurs in evolved populations is driven by standing genetic variation, rather than de novo mutations. Despite the demonstrated importance of initial genetic variation to the adaptive process, little has been done to systematically evaluate methods of constructing a synthetic recombinant population, for creating resources for evolution experiments. Here we seek to address this issue by comparing patterns of genetic variation in different synthetic recombinant populations of Saccharomyces cerevisiae created using one of two combination strategies: pairwise crossing of isogenic strains or simple mixing of strains in equal proportion. We also explore the impact of the varying the number of parental strains used in each strategy. We find that more genetic variation is initially present and subsequently maintained over generations when population construction includes a round of pairwise crossing. We also observe that when using a given crossing strategy, increasing the number of parental strains typically increases genetic diversity. In summary, we suggest that when creating recombinant populations for use in experimental evolution studies, simply mixing founder strains in equal proportion may limit the adaptive potential of that population.

scholarly journals Genetic dissection of MAPK-mediated complex traits acrossS. cerevisiae

2014 ◽  
Author(s):  
Sebastian Treusch ◽  
Frank W Albert ◽  
Joshua S Bloom ◽  
Iulia E Kotenko ◽  
Leonid Kruglyak
Keyword(s):  
Genetic Variation ◽  
Signaling Pathways ◽  
Genetic Variants ◽  
Complex Traits ◽  
Phenotypic Diversity ◽  
Mapk Signaling ◽  
Signaling Cascades ◽  
Genetic Dissection ◽  
Systematic Assessment ◽  
The Impact

Signaling pathways enable cells to sense and respond to their environment. Many cellular signaling strategies are conserved from fungi to humans, yet their activity and phenotypic consequences can vary extensively among individuals within a species. A systematic assessment of the impact of naturally occurring genetic variation on signaling pathways remains to be conducted. InS. cerevisiae, both response and resistance to stressors that activate signaling pathways differ between diverse isolates. Here, we present a quantitative trait locus (QTL) mapping approach that enables us to identify genetic variants underlying such phenotypic differences across the genetic and phenotypic diversity ofS. cerevisiae. Using a Round-robin cross between twelve diverse strains, we determined the genetic architectures of phenotypes critically dependent on MAPK signaling cascades. Genetic variants identified fell within MAPK signaling networks themselves as well as other interconnected signaling pathways, illustrating how genetic variation can shape the phenotypic output of highly conserved signaling cascades.

scholarly journals Long-Term Experimental Evolution in Escherichia coli. VI. Environmental Constraints on Adaptation and Divergence

Genetics ◽  
1997 ◽  
Vol 146 (2) ◽  
pp. 471-479 ◽  
Author(s):  
Michael Travisano
Keyword(s):  
Escherichia Coli ◽  
Genetic Variation ◽  
Experimental Evolution ◽  
Population Genetic ◽  
Environmental Constraints ◽  
Asymmetric Pattern ◽  
Nutrient Environment ◽  
Mean Fitness ◽  
Population Genetic Variation

The effect of environment on adaptation and divergence was examined in two sets of populations of Escherichia coli selected for 1000 generations in either maltose- or glucose-limited media. Twelve replicate populations selected in maltose-limited medium improved in fitness in the selected environment, by an average of 22.5%. Statistically significant among-population genetic variation for fitness was observed during the course of the propagation, but this variation was small relative to the fitness improvement. Mean fitness in a novel nutrient environment, glucose-limited medium, improved to the same extent as in the selected environment, with no statistically significant among-population genetic variation. In contrast, 12 replicate populations previously selected for 1000 generations in glucose-limited medium showed no improvement, as a group, in fitness in maltose-limited medium and substantial genetic variation. This asymmetric pattern of correlated responses suggests that small changes in the environment can have profound effects on adaptation and divergence.

Studying how genetic variants affect mechanism in biological systems

2018 ◽  
Vol 62 (4) ◽  
pp. 575-582
Author(s):  
Francesco Raimondi ◽  
Robert B. Russell
Keyword(s):  
Genetic Variation ◽  
Molecular Mechanism ◽  
Genetic Variants ◽  
Biological Function ◽  
Biological Systems ◽  
Protein Structures ◽  
Clinical Applications ◽  
Biological Pathways ◽  
The Relationship

Genetic variants are currently a major component of system-wide investigations into biological function or disease. Approaches to select variants (often out of thousands of candidates) that are responsible for a particular phenomenon have many clinical applications and can help illuminate differences between individuals. Selecting meaningful variants is greatly aided by integration with information about molecular mechanism, whether known from protein structures or interactions or biological pathways. In this review we discuss the nature of genetic variants, and recent studies highlighting what is currently known about the relationship between genetic variation, biomolecular function, and disease.

scholarly journals Sex, amitosis, and evolvability in the ciliate Tetrahymena thermophila

2021 ◽  
Author(s):  
Jason A Tarkington ◽  
Hao Zhang ◽  
Ricardo Azevedo ◽  
Rebecca Zufall
Keyword(s):  
Genetic Variation ◽  
Experimental Evolution ◽  
Evolutionary Biology ◽  
Genetic Architecture ◽  
Nuclear Division ◽  
Tetrahymena Thermophila ◽  
Laboratory Populations ◽  
Evolutionary Success ◽  
Sexual Progeny ◽  
Open Question

Understanding the mechanisms that generate genetic variation, and thus contribute to the process of adaptation, is a major goal of evolutionary biology. Mutation and genetic exchange have been well studied as mechanisms to generate genetic variation. However, there are additional processes that may also generate substantial genetic variation in some populations and the extent to which these variation generating mechanisms are themselves shaped by natural selection is still an open question. Tetrahymena thermophila is a ciliate with an unusual mechanism of nuclear division, called amitosis, which can generate genetic variation among the asexual descendants of a newly produced sexual progeny. We hypothesize that amitosis thus increases the evolvability of newly produced sexual progeny relative to species that undergo mitosis. To test this hypothesis, we used experimental evolution and simulations to compare the rate of adaptation in T. thermophila populations founded by a single sexual progeny to parental populations that had not had sex in many generations. The populations founded by a sexual progeny adapted more quickly than parental populations in both laboratory populations and simulated populations. This suggests that the additional genetic variation generated by amitosis of a heterozygote can increase the rate of adaptation following sex and may help explain the evolutionary success of the unusual genetic architecture of Tetrahymena and ciliates more generally.

scholarly journals A global analysis of CNVs in Chinese indigenous fine-wool sheep populations using whole-genome resequencing

2021 ◽  
Author(s):  
Chao Yuan ◽  
Zengkui Lu ◽  
Tingting Guo ◽  
Yaojing Yue ◽  
Xijun Wang ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Complex Traits ◽  
Phenotypic Diversity ◽  
Average Length ◽  
Global Analysis ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Nutrient Metabolism ◽  
Relaxin Family

Abstract Background Copy number variation (CNV) is an important source of genetic variation that has a significant influence on phenotypic diversity, economically important traits and the evolution of livestock species. In this study, the genome-wide CNV distribution characteristics of 32 fine-wool sheep from three breeds were analyzed using resequencing.Results A total of 1,747,604 CNVs were detected in this study, and 7,228 CNV regions (CNVR) were obtained after merging overlapping CNVs; these regions accounted for 2.17% of the sheep reference genome. The average length of the CNVRs was 4,307.17 bp. “Deletion” events took place more frequently than “duplication” or “both” events. The CNVRs obtained overlapped with previously reported sheep CNVRs to variable extents (4.39%–55.46%). Functional enrichment analysis showed that the CNVR-harboring genes were mainly involved in sensory perception systems, nutrient metabolism processes, and growth and development processes. Furthermore, 1,855 of the CNVRs were associated with 166 quantitative trait loci (QTL), including milk QTLs, carcass QTLs, and health-related QTLs, among others. In addition, the 32 fine-wool sheep were divided into horned and polled groups to analyze for the selective sweep of CNVRs, and it was found that the relaxin family peptide receptor 2 (RXFP2) gene was strongly influenced by selection.Conclusions In summary, we constructed a genomic CNV map for Chinese indigenous fine-wool sheep using resequencing, thereby providing a valuable genetic variation resource for sheep genome research, which will contribute to the study of complex traits in sheep.

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