RESUMEN
Gene expression varies between individuals and corresponds to a key step linking genotypes to phenotypes. However, our knowledge regarding the species-wide genetic control of protein abundance, including its dependency on transcript levels, is very limited. Here, we have determined quantitative proteomes of a large population of 942 diverse natural Saccharomyces cerevisiae yeast isolates. We found that mRNA and protein abundances are weakly correlated at the population gene level. While the protein coexpression network recapitulates major biological functions, differential expression patterns reveal proteomic signatures related to specific populations. Comprehensive genetic association analyses highlight that genetic variants associated with variation in protein (pQTL) and transcript (eQTL) levels poorly overlap (3%). Our results demonstrate that transcriptome and proteome are governed by distinct genetic bases, likely explained by protein turnover. It also highlights the importance of integrating these different levels of gene expression to better understand the genotype-phenotype relationship.
Asunto(s)
Regulación Fúngica de la Expresión Génica , Proteoma , Sitios de Carácter Cuantitativo , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Transcriptoma , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteoma/genética , Proteoma/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Variación Genética , Proteómica/métodos , Genotipo , Fenotipo , Perfilación de la Expresión Génica/métodosRESUMEN
Gene expression is an essential step in the translation of genotypes into phenotypes. However, little is known about the transcriptome architecture and the underlying genetic effects at the species level. Here we generated and analyzed the pan-transcriptome of ~1,000 yeast natural isolates across 4,977 core and 1,468 accessory genes. We found that the accessory genome is an underappreciated driver of transcriptome divergence. Global gene expression patterns combined with population structure showed that variation in heritable expression mainly lies within subpopulation-specific signatures, for which accessory genes are overrepresented. Genome-wide association analyses consistently highlighted that accessory genes are associated with proportionally more variants with larger effect sizes, illustrating the critical role of the accessory genome on the transcriptional landscape within and between populations.
Asunto(s)
Regulación Fúngica de la Expresión Génica , Genoma Fúngico , Estudio de Asociación del Genoma Completo , Saccharomyces cerevisiae , Transcriptoma , Saccharomyces cerevisiae/genética , Variación Genética , Perfilación de la Expresión Génica/métodos , Genotipo , Polimorfismo de Nucleótido SimpleRESUMEN
RNA modifications are involved in numerous biological processes and are present in all RNA classes. These modifications can be constitutive or modulated in response to adaptive processes. RNA modifications play multiple functions since they can impact RNA base-pairings, recognition by proteins, decoding, as well as RNA structure and stability. However, their roles in stress, environmental adaptation and during infections caused by pathogenic bacteria have just started to be appreciated. With the development of modern technologies in mass spectrometry and deep sequencing, recent examples of modifications regulating host-pathogen interactions have been demonstrated. They show how RNA modifications can regulate immune responses, antibiotic resistance, expression of virulence genes, and bacterial persistence. Here, we illustrate some of these findings, and highlight the strategies used to characterize RNA modifications, and their potential for new therapeutic applications.