Pengyao Jiang | University of Chicago (original) (raw)

Papers by Pengyao Jiang

Genetics, Feb 1, 2014

The identification and validation of gene-gene interactions is a major challenge in human studies... more The identification and validation of gene-gene interactions is a major challenge in human studies. Here, we explore an approach for studying epistasis in humans using a Drosophila melanogaster model of neonatal diabetes mellitus. Expression of the mutant preproinsulin (hINS C96Y) in the eye imaginal disc mimics the human disease: it activates conserved stress-response pathways and leads to cell death (reduction in eye area). Dominant-acting variants in wild-derived inbred lines from the Drosophila Genetics Reference Panel produce a continuous, highly heritable distribution of eye-degeneration phenotypes in a hINS C96Y background. A genome-wide association study (GWAS) in 154 sequenced lines identified a sharp peak on chromosome 3L, which mapped to a 400-bp linkage block within an intron of the gene sulfateless (sfl). RNAi knockdown of sfl enhanced the eye-degeneration phenotype in a mutant-hINS-dependent manner. RNAi against two additional genes in the heparan sulfate (HS) biosynthetic pathway (ttv and botv), in which sfl acts, also modified the eye phenotype in a hINS C96Y-dependent manner, strongly suggesting a novel link between HS-modified proteins and cellular responses to misfolded proteins. Finally, we evaluated allele-specific expression difference between the two major sfl-intronic haplotypes in heterozygtes. The results showed significant heterogeneity in marker-associated gene expression, thereby leaving the causal mutation(s) and its mechanism unidentified. In conclusion, the ability to create a model of human genetic disease, map a QTL by GWAS to a specific gene, and validate its contribution to disease with available genetic resources and the potential to experimentally link the variant to a molecular mechanism demonstrate the many advantages Drosophila holds in determining the genetic underpinnings of human disease.

Current Opinion in Genetics & Development, Oct 1, 2022

arXiv (Cornell University), Aug 6, 2011

Under the effects of strong genetic drift, it is highly probable to observe gene fixation or loss... more Under the effects of strong genetic drift, it is highly probable to observe gene fixation or loss in a population, shown by divergent probability density functions, or infinite adaptive peaks on a landscape. It is then interesting to ask what such infinite peaks imply, with or without combining other biological factors (e.g. mutation and selection). We study the stochastic escape time from the generated infinite adaptive peaks, and show that Kramers' classical escape formula can be extended to the non-Gaussian distribution cases. The constructed landscape provides a global description for system's middle and long term behaviors, breaking the constraints in previous methods.

Iet Systems Biology, Oct 1, 2013

Adaptive landscape, proposed by Sewall Wright, has provided a conceptual framework to describe dy... more Adaptive landscape, proposed by Sewall Wright, has provided a conceptual framework to describe dynamical behaviours. However, it is still a challenge to explicitly construct such a landscape, and apply it to quantify interesting evolutionary processes. This is particularly true for neutral evolution. In this work, the authors study one‐dimensional Wright Fisher process, and analytically obtain an adaptive landscape as a potential function. They provide the complete characterisation for dynamical behaviours of all possible mutation rates under the influence of mutation and random drift. This same analysis has been applied to situations with additive selection and random drift for all possible selection rates. The critical state dividing the basins of two stable states is directly obtained by the landscape. In addition, the landscape is able to handle situations with pure random drift, which would be non‐normalisable for its stationary distribution. The nature of non‐normalisation is from the singularity of adaptive landscape. In addition, they propose a new type of neutral evolution. It has the same probability for all possible states. The new type of neutral evolution describes the non‐neutral alleles with 0%. They take the equal effect of mutation and random drift as an example.

Physical Review E, Jan 31, 2014

Under the effect of strong genetic drift, it is highly probable to observe gene fixation or gene ... more Under the effect of strong genetic drift, it is highly probable to observe gene fixation or gene loss in a population, shown by infinite peaks on a coherently constructed potential energy landscape. It is then important to ask what such singular peaks imply, with or without the effects of other biological factors. We studied the stochastic escape time from the infinite potential peaks in the Wright-Fisher model, where the typical two-scale diffusion dynamics was observed via computer simulations. We numerically found the average escape time for all the bi-stable cases and analytically approximated the results under weak mutations and selections by calculating the mean first passage time (MFPT) in singular potential peak. Our results showed that Kramers' classical escape formula can be extended to the models with non-Gaussian probability distributions, overcoming constraints in previous methods. The constructed landscape provides a global and coherent description for system's evolutionary dynamics, allowing new biological results to be generated.

Developmental Biology, Sep 1, 2015

The evolution of canalized traits is a central question in evolutionary biology. Natural variatio... more The evolution of canalized traits is a central question in evolutionary biology. Natural variation in highly conserved traits can provide clues about their evolutionary potential. Here we investigate natural variation in a conserved trait-even-skipped (eve) expression at the cellular blastoderm stage of embryonic development in Drosophila melanogaster. Expression of the pair-rule gene eve was quantitatively measured in three inbred lines derived from a natural population of D. melanogaster. One line showed marked differences in the spacing, amplitude and timing of formation of the characteristic seven-striped pattern over a fifty-minute period prior to the onset of gastrulation. Stripe 5 amplitude and the width of the interstripe between stripes 4 and 5 were both reduced in this line, while the interstripe distance between stripes 3 and 4 was increased. Engrailed expression in stage 10 embryos revealed a statistically significant increase in the length of parasegment 6 and a decrease in the length of parasegments 8 and 9. These changes are larger than those previously reported between D. melanogaster and D. pseudoobscura, two species that are thought to have diverged from a common ancestor over 25 million years ago. This line harbors a rare 448bp deletion in the first intron of knirps (kni). This finding suggested that reduced Kni levels caused the deviant eve expression, and indeed we observed lower levels of Kni protein at early cycle 14A in L2 compared to the other two lines. A second of the three lines displayed an approximately 20% greater level of expression for all seven eve stripes. The three lines are each viable and fertile, and none display a segmentation defect as adults, suggesting that early-acting variation in eve expression is ameliorated by developmental buffering mechanisms acting later in development. Canalization of the segmentation pathway may reduce the fitness consequences of genetic variation, thus allowing the persistence of mutations with unexpectedly strong gene expression phenotypes.

eLife, Sep 15, 2021

Although studies of Saccharomyces cerevisiae have provided many insights into mutagenesis and DNA... more Although studies of Saccharomyces cerevisiae have provided many insights into mutagenesis and DNA repair, most of this work has focused on a few laboratory strains. Much less is known about the phenotypic effects of natural variation within S. cerevisiae's DNA repair pathways. Here, we use natural polymorphisms to detect historical mutation spectrum differences among several wild and domesticated S. cerevisiae strains. To determine whether these differences are likely caused by genetic mutation rate modifiers, we use a modified fluctuation assay with a CAN1 reporter to measure de novo mutation rates and spectra in 16 of the analyzed strains. We measure a 10-fold range of mutation rates and identify two strains with distinctive mutation spectra. These strains, known as AEQ and AAR, come from the panel's 'Mosaic beer' clade and share an enrichment for C > A mutations that is also observed in rare variation segregating throughout the genomes of several Mosaic beer and Mixed origin strains. Both AEQ and AAR are haploid derivatives of the diploid natural isolate CBS 1782, whose rare polymorphisms are enriched for C > A as well, suggesting that the underlying mutator allele is likely active in nature. We use a plasmid complementation test to show that AAR and AEQ share a mutator allele in the DNA repair gene OGG1, which excises 8-oxoguanine lesions that can cause C > A mutations if left unrepaired.

We study the transition time between different metastable states in the continuous Wright-Fisher ... more We study the transition time between different metastable states in the continuous Wright-Fisher (diffusion) model. We construct an adaptive landscape for describing the system both qualitatively and quantitatively. When strong genetic drift and weak mutation generate infinite adaptive peaks, we calculate the expected time to escape from such peak states. We find a new way to analytically approximate the escape time, which extends the application of Kramer's classical formulae to the cases of non-Gaussian equilibrium distribution and bridges previous results in two limits. Our adaptive landscape, compared to the classical fitness landscape or other scalar functions, is directly related to system's middle-and-long-term dynamics and is self-consistent in the whole parameter space. Our work provides a complete description for the bi-stabilities in the present model.

bioRxiv (Cold Spring Harbor Laboratory), Sep 27, 2021

Developmental robustness (canalization) is a common attribute of traits in multi-cellular organis... more Developmental robustness (canalization) is a common attribute of traits in multi-cellular organisms. High robustness ensures the reproducibility of phenotypes in the face of environmental and developmental noise, but it also dampens the expression of genetic mutation, the fuel for adaptive evolution. A reduction in robustness may therefore be adaptive under certain evolutionary scenarios. To better understand how robustness influences phenotypic evolution, and to decipher conditions under which canalization itself evolves, a genetic model was constructed in which phenotype is explicitly represented as a collection of traits, calculated from genotype, and the degree of robustness can be explicitly controlled. The genes were subjected to mutation, altering phenotype and fitness. We then simulated the dynamics of a population evolving under two classes of initial conditions, one in which the population is at a fitness optimum and one in which it is far away. The model is formulated with two robustness parameters in the genotype to phenotype map, controlling robustness over a tight (γ) or a broad (α) range of values. Within the robustness range determined by γ, high robustness results in a equilibrium population fitness closer to the optimal fitness value than low robustness. High robustness should be favored, therefore, under a constant optimal environment. This situation reverses when populations are challenged to evolve to a new phenotype optimum. In this situation, low robustness populations adapt faster than high robustness populations and reach higher equilibrium mean fitness. A larger set of phenotypes are accessable by mutation when robustness is low, in part explaining why low robustness is favored under this condition. A larger range of robustness could be sampled by varying α, revealing a complex relationship between robustness and both the initial rate of phenotypic adaptation as well as the final equilibrium population mean fitness. Intermediate values of α produced a bifurcation in evolutionary trajectories, with some populations remaining at low population mean fitness, and others escaping to achieve high population mean fitness. We then allowed robustness itself to be encoded by a mutable genetic locus that could co-evolve along with the phenotype under selection. Low robustness genotypes are initially favored 2. CC-BY-NC-ND 4.

Studying the genetic and molecular characteristics of brewing yeast strains is crucial for unders... more Studying the genetic and molecular characteristics of brewing yeast strains is crucial for understanding their domestication history and adaptations accumulated over time in fermentation environments, and for guiding optimizations to the brewing process itself. Saccharomyces cerevisiae (brewing yeast) is amongst the most profiled organisms on the planet, yet the temporal molecular changes that underlie industrial fermentation and beer brewing remain understudied. Here, we characterized the genomic makeup of a Saccharomyces cerevisiae ale yeast widely used in the production of Hefeweizen beers, and applied shotgun mass spectrometry to systematically measure the proteomic changes throughout two fermentation cycles which were separated by 14 rounds of serial repitching. The resulting brewing yeast proteomics resource includes 64,740 protein abundance measurements. We found that this strain possesses typical genetic characteristics of Saccharomyces cerevisiae ale strains and displayed p...

Developmental robustness (canalization) is a common attribute of traits in multi-cellular organis... more Developmental robustness (canalization) is a common attribute of traits in multi-cellular organisms. High robustness ensures the reproducibility of phenotypes in the face of environmental and developmental noise, but it also dampens the expression of genetic mutation, the fuel for adaptive evolution. A reduction in robustness may therefore be adaptive under certain evolutionary scenarios. To better understand how robustness influences phenotypic evolution, and to decipher conditions under which canalization itself evolves, a genetic model was constructed in which phenotype is explicitly represented as a collection of traits, calculated from genotype, and the degree of robustness can be explicitly controlled. The genes were subjected to mutation, altering phenotype and fitness. We then simulated the dynamics of a population evolving under two classes of initial conditions, one in which the population is at a fitness optimum and one in which it is far away. The model is formulated with two robustness parameters in the genotype to phenotype map, controlling robustness over a tight (γ) or a broad (α) range of values. Within the robustness range determined by γ, high robustness results in a equilibrium population fitness closer to the optimal fitness value than low robustness. High robustness should be favored, therefore, under a constant optimal environment. This situation reverses when populations are challenged to evolve to a new phenotype optimum. In this situation, low robustness populations adapt faster than high robustness populations and reach higher equilibrium mean fitness. A larger set of phenotypes are accessable by mutation when robustness is low, in part explaining why low robustness is favored under this condition. A larger range of robustness could be sampled by varying α, revealing a complex relationship between robustness and both the initial rate of phenotypic adaptation as well as the final equilibrium population mean fitness. Intermediate values of α produced a bifurcation in evolutionary trajectories, with some populations remaining at low population mean fitness, and others escaping to achieve high population mean fitness. We then allowed robustness itself to be encoded by a mutable genetic locus that could co-evolve along with the phenotype under selection. Low robustness genotypes are initially favored 2. CC-BY-NC-ND 4.

Journal of Evolutionary Biology

Canalization involves mutational robustness, the lack of phenotypic change as a result of genetic... more Canalization involves mutational robustness, the lack of phenotypic change as a result of genetic mutations. Given the large divergence in phenotype across species, understanding the relationship between high robustness and evolvability has been of interest to both theorists and experimentalists. Although canalization was originally proposed in the context of multicellular organisms, the effect of multicellularity and other classes of hierarchical organization on evolvability has not been considered by theoreticians. We address this issue using a Boolean population model with explicit representation of an environment in which individuals with explicit genotype and a hierarchical phenotype representing multicellularity evolve. Robustness is described by a single real number between zero and one which emerges from the genotype–phenotype map. We find that high robustness is favoured in constant environments, and lower robustness is favoured after environmental change. Multicellularity ...

Current Opinion in Genetics & Development

bioRxiv, Sep 27, 2021

Developmental robustness (canalization) is a common attribute of traits in multi-cellular organis... more Developmental robustness (canalization) is a common attribute of traits in multi-cellular organisms. High robustness ensures the reproducibility of phenotypes in the face of environmental and developmental noise, but it also dampens the expression of genetic mutation, the fuel for adaptive evolution. A reduction in robustness may therefore be adaptive under certain evolutionary scenarios. To better understand how robustness influences phenotypic evolution, and to decipher conditions under which canalization itself evolves, a genetic model was constructed in which phenotype is explicitly represented as a collection of traits, calculated from genotype, and the degree of robustness can be explicitly controlled. The genes were subjected to mutation, altering phenotype and fitness. We then simulated the dynamics of a population evolving under two classes of initial conditions, one in which the population is at a fitness optimum and one in which it is far away. The model is formulated with two robustness parameters in the genotype to phenotype map, controlling robustness over a tight (γ) or a broad (α) range of values. Within the robustness range determined by γ, high robustness results in a equilibrium population fitness closer to the optimal fitness value than low robustness. High robustness should be favored, therefore, under a constant optimal environment. This situation reverses when populations are challenged to evolve to a new phenotype optimum. In this situation, low robustness populations adapt faster than high robustness populations and reach higher equilibrium mean fitness. A larger set of phenotypes are accessable by mutation when robustness is low, in part explaining why low robustness is favored under this condition. A larger range of robustness could be sampled by varying α, revealing a complex relationship between robustness and both the initial rate of phenotypic adaptation as well as the final equilibrium population mean fitness. Intermediate values of α produced a bifurcation in evolutionary trajectories, with some populations remaining at low population mean fitness, and others escaping to achieve high population mean fitness. We then allowed robustness itself to be encoded by a mutable genetic locus that could co-evolve along with the phenotype under selection. Low robustness genotypes are initially favored 2. CC-BY-NC-ND 4.

Genetics, Feb 1, 2014

The identification and validation of gene-gene interactions is a major challenge in human studies... more The identification and validation of gene-gene interactions is a major challenge in human studies. Here, we explore an approach for studying epistasis in humans using a Drosophila melanogaster model of neonatal diabetes mellitus. Expression of the mutant preproinsulin (hINS C96Y) in the eye imaginal disc mimics the human disease: it activates conserved stress-response pathways and leads to cell death (reduction in eye area). Dominant-acting variants in wild-derived inbred lines from the Drosophila Genetics Reference Panel produce a continuous, highly heritable distribution of eye-degeneration phenotypes in a hINS C96Y background. A genome-wide association study (GWAS) in 154 sequenced lines identified a sharp peak on chromosome 3L, which mapped to a 400-bp linkage block within an intron of the gene sulfateless (sfl). RNAi knockdown of sfl enhanced the eye-degeneration phenotype in a mutant-hINS-dependent manner. RNAi against two additional genes in the heparan sulfate (HS) biosynthetic pathway (ttv and botv), in which sfl acts, also modified the eye phenotype in a hINS C96Y-dependent manner, strongly suggesting a novel link between HS-modified proteins and cellular responses to misfolded proteins. Finally, we evaluated allele-specific expression difference between the two major sfl-intronic haplotypes in heterozygtes. The results showed significant heterogeneity in marker-associated gene expression, thereby leaving the causal mutation(s) and its mechanism unidentified. In conclusion, the ability to create a model of human genetic disease, map a QTL by GWAS to a specific gene, and validate its contribution to disease with available genetic resources and the potential to experimentally link the variant to a molecular mechanism demonstrate the many advantages Drosophila holds in determining the genetic underpinnings of human disease.

Current Opinion in Genetics & Development, Oct 1, 2022

arXiv (Cornell University), Aug 6, 2011

Under the effects of strong genetic drift, it is highly probable to observe gene fixation or loss... more Under the effects of strong genetic drift, it is highly probable to observe gene fixation or loss in a population, shown by divergent probability density functions, or infinite adaptive peaks on a landscape. It is then interesting to ask what such infinite peaks imply, with or without combining other biological factors (e.g. mutation and selection). We study the stochastic escape time from the generated infinite adaptive peaks, and show that Kramers' classical escape formula can be extended to the non-Gaussian distribution cases. The constructed landscape provides a global description for system's middle and long term behaviors, breaking the constraints in previous methods.

Iet Systems Biology, Oct 1, 2013

Adaptive landscape, proposed by Sewall Wright, has provided a conceptual framework to describe dy... more Adaptive landscape, proposed by Sewall Wright, has provided a conceptual framework to describe dynamical behaviours. However, it is still a challenge to explicitly construct such a landscape, and apply it to quantify interesting evolutionary processes. This is particularly true for neutral evolution. In this work, the authors study one‐dimensional Wright Fisher process, and analytically obtain an adaptive landscape as a potential function. They provide the complete characterisation for dynamical behaviours of all possible mutation rates under the influence of mutation and random drift. This same analysis has been applied to situations with additive selection and random drift for all possible selection rates. The critical state dividing the basins of two stable states is directly obtained by the landscape. In addition, the landscape is able to handle situations with pure random drift, which would be non‐normalisable for its stationary distribution. The nature of non‐normalisation is from the singularity of adaptive landscape. In addition, they propose a new type of neutral evolution. It has the same probability for all possible states. The new type of neutral evolution describes the non‐neutral alleles with 0%. They take the equal effect of mutation and random drift as an example.

Physical Review E, Jan 31, 2014

Under the effect of strong genetic drift, it is highly probable to observe gene fixation or gene ... more Under the effect of strong genetic drift, it is highly probable to observe gene fixation or gene loss in a population, shown by infinite peaks on a coherently constructed potential energy landscape. It is then important to ask what such singular peaks imply, with or without the effects of other biological factors. We studied the stochastic escape time from the infinite potential peaks in the Wright-Fisher model, where the typical two-scale diffusion dynamics was observed via computer simulations. We numerically found the average escape time for all the bi-stable cases and analytically approximated the results under weak mutations and selections by calculating the mean first passage time (MFPT) in singular potential peak. Our results showed that Kramers' classical escape formula can be extended to the models with non-Gaussian probability distributions, overcoming constraints in previous methods. The constructed landscape provides a global and coherent description for system's evolutionary dynamics, allowing new biological results to be generated.

Developmental Biology, Sep 1, 2015

The evolution of canalized traits is a central question in evolutionary biology. Natural variatio... more The evolution of canalized traits is a central question in evolutionary biology. Natural variation in highly conserved traits can provide clues about their evolutionary potential. Here we investigate natural variation in a conserved trait-even-skipped (eve) expression at the cellular blastoderm stage of embryonic development in Drosophila melanogaster. Expression of the pair-rule gene eve was quantitatively measured in three inbred lines derived from a natural population of D. melanogaster. One line showed marked differences in the spacing, amplitude and timing of formation of the characteristic seven-striped pattern over a fifty-minute period prior to the onset of gastrulation. Stripe 5 amplitude and the width of the interstripe between stripes 4 and 5 were both reduced in this line, while the interstripe distance between stripes 3 and 4 was increased. Engrailed expression in stage 10 embryos revealed a statistically significant increase in the length of parasegment 6 and a decrease in the length of parasegments 8 and 9. These changes are larger than those previously reported between D. melanogaster and D. pseudoobscura, two species that are thought to have diverged from a common ancestor over 25 million years ago. This line harbors a rare 448bp deletion in the first intron of knirps (kni). This finding suggested that reduced Kni levels caused the deviant eve expression, and indeed we observed lower levels of Kni protein at early cycle 14A in L2 compared to the other two lines. A second of the three lines displayed an approximately 20% greater level of expression for all seven eve stripes. The three lines are each viable and fertile, and none display a segmentation defect as adults, suggesting that early-acting variation in eve expression is ameliorated by developmental buffering mechanisms acting later in development. Canalization of the segmentation pathway may reduce the fitness consequences of genetic variation, thus allowing the persistence of mutations with unexpectedly strong gene expression phenotypes.

eLife, Sep 15, 2021

Although studies of Saccharomyces cerevisiae have provided many insights into mutagenesis and DNA... more Although studies of Saccharomyces cerevisiae have provided many insights into mutagenesis and DNA repair, most of this work has focused on a few laboratory strains. Much less is known about the phenotypic effects of natural variation within S. cerevisiae's DNA repair pathways. Here, we use natural polymorphisms to detect historical mutation spectrum differences among several wild and domesticated S. cerevisiae strains. To determine whether these differences are likely caused by genetic mutation rate modifiers, we use a modified fluctuation assay with a CAN1 reporter to measure de novo mutation rates and spectra in 16 of the analyzed strains. We measure a 10-fold range of mutation rates and identify two strains with distinctive mutation spectra. These strains, known as AEQ and AAR, come from the panel's 'Mosaic beer' clade and share an enrichment for C > A mutations that is also observed in rare variation segregating throughout the genomes of several Mosaic beer and Mixed origin strains. Both AEQ and AAR are haploid derivatives of the diploid natural isolate CBS 1782, whose rare polymorphisms are enriched for C > A as well, suggesting that the underlying mutator allele is likely active in nature. We use a plasmid complementation test to show that AAR and AEQ share a mutator allele in the DNA repair gene OGG1, which excises 8-oxoguanine lesions that can cause C > A mutations if left unrepaired.

We study the transition time between different metastable states in the continuous Wright-Fisher ... more We study the transition time between different metastable states in the continuous Wright-Fisher (diffusion) model. We construct an adaptive landscape for describing the system both qualitatively and quantitatively. When strong genetic drift and weak mutation generate infinite adaptive peaks, we calculate the expected time to escape from such peak states. We find a new way to analytically approximate the escape time, which extends the application of Kramer's classical formulae to the cases of non-Gaussian equilibrium distribution and bridges previous results in two limits. Our adaptive landscape, compared to the classical fitness landscape or other scalar functions, is directly related to system's middle-and-long-term dynamics and is self-consistent in the whole parameter space. Our work provides a complete description for the bi-stabilities in the present model.

bioRxiv (Cold Spring Harbor Laboratory), Sep 27, 2021

Developmental robustness (canalization) is a common attribute of traits in multi-cellular organis... more Developmental robustness (canalization) is a common attribute of traits in multi-cellular organisms. High robustness ensures the reproducibility of phenotypes in the face of environmental and developmental noise, but it also dampens the expression of genetic mutation, the fuel for adaptive evolution. A reduction in robustness may therefore be adaptive under certain evolutionary scenarios. To better understand how robustness influences phenotypic evolution, and to decipher conditions under which canalization itself evolves, a genetic model was constructed in which phenotype is explicitly represented as a collection of traits, calculated from genotype, and the degree of robustness can be explicitly controlled. The genes were subjected to mutation, altering phenotype and fitness. We then simulated the dynamics of a population evolving under two classes of initial conditions, one in which the population is at a fitness optimum and one in which it is far away. The model is formulated with two robustness parameters in the genotype to phenotype map, controlling robustness over a tight (γ) or a broad (α) range of values. Within the robustness range determined by γ, high robustness results in a equilibrium population fitness closer to the optimal fitness value than low robustness. High robustness should be favored, therefore, under a constant optimal environment. This situation reverses when populations are challenged to evolve to a new phenotype optimum. In this situation, low robustness populations adapt faster than high robustness populations and reach higher equilibrium mean fitness. A larger set of phenotypes are accessable by mutation when robustness is low, in part explaining why low robustness is favored under this condition. A larger range of robustness could be sampled by varying α, revealing a complex relationship between robustness and both the initial rate of phenotypic adaptation as well as the final equilibrium population mean fitness. Intermediate values of α produced a bifurcation in evolutionary trajectories, with some populations remaining at low population mean fitness, and others escaping to achieve high population mean fitness. We then allowed robustness itself to be encoded by a mutable genetic locus that could co-evolve along with the phenotype under selection. Low robustness genotypes are initially favored 2. CC-BY-NC-ND 4.

Studying the genetic and molecular characteristics of brewing yeast strains is crucial for unders... more Studying the genetic and molecular characteristics of brewing yeast strains is crucial for understanding their domestication history and adaptations accumulated over time in fermentation environments, and for guiding optimizations to the brewing process itself. Saccharomyces cerevisiae (brewing yeast) is amongst the most profiled organisms on the planet, yet the temporal molecular changes that underlie industrial fermentation and beer brewing remain understudied. Here, we characterized the genomic makeup of a Saccharomyces cerevisiae ale yeast widely used in the production of Hefeweizen beers, and applied shotgun mass spectrometry to systematically measure the proteomic changes throughout two fermentation cycles which were separated by 14 rounds of serial repitching. The resulting brewing yeast proteomics resource includes 64,740 protein abundance measurements. We found that this strain possesses typical genetic characteristics of Saccharomyces cerevisiae ale strains and displayed p...

Developmental robustness (canalization) is a common attribute of traits in multi-cellular organis... more Developmental robustness (canalization) is a common attribute of traits in multi-cellular organisms. High robustness ensures the reproducibility of phenotypes in the face of environmental and developmental noise, but it also dampens the expression of genetic mutation, the fuel for adaptive evolution. A reduction in robustness may therefore be adaptive under certain evolutionary scenarios. To better understand how robustness influences phenotypic evolution, and to decipher conditions under which canalization itself evolves, a genetic model was constructed in which phenotype is explicitly represented as a collection of traits, calculated from genotype, and the degree of robustness can be explicitly controlled. The genes were subjected to mutation, altering phenotype and fitness. We then simulated the dynamics of a population evolving under two classes of initial conditions, one in which the population is at a fitness optimum and one in which it is far away. The model is formulated with two robustness parameters in the genotype to phenotype map, controlling robustness over a tight (γ) or a broad (α) range of values. Within the robustness range determined by γ, high robustness results in a equilibrium population fitness closer to the optimal fitness value than low robustness. High robustness should be favored, therefore, under a constant optimal environment. This situation reverses when populations are challenged to evolve to a new phenotype optimum. In this situation, low robustness populations adapt faster than high robustness populations and reach higher equilibrium mean fitness. A larger set of phenotypes are accessable by mutation when robustness is low, in part explaining why low robustness is favored under this condition. A larger range of robustness could be sampled by varying α, revealing a complex relationship between robustness and both the initial rate of phenotypic adaptation as well as the final equilibrium population mean fitness. Intermediate values of α produced a bifurcation in evolutionary trajectories, with some populations remaining at low population mean fitness, and others escaping to achieve high population mean fitness. We then allowed robustness itself to be encoded by a mutable genetic locus that could co-evolve along with the phenotype under selection. Low robustness genotypes are initially favored 2. CC-BY-NC-ND 4.

Journal of Evolutionary Biology

Canalization involves mutational robustness, the lack of phenotypic change as a result of genetic... more Canalization involves mutational robustness, the lack of phenotypic change as a result of genetic mutations. Given the large divergence in phenotype across species, understanding the relationship between high robustness and evolvability has been of interest to both theorists and experimentalists. Although canalization was originally proposed in the context of multicellular organisms, the effect of multicellularity and other classes of hierarchical organization on evolvability has not been considered by theoreticians. We address this issue using a Boolean population model with explicit representation of an environment in which individuals with explicit genotype and a hierarchical phenotype representing multicellularity evolve. Robustness is described by a single real number between zero and one which emerges from the genotype–phenotype map. We find that high robustness is favoured in constant environments, and lower robustness is favoured after environmental change. Multicellularity ...

Current Opinion in Genetics & Development

bioRxiv, Sep 27, 2021

Developmental robustness (canalization) is a common attribute of traits in multi-cellular organis... more Developmental robustness (canalization) is a common attribute of traits in multi-cellular organisms. High robustness ensures the reproducibility of phenotypes in the face of environmental and developmental noise, but it also dampens the expression of genetic mutation, the fuel for adaptive evolution. A reduction in robustness may therefore be adaptive under certain evolutionary scenarios. To better understand how robustness influences phenotypic evolution, and to decipher conditions under which canalization itself evolves, a genetic model was constructed in which phenotype is explicitly represented as a collection of traits, calculated from genotype, and the degree of robustness can be explicitly controlled. The genes were subjected to mutation, altering phenotype and fitness. We then simulated the dynamics of a population evolving under two classes of initial conditions, one in which the population is at a fitness optimum and one in which it is far away. The model is formulated with two robustness parameters in the genotype to phenotype map, controlling robustness over a tight (γ) or a broad (α) range of values. Within the robustness range determined by γ, high robustness results in a equilibrium population fitness closer to the optimal fitness value than low robustness. High robustness should be favored, therefore, under a constant optimal environment. This situation reverses when populations are challenged to evolve to a new phenotype optimum. In this situation, low robustness populations adapt faster than high robustness populations and reach higher equilibrium mean fitness. A larger set of phenotypes are accessable by mutation when robustness is low, in part explaining why low robustness is favored under this condition. A larger range of robustness could be sampled by varying α, revealing a complex relationship between robustness and both the initial rate of phenotypic adaptation as well as the final equilibrium population mean fitness. Intermediate values of α produced a bifurcation in evolutionary trajectories, with some populations remaining at low population mean fitness, and others escaping to achieve high population mean fitness. We then allowed robustness itself to be encoded by a mutable genetic locus that could co-evolve along with the phenotype under selection. Low robustness genotypes are initially favored 2. CC-BY-NC-ND 4.