Biology subjects

Wittkopp, P.

Publications and source records attributed to Wittkopp, P..

8 recordsLinked to original sources

bioRxiv2026

Environmental impacts on gene expression noise and its relationship with fitness

Genetically identical cells grown in the same environment show variation in gene expression known as expression noise. Expression noise can be heritable and impact fitness, making it subject to natural selection. Increasing expression noise for the Saccharomyces cerevisiae TDH3 gene was shown to be beneficial in glucose-based media when mean TDH3 expression was far from the fitness optimum but deleterious when it was close to this optimum. Here, we show that growth on different carbon sources alters the effects of new mutations on TDH3 expression noise and examine the fitness effects of changing expression noise. In galactose-based media, we observed the same relationship between expression noise and fitness seen in glucose-based media, but in glycerol- and ethanol-based media, we observed the opposite relationship or no significant relationship, respectively. Using simulations of single-cell organisms, we found that these differences were most likely explained by environment-specific relationships between gene expression and fitness. We also found that, far from the optimum, the fitness effects of noise were greatest when expression was highly heritable between mother and daughter cells. The empirical observations and simulations reported in this study show how environments influence both the production of expression noise and its impacts on fitness.

evolutionary biology↗

bioRxiv2026

cis- and trans-regulatory factors contributing to divergent activity of the TDH3 promoter in Saccharomyces yeast

Changes in regulatory sequences controlling the timing and activity of gene products underlie much of natural phenotypic variation. Yet, what these changes are and how they impact gene expression remain largely unknown. To address this question, we investigated how transcriptional activity and homeostatic responsiveness of orthologous promoters of the metabolic gene TDH3 evolved among Saccharomyces yeast. We found that promoter expression level increased specifically in the S. cerevisiae lineage and that a substantial part of this increase was caused by genetic variants located between the well-characterized, conserved binding sites for two direct transcriptional regulators. These nucleotide changes altered the promoters expression levels while leaving the expression dynamics conserved. Further, the effects of these nucleotide changes were only seen in the presence of a third transcription factor, TYE7p, which is recruited by the other transcription factors through protein-protein interactions. These results suggest that the cis-regulatory changes act through their influence on the collective assembly/activation of the transcription factors, and that changes acting through such a mechanism can allow distinct parts of gene expression, such as expression level and dynamics, to be tuned separately.

genetics↗

bioRxiv2025

Epistatic impacts of cis- and trans-regulatory mutations on the distribution of mutational effects for gene expression in Saccharomyces cerevisiae

Epistasis can influence evolution by causing the distribution of phenotypic effects for new mutations to vary among genotypes. Here, we investigate how epistatic interactions between new mutations and an existing regulatory mutation might impact the evolution of gene expression using Saccharomyces cerevisiae. We do so by estimating the distribution of mutational effects for expression of a fluorescent reporter protein driven by the S. cerevisiae TDH3 promoter in a reference strain as well as in eight mutant strains. Each of the mutant strains differed from the reference strain by a single mutation affecting expression of the focal gene. We found that half of these regulatory mutations changed the variance and/or skewness of the distribution of mutational effects. A change in variance indicates a change in mutational robustness, and we found that one initial regulatory mutation increased mutational robustness while another decreased it. A change in skewness indicates a change in the relative frequency and/or effect size of mutations increasing or decreasing expression, and we found that the initial regulatory mutation in four strains had such an effect. Strikingly, in all four of these cases, the change in skewness increased the likelihood that new mutations would at least partially compensate for the effects of the initial regulatory mutation. If this form of epistatic impact on the distribution of mutational effects is common, it could provide a neutral mechanism reducing the divergence of gene expression and help explain the prevalence of alleles with compensatory effects in natural populations of S. cerevisiae.

evolutionary biology↗

bioRxiv2024

Plasticity and environment-specific relationships between gene expression and fitness in Saccharomyces cerevisiae

Phenotypic evolution is shaped by interactions between organisms and their environments. The environment influences how an organisms genotype determines its phenotype and how this phenotype affects its fitness. To better understand this dual role of the environment in the production and selection of phenotypic variation, we empirically determined and compared the genotype-phenotype-fitness relationship for mutant strains of the budding yeast Saccharomyces cerevisiae in four environments. Specifically, we measured how mutations in the promoter of the metabolic gene TDH3 modified its expression level and affected its growth on media with four different carbon sources. In each environment, we observed a clear relationship between TDH3 expression level and fitness, but this relationship differed among environments. Genetic variants with similar effects on TDH3 expression in different environments often had different effects on fitness and vice versa. Such environment-specific relationships between phenotype and fitness can shape the evolution of phenotypic plasticity. The set of mutants we examined also allowed us to compare the effects of mutations disrupting binding sites for key transcriptional regulators and the TATA box, which is part of the core promoter sequence. Mutations disrupting the binding sites for the transcription factors had more variable effects on expression among environments than mutations disrupting the TATA box, yet mutations with the most environmentally variable effects on fitness were located in the TATA box. This observation suggests that mutations affecting different molecular mechanisms are likely to contribute unequally to regulatory sequence evolution in changing environments. Significance StatementEnvironments can affect the phenotypic traits an organism produces as well as the adaptive value of these traits (i.e. whether those traits will allow the organism to better survive and pass their genes on to the next generation). This study shows how the environment impacts both the production and selection of traits using the expression of a metabolic gene in the bakers yeast as a model system. This study further shows that some types of genetic changes make gene expression traits more responsive to environmental changes than others, suggesting that genetic changes affecting different molecular mechanisms of gene regulation may contribute differently to genetic evolution.

evolutionary biology↗

bioRxiv2024

Divergence of Grainy head affects chromatin accessibility, gene expression, and embryonic viability in Drosophila melanogaster

Pioneer factors are critical for gene regulation and development because they bind chromatin and make DNA more accessible for binding by other transcription factors. The pioneer factor Grainy head (Grh) is present across metazoans and has been shown to retain a role in epithelium development in fruit flies, nematodes, and mice despite extensive divergence in both amino acid sequence and length. Here, we investigate the evolution of Grh function by comparing the effects of the fly (Drosophila melanogaster) and worm (Caenorhabditis elegans) Grh orthologs on chromatin accessibility, gene expression, embryonic development, and viability in transgenic D. melanogaster. We found that the Caenorhabditis elegans ortholog rescued cuticle development but not full embryonic viability in Drosophila melanogaster grh null mutants. At the molecular level, the C. elegans ortholog only partially rescued chromatin accessibility and gene expression. Divergence in the disordered N-terminus of the Grh protein contributes to these differences in embryonic viability and molecular phenotypes. These data show how pioneer factors can diverge in sequence and function at the molecular level while retaining conserved developmental functions at the organismal level. SUMMARY STATEMENTDespite divergence in a disordered region that affects function at both molecular and organismal levels, the Caenorhabditis elegans Grainy head (Grh) protein rescued cuticle morphology in D. melanogaster embryos.

developmental biology↗

bioRxiv2020

Distinct genetic architectures underlie divergent thorax, leg, and wing pigmentation between Drosophila elegans and D. gunungcola

Understanding the genetic basis of species differences is a major goal in evolutionary biology. Pigmentation divergence between Drosophila species often involves genetic changes in pigmentation candidate genes that pattern the body and wings, but it remains unclear how these changes affect pigmentation evolution in multiple body parts between the same diverging species. Drosophila elegans and D. gunungcola show pigmentation differences in the thorax, legs, and wings, with D. elegans exhibiting male-specific wing spots and D. gunungcola lacking wing spots with intensely dark thoraces and legs. Here, we performed QTL mapping to identify the genetic architecture of these differences. We find a large effect QTL on the X chromosome for all three body parts. QTL on Muller Element E were found for thorax pigmentation in both backcrosses but were only marginally significant in one backcross for the legs and wings. Consistent with this observation, we isolated the effects of the Muller Element E QTL by introgressing D. gunungcola alleles into a D. elegans genetic background and found that D. gunungcola alleles linked near the pigmentation candidate gene ebony caused intense darkening of the thorax, minimal darkening of legs, and minimal shrinking of wing spots. D. elegans ebony mutants showed changes in pigmentation consistent with Ebony having different effects on pigmentation in different tissues. Our results suggest that multiple genes have evolved differential effects on pigmentation levels in different body regions.

evolutionary biology↗

bioRxiv2020

Genetic architecture of a body color cline in Drosophila americana

Phenotypic variation within a species is often structured geographically in clines. In Drosophila americana, a longitudinal cline for body color exists within North America that appears to be due to local adaptation. The tan and ebony genes have been hypothesized to contribute to this cline, with alleles of both genes that lighten body color found in D. americana. These alleles are similar in sequence and function to the allele fixed in D. americanas more lightly pigmented sister species, Drosophila novamexicana. To test this hypothesis, we examined the frequency and geographic distribution of D. novamexicana-like alleles of tan and ebony in D. americana. Among alleles from over 100 strains of D. americana isolated from 21 geographic locations, we failed to identify additional alleles of tan or ebony with as much sequence similarity to D. novamexicana as the alleles previously described. However, using genetic analysis of 51 D. americana strains derived from 20 geographic locations, we identified one new allele of ebony and one new allele of tan segregating in D. americana that are functionally equivalent to the D. novamexicana allele. An additional 5 alleles of tan also showed marginal evidence of functional similarity. Given the rarity of these alleles, however, we conclude that they are unlikely to be driving the pigmentation cline. Indeed, phenotypic distributions of the 51 backcross populations analyzed indicate a more complex genetic architecture, with diversity in the number and effects of loci altering pigmentation observed both within and among populations of D. americana. This genetic heterogeneity poses a challenge to association studies and genomic scans for clinal variation, but might be common in natural populations.

evolutionary biology↗

bioRxiv2019

Co-evolving wing spots and mating displays are genetically separable traits in Drosophila

The evolution of sexual traits often involves correlated changes in morphology and behavior. For example, in Drosophila, divergent mating displays are often accompanied by divergent pigment patterns. To better understand how such traits co-evolve, we investigated the genetic basis of correlated divergence in wing pigmentation and mating display between the sibling species Drosophila elegans and D. gunungcola. Drosophila elegans males have an area of black pigment on their wings known as a wing spot and appear to display this spot to females by extending their wings laterally during courtship. By contrast, D. gunungcola lacks both of these traits. Using Multiplexed Shotgun Genotyping (MSG), we identified a [~]440 kb region on the X chromosome that behaves like a genetic switch controlling the presence or absence of male-specific wing spots. This region includes the candidate gene optomotor-blind (omb), which plays a critical role in patterning the Drosophila wing. The genetic basis of divergent wing display is more complex, with at least two loci on the X chromosome and two loci on autosomes contributing to its evolution. Introgressing the X-linked region affecting wing spot development from D. gunungcola into D. elegans reduced pigmentation in the wing spots but did not affect the wing display, indicating that these are genetically separable traits. Consistent with this observation, broader sampling of wild D. gunungcola populations confirmed the wing spot and wing display are evolving independently: some D. gunungcola males preformed wing displays similar to D. elegans despite lacking wing spots. These data suggest that correlated selection pressures rather than physical linkage or pleiotropy are responsible for the coevolution of these morphological and behavioral traits. They also suggest that the change in morphology evolved prior to the change in behavior.

evolutionary biology↗