RESUMO
Although evolution is driven by changes in how regulatory pathways control development, we know little about the molecular details underlying these transitions. The TRA-2 domain that mediates contact with TRA-1 is conserved in Caenorhabditis. By comparing the interaction of these proteins in two species, we identified a striking change in how sexual development is controlled. Identical mutations in this domain promote oogenesis in Caenorhabditis elegans but promote spermatogenesis in Caenorhabditis briggsae. Furthermore, the effects of these mutations involve the male-promoting gene fem-3 in C. elegans but are independent of fem-3 in C. briggsae. Finally, reciprocal mutations in these genes show that C. briggsae TRA-2 binds TRA-1 to prevent expression of spermatogenesis regulators. By contrast, in C. elegans TRA-1 sequesters TRA-2 in the germ line, allowing FEM-3 to initiate spermatogenesis. Thus, we propose that the flow of information within the sex determination pathway has switched directions during evolution. This result has important implications for how evolutionary change can occur.
Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Processos de Determinação Sexual , Espermatogênese , Animais , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Masculino , Espermatogênese/genética , Feminino , Caenorhabditis/genética , Evolução Biológica , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Mutação , Oogênese/genética , Evolução Molecular , Autofertilização , Proteínas de Ligação a DNA , Fatores de TranscriçãoRESUMO
Short ("seed") or extended base pairing between microRNAs (miRNAs) and their target RNAs enables post-transcriptional silencing in many organisms. These interactions allow the computational prediction of potential targets. In model organisms, predicted targets are frequently validated experimentally; hence meaningful miRNA-regulated processes are reported. However, in non-models, these reports mostly rely on computational prediction alone. Many times, further bioinformatic analyses such as Gene Ontology (GO) enrichment are based on these in silico projections. Here such approaches are reviewed, their caveats are highlighted and the ease of picking false targets from predicted lists is demonstrated. Discoveries that shed new light on how miRNAs evolved to regulate targets in various phyletic groups are discussed, in addition to the pitfalls of target identification in non-model organisms. The goal is to prevent the misuse of bioinformatic tools, as they cannot bypass the biological understanding of miRNA-target regulation.
Assuntos
Ontologia Genética , MicroRNAs/genética , Modelos Biológicos , Animais , Biologia Computacional , Humanos , MicroRNAs/metabolismo , FilogeniaRESUMO
The evolutionary modification of development was fundamental in generating extant plant diversity. Similarly, the modification of development is a path forward to engineering the plants of the future, provided we know enough about what to modify. Understanding how extant diversity was generated will reveal productive pathways forward for modifying development. Here, I discuss four examples of developmental pathways that have been remodeled by changes to protein-protein interactions. These are cases where changes to developmental pathways have been paralleled by recent changes, selected for or engineered by humans. Extant plant diversity represents a vast treasure trove of molecular solutions to ecological problems. Mining this treasure trove will allow for the intentional modification of plant development for solving future problems.
Assuntos
Evolução Biológica , Desenvolvimento Vegetal , Proteínas de Plantas/metabolismo , Mapeamento de Interação de Proteínas , Phytoplasma , Proteínas de Plantas/química , Transdução de SinaisRESUMO
Misregulation of gene expression is often observed in interspecific hybrids and is generally attributed to regulatory incompatibilities caused by divergence between the two genomes. However, it has been challenging to distinguish effects of regulatory divergence from secondary effects including developmental and physiological defects common to hybrids. Here, we use RNA-Seq to profile gene expression in F1 hybrid male larvae from crosses of Drosophila melanogaster to its sibling species D. simulans. We analyze lethal and viable hybrid males, the latter produced using a mutation in the X-linked D. melanogaster Hybrid male rescue (Hmr) gene and compare them with their parental species and to public data sets of gene expression across development. We find that Hmr has drastically different effects on the parental and hybrid genomes, demonstrating that hybrid incompatibility genes can exhibit novel properties in the hybrid genetic background. Additionally, we find that D. melanogaster alleles are preferentially affected between lethal and viable hybrids. We further determine that many of the differences between the hybrids result from developmental delay in the Hmr(+) hybrids. Finally, we find surprisingly modest expression differences in hybrids when compared with the parents, with only 9% and 4% of genes deviating from additivity or expressed outside of the parental range, respectively. Most of these differences can be attributed to developmental delay and differences in tissue types. Overall, our study suggests that hybrid gene misexpression is prone to overestimation and that even between species separated by approximately 2.5 Ma, regulatory incompatibilities are not widespread in hybrids.
Assuntos
Proteínas de Drosophila/genética , Drosophila/classificação , Drosophila/genética , Animais , Drosophila/fisiologia , Regulação da Expressão Gênica , Genes Letais , Genes Ligados ao Cromossomo X , Especiação Genética , Hibridização Genética , Masculino , Análise de Sequência de RNA , Especificidade da EspécieRESUMO
Hybridization and polyploidization are prominent processes in plant evolution. Hybrids and allopolyploids typically exhibit radically altered gene expression patterns relative to their parents, a phenomenon termed "transcriptomic shock." To distinguish the effects of hybridization from polyploidization on coregulation of divergent alleles, we analyzed expression of parental copies (homoeologs) of 11,608 genes using RNA-seq-based transcriptome profiling in reciprocal hybrids and tetraploids constructed from subspecies japonica and indica of Asian rice (Oryza sativa L.). The diploid hybrids and their derived allopolyploids differ dramatically in morphology, despite having the same suite of genes and genic proportions. Allelic and homoeolog-specific transcripts were unequivocally diagnosed in the hybrids and tetraploids based on parent-specific SNPs. Compared with the in silico hybrid (parental mix), the range of progenitor expression divergence was significantly reduced in both reciprocally generated F1 hybrids, presumably due to the ameliorating effects of a common trans environment on divergent cis-factors. In contrast, parental expression differences were greatly elaborated at the polyploid level, which we propose is a consequence of stoichiometric disruptions associated with the numerous chromosomal packaging and volumetric changes accompanying nascent polyploidy. We speculate that the emergent property of "whole genome doubling" has repercussions that reverberate throughout the transcriptome and downstream, ultimately generating altered phenotypes. This perspective may yield insight into the nature of adaptation and the origin of evolutionary novelty accompanying polyploidy.
Assuntos
Genoma de Planta , Oryza/genética , Poliploidia , Simulação por Computador , Evolução Molecular , Especiação Genética , Hibridização Genética , Cariótipo , Modelos Genéticos , Oryza/classificação , Fenótipo , Polimorfismo de Nucleotídeo Único , RNA de Plantas/genética , Especificidade da Espécie , TetraploidiaRESUMO
Epigenetic regulation varies with the environment. In the fruit fly Drosophila melanogaster, environmental temperature can affect chromatin-based gene regulation. Genes regulated by the Polycomb group can vary in their transcriptional output in response to changes in temperature, which typically increases with decreasing temperature. Here, we studied temperature-sensitive expression of Polycomb group target genes on a genome-wide scale, as well as temperature-sensitive enrichment of two histone modifications associated with the regulation of Polycomb group target genes, H3K27me3 and H3K4me3. We investigated temperature-sensitivity in adult flies, and possible differences thereof between populations adapted to temperate and tropical climates. Compared to genes not targeted by the Polycomb group, an elevated number of target genes showed higher expression at the lower temperature, as it is typically observed for Polycomb group regulation. Many of the Polycomb group target genes also exhibited temperature-sensitive H3K4me3 enrichment in the same direction, and the H3K4me3 temperature response correlated positively with that of expression. A small set of target sites also showed temperature-sensitive enrichment of H3K27me3, again with a higher proportion corresponding to increased transcriptional activation at the lower temperature. Overall, higher transcriptional activity at lower temperature was less pronounced in males compared to females, and in temperate compared to tropical flies. Possible trans- and cis-acting factors responsible for reduced expression plasticity in temperate flies were identified, including factors belonging to the Trithorax group and insulator binding proteins, respectively.
Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Animais , Masculino , Feminino , Drosophila melanogaster/metabolismo , Histonas/genética , Histonas/metabolismo , Epigênese Genética , Temperatura , Regulação da Expressão Gênica , Proteínas do Grupo Polycomb/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila/metabolismoRESUMO
Environmental temperature can affect chromatin-based gene regulation, in particular in ectotherms such as insects. Genes regulated by the Polycomb group (PcG) vary in their transcriptional output in response to changes in temperature. Expression of PcG-regulated genes typically increases with decreasing temperatures. Here, we examined variations in temperature-sensitive expression of PcG target genes in natural populations from different climates of Drosophila melanogaster, and differences thereof across different fly stages and tissues. Temperature-induced expression plasticity was found to be stage- and sex-specific with differences in the specificity between the examined PcG target genes. Some tissues and stages, however, showed a higher number of PcG target genes with temperature-sensitive expression than others. Overall, we found higher levels of temperature-induced expression plasticity in African tropical flies from the ancestral species range than in flies from temperate Europe. We also observed differences between temperate flies, however, with more reduction of expression plasticity in warm-temperate than in cold-temperate populations. Although in general, temperature-sensitive expression appeared to be detrimental in temperate climates, there were also cases in which plasticity was increased in temperate flies, as well as no changes in expression plasticity between flies from different climates.
Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Animais , Clima , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Feminino , Regulação da Expressão Gênica , Masculino , Proteínas do Grupo Polycomb , TemperaturaRESUMO
Current high-throughput experimental techniques make it feasible to infer gene regulatory interactions at the whole-genome level with reasonably good accuracy. Such experimentally inferred regulatory networks have become available for a number of simpler model organisms such as S. cerevisiae, and others. The availability of such networks provides an opportunity to compare gene regulatory processes at the whole genome level, and in particular, to assess similarity of regulatory interactions for homologous gene pairs either from the same or from different species. We present here a new technique for analyzing the regulatory interaction neighborhoods of paralogous gene pairs. Our central focus is the analysis of S. cerevisiae gene interaction graphs, which are of particular interest due to the ancestral whole-genome duplication (WGD) that allows to distinguish between paralogous transcription factors that are traceable to this duplication event and other paralogues. Similar analysis is also applied to E. coli and C. elegans networks. We compare paralogous gene pairs according to the presence and size of bi-fan arrays, classically associated in the literature with gene duplication, within other network motifs. We further extend this framework beyond transcription factor comparison to obtain topology-based similarity metrics based on the overlap of interaction neighborhoods applicable to most genes in a given organism. We observe that our network divergence metrics show considerably larger similarity between paralogues, especially those traceable to WGD. This is the case for both yeast and C. elegans, but not for E. coli regulatory network. While there is no obvious cross-species link between metrics, different classes of paralogues show notable differences in interaction overlap, with traceable duplications tending toward higher overlap compared to genes with shared protein families. Our findings indicate that divergence in paralogous interaction networks reflects a shared genetic origin, and that our approach may be useful for investigating structural similarity in the interaction networks of paralogous genes.
Assuntos
Caenorhabditis elegans/genética , Biologia Computacional/métodos , Escherichia coli/genética , Redes Reguladoras de Genes , Saccharomyces cerevisiae/genética , Animais , Evolução Molecular , Duplicação Gênica , Genoma , Fatores de Transcrição/genéticaRESUMO
Drosophila melanogaster recently spread from its tropical origin in Africa and became a cosmopolitan species that has adapted to a wide range of different thermal environments, including temperate climates. An important limiting factor of temperate climates has probably been their low and varying temperatures. The transcriptional output of genes can vary across temperatures, which might have been detrimental while settling in temperate environments. The reduction of temperature-sensitive expression of functionally important genes to ensure consistent levels of gene expression might have been relevant while adapting to such environments. In this study, we focus on the gene vestigial (vg) whose product is a key factor in wing development. We provide evidence that temperature-sensitivity of vg has been buffered in populations from temperate climates. We investigated temperature-sensitivity of vg gene expression in six natural populations, including four temperate populations (three from Europe and one from high-altitude Africa), and two tropical populations from the ancestral species range. All temperate populations exhibited a lower degree of temperature-induced expression plasticity than the tropical populations.
Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Proteínas Nucleares/genética , Temperatura , África , Animais , Europa (Continente) , Feminino , Expressão Gênica , MasculinoRESUMO
BACKGROUND: Despite continual progress in the identification and characterization of trait- and disease-associated variants that disrupt transcription factor (TF)-DNA binding, little is known about the distribution of TF binding deactivating mutations (deMs) in enhancer sequences. Here, we focus on elucidating the mechanism underlying the different densities of deMs in human enhancers. RESULTS: We identify two classes of enhancers based on the density of nucleotides prone to deMs. Firstly, fragile enhancers with abundant deM nucleotides are associated with the immune system and regular cellular maintenance. Secondly, stable enhancers with only a few deM nucleotides are associated with the development and regulation of TFs and are evolutionarily conserved. These two classes of enhancers feature different regulatory programs: the binding sites of pioneer TFs of FOX family are specifically enriched in stable enhancers, while tissue-specific TFs are enriched in fragile enhancers. Moreover, stable enhancers are more tolerant of deMs due to their dominant employment of homotypic TF binding site (TFBS) clusters, as opposed to the larger-extent usage of heterotypic TFBS clusters in fragile enhancers. Notably, the sequence environment and chromatin context of the cognate motif, other than the motif itself, contribute more to the susceptibility to deMs of TF binding. CONCLUSIONS: This dichotomy of enhancer activity is conserved across different tissues, has a specific footprint in epigenetic profiles, and argues for a bimodal evolution of gene regulatory programs in vertebrates. Specifically encoded stable enhancers are evolutionarily conserved and associated with development, while differently encoded fragile enhancers are associated with the adaptation of species.
Assuntos
Adaptação Biológica , Elementos Facilitadores Genéticos , Evolução Molecular , Mutação , Animais , Genes Reporter , Células Hep G2 , Humanos , Camundongos TransgênicosRESUMO
Gene expression levels are important quantitative traits that link genotypes to molecular functions and fitness. In Drosophila, population-genetic studies have revealed substantial adaptive evolution at the genomic level, but the evolutionary modes of gene expression remain controversial. Here, we present evidence that adaptation dominates the evolution of gene expression levels in flies. We show that 64% of the observed expression divergence across seven Drosophila species are adaptive changes driven by directional selection. Our results are derived from time-resolved data of gene expression divergence across a family of related species, using a probabilistic inference method for gene-specific selection. Adaptive gene expression is stronger in specific functional classes, including regulation, sensory perception, sexual behavior, and morphology. Moreover, we identify a large group of genes with sex-specific adaptation of expression, which predominantly occurs in males. Our analysis opens an avenue to map system-wide selection on molecular quantitative traits independently of their genetic basis.
Assuntos
Adaptação Fisiológica , Evolução Molecular , Animais , Drosophila/classificação , Drosophila/genética , Feminino , Masculino , Filogenia , Característica Quantitativa Herdável , Seleção Genética , Fatores SexuaisRESUMO
Understanding how gene regulation evolves is a key area in the current evolutionary field. Gene regulation occurs at various levels. Previous work on the evolution of gene regulation has largely focused on gene transcription. In this study, we used a recently developed ribosomal footprint profiling method to investigate how gene regulation evolves at both the transcription (mRNA abundance) and translation (ribosomal density) levels. By constructing a hybrid between Saccharomyces cerevisiae (Scer) and Saccharomyces bayanus (Sbay), which diverged â¼20 Ma, and quantifying transcriptome and translatome in both parental strains and their hybrid, we showed that translation is much more conserved than transcription, mostly due to the buffering effect of translational regulation for the transcriptional divergence. More conservation in translation than transcription is also confirmed by the inheritance mode of transcription and translation between two species. Furthermore, cis and trans effects are widely involved in changes at both transcription and translation levels. Finally, our results showed that genes with certain functions and sequence features might employ specific modes for evolution at these two critical levels of gene regulation. Our results demonstrated that it is essential to investigate the evolution of gene regulation at various levels from different genetic backgrounds to obtain a complete picture of its evolutionary modes in nature.
Assuntos
Evolução Molecular , Regulação da Expressão Gênica , Biossíntese de Proteínas , Transcrição Gênica , Padrões de Herança , Saccharomyces/genética , Saccharomyces cerevisiae/genéticaRESUMO
A major mode of gene expression evolution is based on changes in cis-regulatory elements (CREs) whose function critically depends on the presence of transcription factor-binding sites (TFBS). Because CREs experience extensive TFBS turnover even with conserved function, alignment-based studies of CRE sequence evolution are limited to very closely related species. Here, we propose an alternative approach based on a stochastic model of TFBS turnover. We implemented a maximum likelihood model that permits variable turnover rates in different parts of the species tree. This model can be used to detect changes in turnover rate as a proxy for differences in the selective pressures acting on TFBS in different clades. We applied this method to five TFBS in the fungi methionine biosynthesis pathway and three TFBS in the HoxA clusters of vertebrates. We find that the estimated turnover rate is generally high, with half-life ranging between approximately 5 and 150 My and a mode around tens of millions of years. This rate is consistent with the finding that even functionally conserved enhancers can show very low sequence similarity. We also detect statistically significant differences in the equilibrium densities of estrogen- and progesterone-response elements in the HoxA clusters between mammal and nonmammal vertebrates. Even more extreme clade-specific differences were found in the fungal data. We conclude that stochastic models of TFBS turnover enable the detection of shifts in the selective pressures acting on CREs in different organisms. The analysis tool, called CRETO (Cis-Regulatory Element Turn-Over) can be downloaded from http://www.bioinf.uni-leipzig.de/Software/creto/.