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 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 Environmental perturbations lead to extensive directional shifts in RNA processing

2017 ◽  
Author(s):  
A. L. Richards ◽  
D. Watza ◽  
A. Findley ◽  
A. Alazizi ◽  
X. Wen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genetic Variation ◽  
Rna Processing ◽  
Complex Traits ◽  
Intron Retention ◽  
Vast Number ◽  
Factor Binding ◽  
Environmental Perturbations ◽  
Exon Usage ◽  
The Impact

AbstractEnvironmental perturbations have large effects on both organismal and cellular traits, including gene expression, but the extent to which the environment affects RNA processing remains largely uncharacterized. Recent studies have identified a large number of genetic variants associated with variation in RNA processing that also have an important role in complex traits; yet we do not know in which contexts the different underlying isoforms are used. Here, we comprehensively characterized changes in RNA processing events across 89 environments in five human cell types and identified 15,300 event shifts (FDR = 15%) comprised of eight event types in over 4,000 genes. Many of these changes occur consistently in the same direction across conditions, indicative of global regulation by trans factors. Accordingly, we demonstrate that environmental modulation of splicing factor binding predicts shifts in intron retention, and that binding of transcription factors predicts shifts in AFE usage in response to specific treatments. We validated the mechanism hypothesized for AFE in two independent datasets. Using ATAC-seq, we found altered binding of 64 factors in response to selenium at sites of AFE shift, including ELF2 and other factors in the ETS family. We also performed AFE QTL mapping in 373 individuals and found an enrichment for SNPs predicted to disrupt binding of the ELF2 factor. Together, these results demonstrate that RNA processing is dramatically changed in response to environmental perturbations through specific mechanisms regulated by trans factors.Author SummaryChanges in a cell’s environment and genetic variation have been shown to impact gene expression. Here, we demonstrate that environmental perturbations also lead to extensive changes in alternative RNA processing across a large number of cellular environments that we investigated. These changes often occur in a non-random manner. For example, many treatments lead to increased intron retention and usage of the downstream first exon. We also show that the changes to first exon usage are likely dependent on changes in transcription factor binding. We provide support for this hypothesis by considering how first exon usage is affected by disruption of binding due to treatment with selenium. We further validate the role of a specific factor by considering the effect of genetic variation in its binding sites on first exon usage. These results help to shed light on the vast number of changes that occur in response to environmental stimuli and will likely aid in understanding the impact of compounds to which we are daily exposed.

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 Deficiency of Polη in Saccharomyces cerevisiae reveals the impact of transcription on damage-induced cohesion

PLoS Genetics ◽  
2021 ◽  
Vol 17 (9) ◽  
pp. e1009763
Author(s):  
Pei-Shang Wu ◽  
Jan Grosser ◽  
Donald P. Cameron ◽  
Laura Baranello ◽  
Lena Ström
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Rna Polymerase Ii ◽  
De Novo ◽  
Regulation Of Transcription ◽  
Null Mutant ◽  
Coding Regions ◽  
Chromatid Cohesion ◽  
Structural Maintenance Of Chromosome ◽  
Histone Exchange ◽  
The Impact

The structural maintenance of chromosome (SMC) complex cohesin mediates sister chromatid cohesion established during replication, and damage-induced cohesion formed in response to DSBs post-replication. The translesion synthesis polymerase Polη is required for damage-induced cohesion through a hitherto unknown mechanism. Since Polη is functionally associated with transcription, and transcription triggers de novo cohesion in Schizosaccharomyces pombe, we hypothesized that transcription facilitates damage-induced cohesion in Saccharomyces cerevisiae. Here, we show dysregulated transcriptional profiles in the Polη null mutant (rad30Δ), where genes involved in chromatin assembly and positive transcription regulation were downregulated. In addition, chromatin association of RNA polymerase II was reduced at promoters and coding regions in rad30Δ compared to WT cells, while occupancy of the H2A.Z variant (Htz1) at promoters was increased in rad30Δ cells. Perturbing histone exchange at promoters inactivated damage-induced cohesion, similarly to deletion of the RAD30 gene. Conversely, altering regulation of transcription elongation suppressed the deficient damage-induced cohesion in rad30Δ cells. Furthermore, transcription inhibition negatively affected formation of damage-induced cohesion. These results indicate that the transcriptional deregulation of the Polη null mutant is connected with its reduced capacity to establish damage-induced cohesion. This also suggests a linkage between regulation of transcription and formation of damage-induced cohesion after replication.

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.

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