scholarly journals Empirical measures of mutational effects define neutral models of regulatory evolution in Saccharomyces cerevisiae

2019 ◽  
Vol 116 (42) ◽  
pp. 21085-21093 ◽  
Author(s):  
Andrea Hodgins-Davis ◽  
Fabien Duveau ◽  
Elizabeth A. Walker ◽  
Patricia J. Wittkopp
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Phenotypic Variation ◽  
Natural Populations ◽  
Point Mutations ◽  
Regulatory Evolution ◽  
Empirical Measures ◽  
Expression Variation ◽  
Neutral Models ◽  
New Mutations

Understanding how phenotypes evolve requires disentangling the effects of mutation generating new variation from the effects of selection filtering it. Tests for selection frequently assume that mutation introduces phenotypic variation symmetrically around the population mean, yet few studies have tested this assumption by deeply sampling the distributions of mutational effects for particular traits. Here, we examine distributions of mutational effects for gene expression in the budding yeast Saccharomyces cerevisiae by measuring the effects of thousands of point mutations introduced randomly throughout the genome. We find that the distributions of mutational effects differ for the 10 genes surveyed and are inconsistent with normality. For example, all 10 distributions of mutational effects included more mutations with large effects than expected for normally distributed phenotypes. In addition, some genes also showed asymmetries in their distribution of mutational effects, with new mutations more likely to increase than decrease the gene’s expression or vice versa. Neutral models of regulatory evolution that take these empirically determined distributions into account suggest that neutral processes may explain more expression variation within natural populations than currently appreciated.

scholarly journals Empirical measures of mutational effects define neutral models of regulatory evolution in Saccharomyces cerevisiae

2019 ◽  
Author(s):  
Andrea Hodgins-Davis ◽  
Fabien Duveau ◽  
Elizabeth Walker ◽  
Patricia J Wittkopp
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Natural Populations ◽  
Point Mutations ◽  
Evolutionary Models ◽  
Phenotypic Evolution ◽  
Regulatory Evolution ◽  
Empirical Measures ◽  
Neutral Models ◽  
New Mutations ◽  
Neutral Expression

AbstractUnderstanding how phenotypes evolve requires disentangling the effects of mutation generating new variation from the effects of selection filtering it. Evolutionary models frequently assume that mutation introduces phenotypic variation symmetrically around the population mean, yet few studies have tested this assumption by deeply sampling the distributions of mutational effects for particular traits. Here, we examine distributions of mutational effects for gene expression in the budding yeast Saccharomyces cerevisiae by measuring the effects of thousands of point mutations introduced randomly throughout the genome. We find that the distributions of mutational effects differ for the 10 genes surveyed and violate the assumption of normality. For example, all ten distributions of mutational effects included more mutations with large effects than expected for normally distributed phenotypes. In addition, some genes also showed asymmetries in their distribution of mutational effects, with new mutations more likely to increase than decrease the gene’s expression or vice versa. Neutral models of regulatory evolution that take these empirically determined distributions into account suggest that neutral processes may explain more expression variation within natural populations than currently appreciated.Significance statementNew mutations tend to arise randomly throughout the genome, but their phenotypic effects are often not random. This disconnect results from interactions among genes that define the genotype-phenotype map. The structure of this map is poorly known and different for each trait, making it challenging to predict the distribution of mutational effects for specific phenotypes. Empirical measures of the distribution of mutational effects are thus necessary to understand how traits can change in the absence of natural selection. In this work, we define such distributions for expression of ten genes in S. cerevisiae and show that they predict greater neutral expression divergence than commonly used models of phenotypic evolution.

Gene expression variation in natural populations of hexaploid and allododecaploid Spartina species (Poaceae)

2017 ◽  
Vol 303 (8) ◽  
pp. 1061-1079 ◽  
Author(s):  
Julie Ferreira de Carvalho ◽  
Julien Boutte ◽  
Pierre Bourdaud ◽  
Houda Chelaifa ◽  
Kader Ainouche ◽  
...  
Keyword(s):  
Gene Expression ◽  
Natural Populations ◽  
Gene Expression Variation ◽  
Expression Variation ◽  
Spartina Species

scholarly journals Population-scale long-read sequencing uncovers transposable elements contributing to gene expression variation and associated with adaptive signatures in Drosophila melanogaster

2021 ◽  
Author(s):  
Gabriel Rech ◽  
Santiago Radio ◽  
Sara Guirao-Rico ◽  
Laura Aguilera ◽  
Vivien Horvath ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genetic Variation ◽  
Transposable Elements ◽  
Natural Populations ◽  
Gene Expression Variation ◽  
High Quality ◽  
Expression Variation ◽  
Climatic Regions ◽  
Genomic Studies ◽  
Reference Genomes

High quality reference genomes are crucial to understanding genome function, structure and evolution. The availability of reference genomes has allowed us to start inferring the role of genetic variation in biology, disease, and biodiversity conservation. However, analyses across organisms demonstrate that a single reference genome is not enough to capture the global genetic diversity present in populations. In this work, we generated 32 high-quality reference genomes for the well-known model species D. melanogaster and focused on the identification and analysis of transposable element variation as they are the most common type of structural variant. We showed that integrating the genetic variation across natural populations from five climatic regions increases the number of detected insertions by 58%. Moreover, 26% to 57% of the insertions identified using long-reads were missed by short-reads methods. We also identified hundreds of transposable elements associated with gene expression variation and new TE variants likely to contribute to adaptive evolution in this species. Our results highlight the importance of incorporating the genetic variation present in natural populations to genomic studies, which is essential if we are to understand how genomes function and evolve.

scholarly journals The roles of plasticity and evolutionary change in shaping gene expression variation in natural populations of extremophile fish

2017 ◽  
Vol 26 (22) ◽  
pp. 6384-6399 ◽  
Author(s):  
Courtney N. Passow ◽  
Chathurika Henpita ◽  
Jennifer H. Shaw ◽  
Corey R. Quackenbush ◽  
Wesley C. Warren ◽  
...  
Keyword(s):  
Gene Expression ◽  
Natural Populations ◽  
Evolutionary Change ◽  
Gene Expression Variation ◽  
Expression Variation

scholarly journals Spatial variation in gene expression of Tasmanian devil facial tumors despite minimal host transcriptomic response to infection

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Christopher P. Kozakiewicz ◽  
Alexandra K. Fraik ◽  
Austin H. Patton ◽  
Manuel Ruiz-Aravena ◽  
David G. Hamilton ◽  
...  
Keyword(s):  
Gene Expression ◽  
Phenotypic Variation ◽  
Population Level ◽  
Host Responses ◽  
Tasmanian Devil ◽  
Population Declines ◽  
Transcriptomic Response ◽  
Expression Variation ◽  
Normal Tissues ◽  
Cancer Phenotypes

Abstract Background Transmissible cancers lie at the intersection of oncology and infectious disease, two traditionally divergent fields for which gene expression studies are particularly useful for identifying the molecular basis of phenotypic variation. In oncology, transcriptomics studies, which characterize the expression of thousands of genes, have identified processes leading to heterogeneity in cancer phenotypes and individual prognoses. More generally, transcriptomics studies of infectious diseases characterize interactions between host, pathogen, and environment to better predict population-level outcomes. Tasmanian devils have been impacted dramatically by a transmissible cancer (devil facial tumor disease; DFTD) that has led to widespread population declines. Despite initial predictions of extinction, populations have persisted at low levels, due in part to heterogeneity in host responses, particularly between sexes. However, the processes underlying this variation remain unknown. Results We sequenced transcriptomes from healthy and DFTD-infected devils, as well as DFTD tumors, to characterize host responses to DFTD infection, identify differing host-tumor molecular interactions between sexes, and investigate the extent to which tumor gene expression varies among host populations. We found minimal variation in gene expression of devil lip tissues, either with respect to DFTD infection status or sex. However, 4088 genes were differentially expressed in tumors among our sampling localities. Pathways that were up- or downregulated in DFTD tumors relative to normal tissues exhibited the same patterns of expression with greater intensity in tumors from localities that experienced DFTD for longer. No mRNA sequence variants were associated with expression variation. Conclusions Expression variation among localities may reflect morphological differences in tumors that alter ratios of normal-to-tumor cells within biopsies. Phenotypic variation in tumors may arise from environmental variation or differences in host immune response that were undetectable in lip biopsies, potentially reflecting variation in host-tumor coevolutionary relationships among sites that differ in the time since DFTD arrival.

scholarly journals Cis-regulatory evolution spotlights species differences in the adaptive potential of gene expression plasticity

2020 ◽  
Author(s):  
F. He ◽  
K. A. Steige ◽  
V. Kovacova ◽  
U. Göbel ◽  
M. Bouzid ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plastic Response ◽  
Regulatory Evolution ◽  
Individual Fitness ◽  
Regulatory Variants ◽  
Regulatory Changes ◽  
Direction Of Effects ◽  
Selective Forces ◽  
Response To Stress ◽  
New Mutations

AbstractPhenotypic plasticity is the variation in phenotype that a single genotype can produce in different environments and, as such, is an important component of individual fitness. However, whether the effect of new mutations, and hence evolution, depends on the direction of plasticity remains controversial. Here, we identify the cis-acting modifications that have reshaped gene expression in response to dehydration stress in three Arabidopsis species. Our study shows that the direction of effects of most cis-regulatory variants differentiating the response between A. thaliana and the sister species A. lyrata and A. halleri depends on the direction of pre-existing plasticity in gene expression. A comparison of the rate of cis-acting variant accumulation in each lineage indicates that the selective forces driving adaptive evolution in gene expression favors regulatory changes that magnify the stress response in A. lyrata. The evolutionary constraints measured on the amino-acid sequence of these genes support this interpretation. In contrast, regulatory changes that mitigate the plastic response to stress evolved more frequently in A. halleri. Our results demonstrate that pre-existing plasticity can be a stepping stone for adaptation, but its selective remodeling differs between lineages.

scholarly journals Cis-regulatory evolution spotlights species differences in the adaptive potential of gene expression plasticity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
F. He ◽  
K. A. Steige ◽  
V. Kovacova ◽  
U. Göbel ◽  
M. Bouzid ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulatory Evolution ◽  
Cis Acting ◽  
Individual Fitness ◽  
Regulatory Variants ◽  
Regulatory Changes ◽  
Direction Of Effects ◽  
Selective Forces ◽  
Response To Stress ◽  
New Mutations

AbstractPhenotypic plasticity is the variation in phenotype that a single genotype can produce in different environments and, as such, is an important component of individual fitness. However, whether the effect of new mutations, and hence evolution, depends on the direction of plasticity remains controversial. Here, we identify the cis-acting modifications that have reshaped gene expression in response to dehydration stress in three Arabidopsis species. Our study shows that the direction of effects of most cis-regulatory variants differentiating the response between A. thaliana and the sister species A. lyrata and A. halleri depends on the direction of pre-existing plasticity in gene expression. A comparison of the rate of cis-acting variant accumulation in each lineage indicates that the selective forces driving adaptive evolution in gene expression favors regulatory changes that magnify the stress response in A. lyrata. The evolutionary constraints measured on the amino-acid sequence of these genes support this interpretation. In contrast, regulatory changes that mitigate the plastic response to stress evolved more frequently in A. halleri. Our results demonstrate that pre-existing plasticity may be a stepping stone for adaptation, but its selective remodeling differs between lineages.

scholarly journals Uses and Advantages of CRISPR/Cas Genetic Edition in Yeasts

2018 ◽  
Author(s):  
Daniela Amado ◽  
Norida Velez ◽  
Andres Ceballos-Garzon ◽  
Juan Monroy ◽  
Claudia-Marcela Parra-Giraldo
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Pichia Pastoris ◽  
Point Mutations ◽  
Control Group ◽  
Candida Sp ◽  
Advantages And Disadvantages ◽  
Crispr System ◽  
Saccharomyces Pastorianus ◽  
System Information

This review summarizes the use of CRISPR system in yeasts, identifying advantages and disadvantages of its applications. 39 articles were evaluated including 12 articles that discussed the advantages of new CRISPR systems that improved the initial system, and another 27 were evaluated, among these: three were applications in Cryptococcus neoformans, four in candida sp., three in Schizosaccharomyces pombe, nine in Saccharomyces cerevisiae, four in Yarrowia lipolytica, and four in industrially important yeasts such as Pichia pastoris and Saccharomyces pastorianus. It was concluded that the CRISPR system is one of the most versatile genetic editing systems available nowadays. It can be applied in different organisms for several effects including gene knock-outs, performing point mutations, gene expression, or even applying multiple edition operations in several genes. However, we recognize that numerous studies lack a control group of the mutated strains, which leaves many questions unanswered. For instance, the extent and precision of this techniques, it also represents a risk to biosecurity standards. Therefore, this review shows the compilation of CRISPR system information, which could be used to generate different alternatives in the industry and clinical fields.

scholarly journals Complex polymorphic genetic architecture underlies trans-regulatory variation among strains of Saccharomyces cerevisiae

2019 ◽  
Author(s):  
Brian P. H. Metzger ◽  
Patricia J. Wittkopp
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Genetic Architecture ◽  
Promoter Activity ◽  
Reference Strain ◽  
Stabilizing Selection ◽  
Empirical Measures ◽  
Regulatory Variation ◽  
Multiple Strains ◽  
Opposing Effects

AbstractHeritable variation in gene expression is common within species. Much of this variation is due to genetic changes at loci other than the affected gene and is thus trans-acting. This trans-regulatory variation is often polygenic, with individual variants typically having small effects, making the genetic architecture of trans-regulatory variation challenging to study. Consequently, key questions about trans-regulatory variation remain, including how selection affects this variation and how trans-regulatory variants are distributed throughout the genome and within species. Here, we show that trans-regulatory variation affecting TDH3 promoter activity is common among strains of Saccharomyces cerevisiae. Comparing this variation to neutral models of trans-regulatory evolution based on empirical measures of mutational effects revealed that stabilizing selection has constrained this variation. Using a powerful quantitative trait locus (QTL) mapping method, we identified ∼100 loci altering expression between a reference strain and each of three genetically distinct strains. In all three cases, the non-reference strain alleles increased and decreased TDH3 promoter activity with similar frequencies, suggesting that stabilizing selection maintained many trans-acting variants with opposing effects. Loci altering expression were located throughout the genome, with many loci being strain specific and others being shared among multiple strains. These findings are consistent with theory showing stabilizing selection for quantitative traits can maintain many alleles with opposing effects, and the wide-spread distribution of QTL throughout the genome is consistent with the omnigenic model of complex trait variation. Furthermore, the prevalence of alleles with opposing effects might provide raw material for compensatory evolution and developmental systems drift.Significance statementGene expression varies among individuals in a population due to genetic differences in regulatory components. To determine how this variation is distributed within genomes and species, we used a powerful genetic mapping approach to examine multiple strains of Saccharomyces cerevisiae. Despite evidence of stabilizing selection maintaining gene expression levels among strains, we find hundreds of loci that affect expression of a single gene. These loci vary among strains and include similar frequencies of alleles that increase and decrease expression. As a result, each strain contains a unique set of compensatory alleles that lead to similar levels of gene expression among strains. This regulatory variation might form the basis for large scale regulatory rewiring observed between distantly related species.

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