RESUMEN
tRNA modifications are crucial in all organisms to ensure tRNA folding and stability, and accurate translation. In both the yeast Saccharomyces cerevisiae and the evolutionarily distant yeast Schizosaccharomyces pombe, mutants lacking certain tRNA body modifications (outside the anticodon loop) are temperature sensitive due to rapid tRNA decay (RTD) of a subset of hypomodified tRNAs. Here we show that for each of two S. pombe mutants subject to RTD, mutations in ribosomal protein genes suppress the temperature sensitivity without altering tRNA levels. Prior work showed that S. pombe trm8Δ mutants, lacking 7-methylguanosine, were temperature sensitive due to RTD, and that one class of suppressors had mutations in the general amino acid control (GAAC) pathway, which was activated concomitant with RTD, resulting in further tRNA loss. We now find that another class of S. pombe trm8Δ suppressors have mutations in rpl genes, encoding 60S subunit proteins, and that suppression occurs with minimal restoration of tRNA levels and reduced GAAC activation. Furthermore, trm8Δ suppression extends to other mutations in the large or small ribosomal subunit. We also find that S. pombe tan1Δ mutants, lacking 4-acetylcytidine, are temperature sensitive due to RTD, that one class of suppressors have rpl mutations, associated with minimal restoration of tRNA levels, and that suppression extends to other rpl and rps mutations. However, although S. pombe tan1Δ temperature sensitivity is associated with some GAAC activation, suppression by an rpl mutation only modestly inhibits GAAC activation. We propose a model in which ribosomal protein mutations result in reduced ribosome concentrations, leading to both reduced ribosome collisions and a reduced requirement for tRNA, with these effects having different relative importance in trm8Δ and tan1Δ mutants. This model is consistent with our results in S. cerevisiae trm8Δ trm4Δ mutants, known to undergo RTD, fueling speculation that this model applies across eukaryotes.
Asunto(s)
Saccharomyces cerevisiae , Schizosaccharomyces , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , ARN de Transferencia/genética , ARN de Transferencia/metabolismo , Procesamiento Postranscripcional del ARN , Schizosaccharomyces/genética , Schizosaccharomyces/metabolismo , Ribosomas/genética , Ribosomas/metabolismo , Proteínas Ribosómicas/genética , MutaciónRESUMEN
After a COVID-related hiatus, the fifth biennial symposium on Evolution and Core Processes in Gene Regulation met at the Stowers Institute in Kansas City, Missouri July 21 to 24, 2022. This symposium, sponsored by the American Society for Biochemistry and Molecular Biology (ASBMB), featured experts in gene regulation and evolutionary biology. Topic areas covered enhancer evolution, the cis-regulatory code, and regulatory variation, with an overall focus on bringing the power of deep learning (DL) to decipher DNA sequence information. DL is a machine learning method that uses neural networks to learn complex rules that make predictions about diverse types of data. When DL models are trained to predict genomic data from DNA sequence information, their high prediction accuracy allows the identification of impactful genetic variants within and across species. In addition, the learned sequence rules can be extracted from the model and provide important clues about the mechanistic underpinnings of the cis-regulatory code.
Asunto(s)
COVID-19 , Aprendizaje Profundo , Humanos , Genómica , Redes Neurales de la Computación , Expresión GénicaRESUMEN
The distribution of recombination events along large cereal chromosomes is uneven and is generally restricted to gene-rich telomeric ends. To understand how the lack of recombination affects diversity in the large pericentromeric regions, we analysed deep exome capture data from a final panel of 815 Hordeum vulgare (barley) cultivars, landraces and wild barleys, sampled from across their eco-geographical ranges. We defined and compared variant data across the pericentromeric and non-pericentromeric regions, observing a clear partitioning of diversity both within and between chromosomes and germplasm groups. Dramatically reduced diversity was found in the pericentromeres of both cultivars and landraces when compared with wild barley. We observed a mixture of completely and partially differentiated single-nucleotide polymorphisms (SNPs) between domesticated and wild gene pools, suggesting that domesticated gene pools were derived from multiple wild ancestors. Patterns of genome-wide linkage disequilibrium, haplotype block size and number, and variant frequency within blocks showed clear contrasts among individual chromosomes and between cultivars and wild barleys. Although most cultivar chromosomes shared a single major pericentromeric haplotype, chromosome 7H clearly differentiated the two-row and six-row types associated with different geographical origins. Within the pericentromeric regions we identified 22 387 non-synonymous SNPs, 92 of which were fixed for alternative alleles in cultivar versus wild accessions. Surprisingly, only 29 SNPs found exclusively in the cultivars were predicted to be 'highly deleterious'. Overall, our data reveal an unconventional pericentromeric genetic landscape among distinct barley gene pools, with different evolutionary processes driving domestication and diversification.
Asunto(s)
Hordeum , Cromosomas , Domesticación , Hordeum/genética , Desequilibrio de Ligamiento/genéticaRESUMEN
Strains of Saccharomyces cerevisiae used to make beer, bread, and wine are genetically and phenotypically distinct from wild populations associated with trees. The origins of these domesticated populations are not always clear; human-associated migration and admixture with wild populations have had a strong impact on S. cerevisiae population structure. We examined the population genetic history of beer strains and found that ale strains and the S. cerevisiae portion of allotetraploid lager strains were derived from admixture between populations closely related to European grape wine strains and Asian rice wine strains. Similar to both lager and baking strains, ale strains are polyploid, providing them with a passive means of remaining isolated from other populations and providing us with a living relic of their ancestral hybridization. To reconstruct their polyploid origin, we phased the genomes of two ale strains and found ale haplotypes to both be recombinants between European and Asian alleles and to also contain novel alleles derived from extinct or as yet uncharacterized populations. We conclude that modern beer strains are the product of a historical melting pot of fermentation technology.
Asunto(s)
Poliploidía , Saccharomyces cerevisiae/genética , Asia , Cerveza , Europa (Continente) , Fermentación/fisiología , Haplotipos/genética , Saccharomyces cerevisiae/clasificación , VinoRESUMEN
BACKGROUND: The composition of bacteria within the vaginal microbiome has garnered a lot of recent attention and has been associated with reproductive health and disease. Despite the common occurrence of yeast (primarily Candida) within the vaginal microbiome, there is still an incomplete picture of relationships between yeast and bacteria (especially lactobacilli), as well as how such associations are governed. Such relationships could be important to a more holistic understanding of the vaginal microbiome and its connection to reproductive health. OBJECTIVE: The objective of the study was to perform molecular characterization of clinical specimens to define associations between vaginal bacteria (especially Lactobacillus species) and Candida colonization. In vitro studies were conducted to test the 2 most common dominant Lactobacillus species (Lactobacillus crispatus and Lactobacillus iners) in their ability to inhibit Candida growth and to examine the basis for such inhibition. STUDY DESIGN: A nested cross-sectional study of reproductive-age women from the Contraceptive CHOICE Project was conducted. Vaginal swabs from 299 women were selected to balance race and bacterial vaginosis status, resulting in a similar representation of black and white women in each of the 3 Nugent score categories (normal [0-3], intermediate [4-6], and bacterial vaginosis [7-10]). Sequencing of the 16S ribosomal gene (V4 region) was used to determine the dominant Lactobacillus species present (primarily Lactobacillus iners and Lactobacillus crispatus), defined as >50% of the community. Subjects without dominance by a single Lactobacillus species were classified as Diverse. A Candida-specific quantitative polymerase chain reaction targeting the internally transcribed spacer 1 was validated using vaginal samples collected from a second cohort of women and used to assess Candida colonization. Two hundred fifty-five nonpregnant women with sufficient bacterial biomass for analysis were included in the final analysis. Generalized linear models were used to evaluate associations between Lactobacillus dominance, sociodemographic and risk characteristics, and vaginal Candida colonization. In separate in vitro studies, the potential of cell-free supernatants from Lactobacillus crispatus and Lactobacillus iners cultures to inhibit Candida growth was evaluated. RESULTS: Forty-two women (16%) were vaginally colonized with Candida. Microbiomes characterized as Diverse (38%), Lactobacillus iners-dominant (39%), and Lactobacillus crispatus-dominant (20%) were the most common. The microbiome, race, and Candida colonization co-varied with a higher prevalence of Candida among black women and Lactobacillus iners-dominant communities compared with white women and Lactobacillus crispatus-dominant communities. Lactobacillus iners-dominant communities were more likely to harbor Candida than Lactobacillus crispatus-dominant communities (odds ratio, 2.85, 95% confidence interval, 1.03-7.21; Fisher exact test, P = .048). In vitro, Lactobacillus crispatus produced greater concentrations of lactic acid and exhibited significantly more pH-dependent growth inhibition of Candida albicans, suggesting a potential mechanism for the clinical observations. CONCLUSION: In nonpregnant women, Lactobacillus iners-dominant communities were significantly more likely to harbor Candida than Lactobacillus crispatus-dominant communities, suggesting that Lactobacillus species have different relationships with Candida. In vitro experiments indicate that Lactobacillus crispatus may impede Candida colonization more effectively than Lactobacillus iners through a greater production of lactic acid.
Asunto(s)
Candida , Lactobacillus crispatus , Microbiota , Vagina/microbiología , Adolescente , Adulto , Estudios Transversales , Femenino , Humanos , Adulto JovenRESUMEN
Preterm birth affects approximately 1 out of every 10 births in the United States, leading to high rates of mortality and long-term negative health consequences. To investigate the mechanisms leading to preterm birth so as to develop prevention strategies, researchers have developed numerous mouse models of preterm birth. However, the lack of standard definitions for preterm birth in mice limits our field's ability to compare models and make inferences about preterm birth in humans. In this review, we discuss numerous mouse preterm birth models, propose guidelines for experiments and reporting, and suggest markers that can be used to assess whether pups are premature or mature. We argue that adoption of these recommendations will enhance the utility of mice as models for preterm birth.
Asunto(s)
Trabajo de Parto Prematuro/fisiopatología , Animales , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , EmbarazoRESUMEN
The genetic improvement of winemaking yeasts is a virtually infinite process, as the design of new strains must always cope with varied and ever-evolving production contexts. Good wine yeasts must feature both good primary traits, which are related to the overall fermentative fitness of the strain, and secondary traits, which provide accessory features augmenting its technological value. In this context, the superiority of "blind," genetic improvement techniques, as those based on the direct selection of the desired phenotype without prior knowledge of the genotype, was widely proven. Blind techniques such as adaptive evolution strategies were implemented for the enhancement of many traits of interest in the winemaking field. However, these strategies usually focus on single traits: this possibly leads to genetic tradeoff phenomena, where the selection of enhanced secondary traits might lead to sub-optimal primary fermentation traits. To circumvent this phenomenon, we applied a multi-step and strongly directed genetic improvement strategy aimed at combining a strong fermentative aptitude (primary trait) with an enhanced production of glutathione (secondary trait). We exploited the random genetic recombination associated to a library of 69 monosporic clones of strain UMCC 855 (Saccharomyces cerevisiae) to search for new candidates possessing both traits. This was achieved by consecutively applying three directional selective criteria: molybdate resistance (1), fermentative aptitude (2), and glutathione production (3). The strategy brought to the selection of strain 21T2-D58, which produces a high concentration of glutathione, comparable to that of other glutathione high-producers, still with a much greater fermentative aptitude.
Asunto(s)
Glutatión/metabolismo , Saccharomyces cerevisiae/metabolismo , Vino/microbiología , Fermentación , Genotipo , Molibdeno/metabolismo , Fenotipo , Filogenia , Saccharomyces cerevisiae/clasificación , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crecimiento & desarrollo , Vino/análisisRESUMEN
Qualitative patterns of gene activation and repression are often conserved despite an abundance of quantitative variation in expression levels within and between species. A major challenge to interpreting patterns of expression divergence is knowing which changes in gene expression affect fitness. To characterize the fitness effects of gene expression divergence, we placed orthologous promoters from eight yeast species upstream of malate synthase (MLS1) in Saccharomyces cerevisiae As expected, we found these promoters varied in their expression level under activated and repressed conditions as well as in their dynamic response following loss of glucose repression. Despite these differences, only a single promoter driving near basal levels of expression caused a detectable loss of fitness. We conclude that the MLS1 promoter lies on a fitness plateau whereby even large changes in gene expression can be tolerated without a substantial loss of fitness.
Asunto(s)
Regulación Fúngica de la Expresión Génica , Aptitud Genética , Malato Sintasa/genética , Saccharomyces cerevisiae/genética , ADN de Hongos/genética , Evolución Molecular , Genes Fúngicos , Malato Sintasa/biosíntesis , Regiones Promotoras Genéticas , Saccharomyces cerevisiae/enzimología , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/biosíntesis , Proteínas de Saccharomyces cerevisiae/genética , Factores de Transcripción/genética , Activación TranscripcionalRESUMEN
Populations continually incur new mutations with fitness effects ranging from lethal to adaptive. While the distribution of fitness effects of new mutations is not directly observable, many mutations likely either have no effect on organismal fitness or are deleterious. Historically, it has been hypothesized that a population may carry many mildly deleterious variants as segregating variation, which reduces the mean absolute fitness of the population. Recent advances in sequencing technology and sequence conservation-based metrics for inferring the functional effect of a variant permit examination of the persistence of deleterious variants in populations. The issue of segregating deleterious variation is particularly important for crop improvement, because the demographic history of domestication and breeding allows deleterious variants to persist and reach moderate frequency, potentially reducing crop productivity. In this study, we use exome resequencing of 15 barley accessions and genome resequencing of 8 soybean accessions to investigate the prevalence of deleterious single nucleotide polymorphisms (SNPs) in the protein-coding regions of the genomes of two crops. We conclude that individual cultivars carry hundreds of deleterious SNPs on average, and that nonsense variants make up a minority of deleterious SNPs. Our approach identifies known phenotype-altering variants as deleterious more frequently than the genome-wide average, suggesting that putatively deleterious variants are likely to affect phenotypic variation. We also report the implementation of a SNP annotation tool BAD_Mutations that makes use of a likelihood ratio test based on alignment of all currently publicly available Angiosperm genomes.
Asunto(s)
Sustitución de Aminoácidos , Biología Computacional/métodos , Productos Agrícolas/genética , Aptitud Genética , Glycine max/genética , Hordeum/genética , Mapeo Cromosómico/métodos , Evolución Molecular , Frecuencia de los Genes , Variación Genética , Genoma de Planta , Mutación , Tasa de Mutación , Fitomejoramiento , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADN/métodosRESUMEN
St. Louis and its famous Gateway Arch were the setting of the Special Symposium: Evolution and Core Processes in Gene Regulation, sponsored by the American Society for Biochemistry and Molecular Biology. Biochemists and evolutionary biologists highlighted growing connections between studies of biochemical mechanism and natural selection on gene expression.
Asunto(s)
Investigación Biomédica/tendencias , Evolución Molecular , Regulación de la Expresión Génica , Animales , Bioquímica , Congresos como Asunto , Código Genético , Humanos , Missouri , Biología Molecular , Recursos HumanosRESUMEN
Microbial contamination of cell culture is a major problem encountered both in academic labs and in the biotechnology/pharmaceutical industries. A broad spectrum of microbes including mycoplasma, bacteria, fungi, and viruses are the causative agents of cell culture contamination. Unfortunately, the existing disinfection techniques lack selectivity and/or lead to the development of drug-resistance, and more importantly there is no universal method to address all microbes. Here, we report a novel, chemical-free visible ultrashort pulsed laser method for cell culture disinfection. The ultrashort pulsed laser technology inactivates pathogens with mechanical means, a paradigm shift from the traditional pharmaceutical and chemical approaches. We demonstrate that ultrashort pulsed laser treatment can efficiently inactivate mycoplasma, bacteria, yeast, and viruses with good preservation of mammalian cell viability. Our results indicate that this ultrashort pulsed laser technology has the potential to serve as a universal method for the disinfection of cell culture.
RESUMEN
BACKGROUND: The laboratory mouse is the most commonly used model for studying variation in complex traits relevant to human disease. Here we present the whole-genome sequences of two inbred strains, LG/J and SM/J, which are frequently used to study variation in complex traits as diverse as aging, bone-growth, adiposity, maternal behavior, and methamphetamine sensitivity. RESULTS: We identified small nucleotide variants (SNVs) and structural variants (SVs) in the LG/J and SM/J strains relative to the reference genome and discovered novel variants in these two strains by comparing their sequences to other mouse genomes. We find that 39% of the LG/J and SM/J genomes are identical-by-descent (IBD). We characterized amino-acid changing mutations using three algorithms: LRT, PolyPhen-2 and SIFT. We also identified polymorphisms between LG/J and SM/J that fall in regulatory regions and highly informative transcription factor binding sites (TFBS). We intersected these functional predictions with quantitative trait loci (QTL) mapped in advanced intercrosses of these two strains. We find that QTL are both over-represented in non-IBD regions and highly enriched for variants predicted to have a functional impact. Variants in QTL associated with metabolic (231 QTL identified in an F16 generation) and developmental (41 QTL identified in an F34 generation) traits were interrogated and we highlight candidate quantitative trait genes (QTG) and nucleotides (QTN) in a QTL on chr13 associated with variation in basal glucose levels and in a QTL on chr6 associated with variation in tibia length. CONCLUSIONS: We show how integrating genomic sequence with QTL reduces the QTL search space and helps researchers prioritize candidate genes and nucleotides for experimental follow-up. Additionally, given the LG/J and SM/J phylogenetic context among inbred strains, these data contribute important information to the genomic landscape of the laboratory mouse.
Asunto(s)
Genoma , Ratones Endogámicos/genética , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Análisis de Secuencia de ADN/métodos , Algoritmos , Animales , Modelos Animales de Enfermedad , Evolución Molecular , Variación Genética , Ratones , FilogeniaRESUMEN
Regulatory changes rapidly accumulate between species, and interspecific hybrids often misexpress genes. Hybrid misexpression, expression levels outside the range of both parental species, can result from cis- and trans-acting regulatory changes that interact abnormally in hybrids. Thus, misexpressed genes may contribute to hybrid sterility. However, in the context of a whole organism, misexpression may not result directly from cis-trans interactions but rather indirectly from differences between hybrid and parental abundance of cell types. Here we eliminate the confounding effects of cell types by examining gene expression in a sterile interspecific yeast hybrid during meiosis. We investigated gene expression of the yeasts Saccharomyces cerevisiae, S. paradoxus, and their hybrid at multiple meiotic stages. Although the hybrid and parents exhibit similar changes in expression levels across meiosis, the hybrid meiotic program occurs earlier than either parent. The timing change produces a heterochronic pattern of misexpression during midmeiosis. Coincident with the timing of misexpression, we find a transition from predominantly trans-acting to cis-acting expression divergence and an increase in the number of opposing cis-trans changes. However, we find no direct relationship between opposing cis-trans changes and misexpression. Contrary to the notion that cis-trans interactions cause misexpression, a heterochronic shift in the normal meiotic gene expression program produces patterns of misexpression in an yeast hybrid. Our results imply that temporal dynamics of single cell types is important to understanding hybrid misexpression and its relationship to cis-trans interactions.
Asunto(s)
Meiosis , Saccharomyces/crecimiento & desarrollo , Saccharomyces/genética , Regulación Fúngica de la Expresión Génica , Genes Fúngicos , Especiación Genética , Hibridación Genética , Saccharomyces/clasificación , Especificidad de la EspecieRESUMEN
Changes in gene expression are commonly observed during evolution. However, the phenotypic consequences of expression divergence are frequently unknown and difficult to measure. Transcriptional regulators provide a mechanism by which phenotypic divergence can occur through multiple, coordinated changes in gene expression during development or in response to environmental changes. Yet, some changes in transcriptional regulators may be constrained by their pleiotropic effects on gene expression. Here, we use a genome-wide screen for promoters that are likely to have diverged in function and identify a yeast transcription factor, FZF1, that has evolved substantial differences in its ability to confer resistance to sulfites. Chimeric alleles from four Saccharomyces species show that divergence in FZF1 activity is due to changes in both its coding and upstream noncoding sequence. Between the two closest species, noncoding changes affect the expression of FZF1, whereas coding changes affect the expression of SSU1, a sulfite efflux pump activated by FZF1. Both coding and noncoding changes also affect the expression of many other genes. Our results show how divergence in the coding and promoter region of a transcription factor alters the response to an environmental stress.
Asunto(s)
Proteínas de Transporte de Anión/genética , Regulación Fúngica de la Expresión Génica , Proteínas de Saccharomyces cerevisiae/genética , Sulfitos , Factores de Transcripción/genética , Alelos , Proteínas de Transporte de Anión/metabolismo , Resistencia a Medicamentos/genética , Evolución Molecular , Regulación Fúngica de la Expresión Génica/efectos de los fármacos , Regulación Fúngica de la Expresión Génica/genética , Estudios de Asociación Genética , Genoma Fúngico , Sistemas de Lectura Abierta , Regiones Promotoras Genéticas , Secuencias Reguladoras de Ácidos Nucleicos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Especificidad de la Especie , Sulfitos/metabolismo , Sulfitos/farmacología , Factores de Transcripción/metabolismoRESUMEN
The abundance of genome polymorphism and divergence data has provided unprecedented insight into how mutation, drift and natural selection shape genome evolution. Application of the McDonald-Kreitman (MK) test to such data indicates a pervasive influence of positive selection, particularly in Drosophila species. However, evidence for positive selection in other species ranging from yeast to humans is often weak or absent. Although evidence for positive selection could be obscured in some species, there is also reason to believe that the frequency of adaptive substitutions could be overestimated as a result of epistatic fitness effects or hitchhiking of deleterious mutations. Based on these considerations it is argued that the common assumption of independence among sites must be relaxed before abandoning the neutral theory of molecular evolution.
Asunto(s)
Adaptación Biológica/genética , Evolución Molecular , Animales , Bacterias/genética , Drosophila/genética , Epistasis Genética , Aptitud Genética , Humanos , Modelos Genéticos , Mutación , Selección GenéticaRESUMEN
Deleterious mutations present a significant obstacle to adaptive evolution. Deleterious mutations can inhibit the spread of linked adaptive mutations through a population; conversely, adaptive substitutions can increase the frequency of linked deleterious mutations and even result in their fixation. To assess the impact of adaptive mutations on linked deleterious mutations, we examined the distribution of deleterious and neutral amino acid polymorphism in the human genome. Within genomic regions that show evidence of recent hitchhiking, we find fewer neutral but a similar number of deleterious SNPs compared to other genomic regions. The higher ratio of deleterious to neutral SNPs is consistent with simulated hitchhiking events and implies that positive selection eliminates some deleterious alleles and increases the frequency of others. The distribution of disease-associated alleles is also altered in hitchhiking regions. Disease alleles within hitchhiking regions have been associated with auto-immune disorders, metabolic diseases, cancers, and mental disorders. Our results suggest that positive selection has had a significant impact on deleterious polymorphism and may be partly responsible for the high frequency of certain human disease alleles.
Asunto(s)
Sustitución de Aminoácidos/genética , Enfermedades Autoinmunes/genética , Genoma Humano/genética , Trastornos Mentales/genética , Enfermedades Metabólicas/genética , Neoplasias/genética , Eliminación de Secuencia , Alelos , Evolución Molecular , Humanos , Polimorfismo de Nucleótido Simple , Selección GenéticaRESUMEN
Domesticated strains of Saccharomyces cerevisiae have adapted to resist copper and sulfite, two chemical stressors commonly used in winemaking. S. paradoxus, has not adapted to these chemicals despite being consistently present in sympatry with S. cerevisiae in vineyards. This contrast represents a case of apparent evolutionary constraints favoring greater adaptive capacity in S. cerevisiae. In this study, we used a comparative mutagenesis approach to test whether S. paradoxus is mutationally constrained with respect to acquiring greater copper and sulfite resistance. For both species, we assayed the rate, effect size, and pleiotropic costs of resistance mutations and sequenced a subset of 150 mutants isolated from our screen. We found that the distributions of mutational effects displayed by the two species were very similar and poorly explained the natural pattern. We also found that chromosome VIII aneuploidy and loss of function mutations in PMA1 confer copper resistance in both species, whereas loss of function mutations in REG1 were only a viable route to copper resistance in S. cerevisiae. We also observed a single de novo duplication of the CUP1 gene in S. paradoxus but none in S. cerevisiae. For sulfite, loss of function mutations in RTS1 and KSP1 confer resistance in both species, but mutations in RTS1 have larger average effects in S. paradoxus. Our results show that even when the distributions of mutational effects are largely similar, species can differ in the adaptive paths available to them. They also demonstrate that assays of the distribution of mutational effects may lack predictive insight concerning adaptive outcomes.
RESUMEN
Evolutionary compromises are thought to be common under fluctuating selection because the mutations that best enable adaptation to one environmental context can often be detrimental to others. Yet, prior experimental work has shown that generalists can sometimes perform as well as specialists in their own environments. Here we use a highly replicated evolutionary experiment (Nâ =â 448 asexual lineages of the brewer's yeast) to show that even though fluctuation between two environmental conditions often induces evolutionary compromises (at least early on), it can also help reveal difficult to reach adaptive outcomes that ultimately improve performance in both environments. Specifically, we begin by showing that yeast adaptation to chemical stress can involve fitness trade-offs with stress-free environments and that, accordingly, lineages that are repeatedly exposed to occasional stress tend to respond by trading performance for breadth of adaptation. We then show that on rare occasions, fluctuating selection leads to the evolution of no-cost generalists that can even outcompete constant selection specialists in their own environments. We propose that the discovery of these broader and more effective adaptive outcomes under fluctuating selection could be partially facilitated by changes in the adaptive landscape that result from having to deal with fitness trade-offs across different environmental conditions. Overall, our findings indicate that reconciling the short- and long-term evolutionary consequences of fluctuating selection could significantly improve our understanding of the evolution of specialization and generalism.
RESUMEN
Humans have had a significant impact on the distribution and abundance of Saccharomyces cerevisiae through its widespread use in beer, bread and wine production. Yet, similar to other Saccharomyces species, S. cerevisiae has also been isolated from habitats unrelated to fermentations. Strains of S. cerevisiae isolated from grapes, wine must and vineyards worldwide are genetically differentiated from strains isolated from oak-tree bark, exudate and associated soil in North America. However, the causes and consequences of this differentiation have not yet been resolved. Historical differentiation of these two groups may have been influenced by geographic, ecological or human-associated barriers to gene flow. Here, we make use of the relatively recent establishment of vineyards across North America to identify and characterize any active barriers to gene flow between these two groups. We examined S. cerevisiae strains isolated from grapes and oak trees within three North American vineyards and compared them to those isolated from oak trees outside of vineyards. Within vineyards, we found evidence of migration between grapes and oak trees and potential gene flow between the divergent oak-tree and vineyard groups. Yet, we found no vineyard genotypes on oak trees outside of vineyards. In contrast, Saccharomyces paradoxus isolated from the same sources showed population structure characterized by isolation by distance. The apparent absence of ecological or genetic barriers between sympatric vineyard and oak-tree populations of S. cerevisiae implies that vineyards play an important role in the mixing between these two groups.
Asunto(s)
ADN de Hongos/genética , Corteza de la Planta/microbiología , Saccharomyces cerevisiae/clasificación , Saccharomyces cerevisiae/genética , Vino/microbiología , Secuencia de Bases , Cerveza/microbiología , Pan/microbiología , Flujo Génico , Variación Genética , Genotipo , América del Norte , Filogenia , Quercus/microbiología , Saccharomyces cerevisiae/aislamiento & purificación , Alineación de Secuencia , Análisis de Secuencia de ADN , Microbiología del Suelo , Árboles/microbiologíaRESUMEN
A major goal in evolutionary biology is to understand how adaptive evolution has influenced natural variation, but identifying loci subject to positive selection has been a challenge. Here we present the adaptive loss of a pair of paralogous genes in specific Saccharomyces cerevisiae subpopulations. We mapped natural variation in freeze-thaw tolerance to two water transporters, AQY1 and AQY2, previously implicated in freeze-thaw survival. However, whereas freeze-thaw-tolerant strains harbor functional aquaporin genes, the set of sensitive strains lost aquaporin function at least 6 independent times. Several genomic signatures at AQY1 and/or AQY2 reveal low variation surrounding these loci within strains of the same haplotype, but high variation between strain groups. This is consistent with recent adaptive loss of aquaporins in subgroups of strains, leading to incipient balancing selection. We show that, although aquaporins are critical for surviving freeze-thaw stress, loss of both genes provides a major fitness advantage on high-sugar substrates common to many strains' natural niche. Strikingly, strains with non-functional alleles have also lost the ancestral requirement for aquaporins during spore formation. Thus, the antagonistic effect of aquaporin function-providing an advantage in freeze-thaw tolerance but a fitness defect for growth in high-sugar environments-contributes to the maintenance of both functional and nonfunctional alleles in S. cerevisiae. This work also shows that gene loss through multiple missense and nonsense mutations, hallmarks of pseudogenization presumed to emerge after loss of constraint, can arise through positive selection.