Biology subjects

Frankel, N.

Publications and source records attributed to Frankel, N..

8 recordsLinked to original sources

bioRxiv2025

Distinct mechanisms decommission redundant enhancers to facilitate phenotypic evolution

The evolutionary loss of morphological traits is often driven by changes in gene regulation. Many developmental genes are controlled by multiple, redundant enhancers, raising the question of how robust regulatory systems can be dismantled to permit phenotypic transitions. We show that the loss of larval trichomes in Drosophila sechellia resulted from the independent inactivation of four embryonic enhancers of the shavenbaby gene. Each enhancer was extinguished by a distinct mechanism: (1) a large deletion that removed essential sequences, (2) the loss of activator sites and gain of repressor sites, (3) the acquisition of a long-range silencer, and (4) the unmasking of pre-existing repression. Notably, three of these mechanisms relied on repression, pointing to repression as a rapid route for the evolutionary loss of robust regulatory elements. These results show that robustness in gene regulation does not prevent morphological change but instead provides multiple opportunities for mutations to reduce enhancer activity, giving selection many paths to reshape form.

evolutionary biology↗

bioRxiv2024

Ecotype-specific genomic features within the Escherichia cryptic clade IV

Escherichia cryptic clades represent a relatively unexplored taxonomic cluster believed to exhibit characteristics associated with a free-living lifestyle, which is known as the environmental hypothesis. This hypothesis suggests that certain Escherichia strains harbour traits that favour their environmental persistence, thus expanding the ecological commensal niche of the genus. While surveying Escherichia diversity in an urban South American stream we isolated the first environmental cryptic clade IV strain in South America (339_SF). Here we report the genomic characterization of 339_SF strain in the context of existing genomic information for cryptic clade IV. A comparative analysis of genomes within the same clade stemming from diverse ecological sources and geographical locations reveals close phylogenetic proximity between our isolate and strains of environmental origin. In the genomes of cryptic clade IV strains that were isolated from environmental niches we observed enrichment of functional genes related to responses to adverse environmental conditions and a low number of genes with clinical relevance among. Our findings highlight substantial intra-group genomic structuring linked to ecological origin and shed light on the genomic mechanisms underlying the naturalization phenomena within the Escherichia genus.

microbiology↗

bioRxiv2023

The density of regulatory information is a major determinant of evolutionary constraint on non-coding DNA in Drosophila

The density and distribution of regulatory information in non-coding DNA of eukaryotic genomes is largely unknown. Evolutionary analyses have estimated that [~]60% of nucleotides in intergenic regions of the D. melanogaster genome is functionally relevant. This estimate is difficult to reconcile with the commonly accepted idea that enhancers are compact regulatory elements that generally encompass less than 1 kilobase of DNA. Here, we approached this issue through a functional dissection of the regulatory region of the gene shavenbaby (svb). Most of the [~]90 kilobases of this large regulatory region is highly conserved in the genus Drosophila, though characterized enhancers occupy a small fraction of this region. By analyzing the regulation of svb in different contexts of Drosophila development, we found that the regulatory architecture that drives svb expression in the abdominal pupal epidermis is organized in a dramatically different way than the information that drives svb expression in the embryonic epidermis. While in the embryonic epidermis svb is activated by compact and dispersed enhancers, svb expression in the pupal epidermis is driven by large regions with enhancer activity, which occupy a great portion of the svb cis-regulatory DNA. We observed that other developmental genes also display a dense distribution of putative regulatory elements in their regulatory regions. Furthermore, we found that a large percentage of conserved non-coding DNA of the Drosophila genome is contained within putative regulatory DNA. These results suggest that part of the evolutionary constraint on non-coding DNA of Drosophila is explained by the density of regulatory information.

genetics↗

bioRxiv2022

Phylogenomics provides insights into the evolution of cactophily and host plant shifts in Drosophila

Cactophilic species of the Drosophila buzzatii cluster (repleta group) comprise an excellent model group to investigate genomic changes underlying adaptation to extreme climate conditions and host plants. In particular, these species offer a subject to study the transition from chemically simpler breeding sites (like prickly pears of the genus Opuntia) to chemically more complex hosts (columnar cacti). Here, we report four highly contiguous genome assemblies of three species of the buzzatii cluster. Based on this genomic data and inferred phylogenetic relationships, we identified candidate taxonomically restricted genes (TRGs) likely involved in the evolution of cactophily and cactus host specialization in internal branches of the subgenus Drosophila. Functional enrichment analyses of TRGs within the buzzatii cluster identified genes involved in detoxification, water preservation, immune system response, anatomical structure development, and morphogenesis. In contrast, processes that regulate responses to stress, as well as the metabolism of nitrogen compounds, transport, and secretion were found in the set of species that are columnar cacti dwellers. These findings are in line with the hypothesis that those genomic innovations brought about instrumental mechanisms underlying adaptation in a group of species that speciated in the arid regions of South America.

evolutionary biology↗

bioRxiv2022

Pleiotropic enhancers are ubiquitous regulatory elements in the human genome

Enhancers are regulatory elements of genomes that determine spatio-temporal patterns of gene expression. The human genome contains a vast number of enhancers, which largely outnumber protein-coding genes. Classically, enhancers have been regarded as highly tissue-specific. However, recent evidence suggests that many enhancers are pleiotropic, with activity in multiple developmental contexts. Yet, the extent and impact of pleiotropy remain largely unexplored. In this study we predicted active enhancers across human organs based on the analysis of both eRNA transcription (FANTOM5 consortium datasets) and chromatin architecture (ENCODE consortium datasets). We show that pleiotropic enhancers are pervasive in the human genome and that most enhancers active in a particular organ are also active in other organs. In addition, our analysis suggests that the proportion of context-specific enhancers of a given organ is explained, at least in part, by the proportion of context-specific genes in that same organ. The notion that such a high proportion of human enhancers can be pleiotropic suggests that small regions of regulatory DNA contain abundant regulatory information and that these regions evolve under important evolutionary constraints. Significance statementThe human genome contains a vast number of regulatory elements, named enhancers, that control the tempo and mode of gene expression. Classically, enhancers have been regarded as genetic elements that are active in a single organ, but recent evidence suggests that many enhancers in animal genomes are active in multiple organs (i.e., are pleiotropic). Here we shed light on the architecture of non-coding human DNA by showing that a large percentage of the enhancers of the human genome are pleiotropic and that the majority of enhancers active in a particular organ are pleiotropic. This suggests that small regions of regulatory DNA may contain abundant regulatory information and that these regions evolve under important evolutionary constraints.

genomics↗

bioRxiv2017

Gene regulatory network architecture in different developmental contexts influences the genetic basis of morphological evolution

Convergent phenotypic evolution is often caused by recurrent changes at particular nodes in the underlying gene regulatory networks (GRNs). The genes at such evolutionary hotspots are thought to maximally affect the phenotype with minimal pleiotropic consequences. This has led to the suggestion that if a GRN is understood in sufficient detail, the path of evolution may be predictable. The repeated evolutionary loss of larval trichomes among Drosophila species is caused by the loss of shavenbaby (svb) expression. svb is also required for development of leg trichomes, but the evolutionary gain of trichomes in the naked valley on T2 femurs in Drosophila melanogaster is caused by the loss of microRNA-92a (miR-92a) expression rather than changes in svb. We compared the expression and function of components between the larval and leg trichome GRNs to investigate why the genetic basis of trichome pattern evolution differs in these developmental contexts. We found key differences between the two networks in both the genes employed, and in the regulation and function of common genes. These differences in the GRNs reveal why mutations in svb are unlikely to contribute to leg trichome evolution and how instead miR-92a represents the key evolutionary switch in this context. Our work shows that variability in GRNs across different developmental contexts, as well as whether a morphological feature is lost versus gained, influence the nodes at which a GRN evolves to cause morphological change. Therefore, our findings have important implications for understanding the pathways and predictability of evolution.\n\nAuthor SummaryA major goal of biology is to identify the genetic cause of organismal diversity. Convergent evolution of traits is often caused by changes in the same genes - evolutionary hotspots. shavenbaby is a hotspot for larval trichome loss in Drosophila, however microRNA-92a underlies the gain of leg trichomes. To understand this difference in the genetics of phenotypic evolution, we compared the expression and function of genes in the underlying regulatory networks. We found that the pathway of evolution is influenced by differences in gene regulatory network architecture in different developmental contexts, as well as by whether a trait is lost or gained. Therefore, hotspots in one context may not readily evolve in a different context. This has important implications for understanding the genetic basis of phenotypic change and the predictability of evolution.

evolutionary biology↗

bioRxiv2017

Pleiotropy in enhancer function is encoded through diverse genetic architectures

Developmental genes can have complex c/s-regulatory regions, with multiple enhancers scattered across stretches of DNA spanning tens or hundreds of kilobases. Early work revealed remarkable modularity of enhancers, where distinct regions of DNA, bound by combinations of transcription factors, drive gene expression in defined spatio-temporal domains. Nevertheless, a few reports have shown that enhancer function may be required in multiple developmental stages, implying that regulatory elements can be pleiotropic. In these cases, it is not clear whether the pleiotropic enhancers employ the same transcription factor binding sites to drive expression at multiple developmental stages or whether enhancers function as chromatin scaffolds, where independent sets of transcription factor binding sites act at different stages. In this work we have studied the activity of the enhancers of the shavenbaby gene throughout D. melanogaster development. We found that all seven shavenbaby enhancers drive gene expression in multiple tissues and developmental stages at varying levels of redundancy. We have explored how this pleiotropy is encoded in two of these enhancers. In one enhancer, the same transcription factor binding sites contribute to embryonic and pupal expression, whereas for a second enhancer, these roles are largely encoded by distinct transcription factor binding sites. Our data suggest that enhancer pleiotropy might be a common feature of c/s-regulatory regions of developmental genes and that this pleiotropy can be encoded through multiple genetic architectures.

genetics↗

bioRxiv2016

Genetic and transgenic reagents for Drosophila simulans, D.mauritiana, D. yakuba, D. santomea and D. virilis

Species of the Drosophila melanogaster species subgroup, including the species D. simulans, D. mauritiana, D. yakuba, and D. santomea, have long served as model systems for studying evolution. Studies in these species have been limited, however, by a paucity of genetic and transgenic reagents. Here we describe a collection of transgenic and genetic strains generated to facilitate genetic studies within and between these species. We have generated many strains of each species containing mapped piggyBac transposons including an enhanced yellow fluorescent protein gene expressed in the eyes and a phiC31 attP site-specific integration site. We have tested a subset of these lines for integration efficiency and reporter gene expression levels. We have also generated a smaller collection of other lines expressing other genetically encoded fluorescent molecules in the eyes and a number of other transgenic reagents that will be useful for functional studies in these species. In addition, we have mapped the insertion locations of 58 transposable elements in D. virilis that will be useful for genetic mapping studies.

genetics↗