Nicolas Frankel

University of Buenos Aires | UBA · IFIByNE

Understanding the evolutionary potential of mutations in gene regulatory networks is essential to furthering the study of evolution and development. However, in multicellular systems, genetic manipulation of regulatory networks in a targeted and high-throughput way remains challenging. In this study, we designed TF-High-Evolutionary (HighEvo), a tr...

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 ecologica...

Evolutionary analyses have estimated that ∼60% of nucleotides in intergenic regions of the Drosophila melanogaster genome are functionally relevant, suggesting that regulatory information may be encoded more densely in intergenic regions than has been revealed by most functional dissections of regulatory DNA. Here, we approached this issue through...

Animal genomes are compartmentalized into insulated regulatory units named topology-associated domains (TADs). TADs insulate gene promoters from enhancers that occupy neighboring TADs. Chromosomal rearrangements that disrupt TAD structure can generate new regulatory interactions between enhancers and promoters that were once separated into differen...

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 form a tractable system to study the transition from chemically simpler breeding sites (like prickly pears of the ge...

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. Historically, enhancers have been regarded as highly tissue-specific. However, recent evidence has demonstrated that many enhancers are pleiotrop...

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 Opu...

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...

The cuticle of insects is decorated with non-sensory hairs called trichomes. A few Drosophila species independently lost most of the dorso-lateral trichomes on first instar larvae. Genetic experiments revealed that this naked cuticle phenotype was caused by the evolution of enhancer function at the ovo/shavenbaby (ovo/svb) locus. Here we explore ho...

Las cuencas urbanas son sistemas socio-ecológicos-tecnológicos cuyos componentes interaccionan con las comunidades bacterianas de los ecosistemas acuáticos. Con objeto de distinguir los efectos de infraestructuras urbanas y del micro-hábitat ecológico sobre la estructura del bacterioplancton, se establecieron 14 sitios de muestreo sobre una red hid...

Escherichia coli dynamics in urban watersheds are affected by a complex balance among external inputs, niche modulation and genetic variability. To explore the ecological processes influencing E. coli spatial patterns, we analyzed its abundance and phylogenetic structure in water samples from a stream network with heterogeneous urban infrastructure...

La presencia de patógenos en aguas superficiales es una problemática ambiental y sanitaria, siendo las enfermedades de transmisión por agua una de las principales causales de morbilidad en países en desarrollo. Complementariamente, las cuencas urbanas integran factores socio-ecológico-tecnológicos que interaccionan con la comunidad microbiana. Con...

Escherichia coli dynamics in urban watersheds are affected by a complex balance among external inputs, niche modulation and genetic variability. To explore the ecological processes influencing E. coli spatial patterns, we analyzed its abundance and phylogenetic structure in water samples from a stream network with heterogeneous urban infrastructure...

Despite considerable progress in recent decades in dissecting the genetic causes of natural morphological variation, there is limited understanding of how variation within species ultimately contributes to species differences. We have studied patterning of the non‐sensory hairs, commonly known as “trichomes,” on the dorsal cuticle of first‐instar l...

E. coli persistence in urban watersheds is a challenge to microbial pollution management and a matter of sanitary concern. To explore the ecological processes influencing the spatial patterns of E. coli, we analyzed its abundance and intraspecific phylogenetic structure in water samples of a stream network with heterogeneous infrastructure and envi...

Presentación de la estructura filogenética de Escherichia coli hallada en la cuenca de los arroyos Las Piedras, San Francisco y Santo Domingo (febrero 2018), y del análisis de su varianza en función de métricas urbanas y ambientales, a la vez que de factores espaciales mediante el uso de AEMs específicos para sistemas lóticos.

The current paradigm in the field of gene regulation postulates that regulatory information for generating gene expression is organized into modules (enhancers), each containing the information for driving gene expression in a single spatiotemporal context. This modular organization is thought to facilitate the evolution of gene expression by minim...

La persistencia de Escherichia coli en ambientes secundarios a su hábitat natural es de fundamental importancia sanitaria y ecológica, en particular en los centros urbanos donde su ocurrencia es ubicua. Nuestro objetivo fue evaluar el efecto de distintos condicionantes urbanos sobre la abundancia y diversidad genética de E. coli. El área de estudio...

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, th...

Expression of miR-92a and sha-ΔUTR under control of different VT GAL4 drivers. (A, A’, B, B’) Trichomes on the wing are largely repressed upon expression of miR-92a under control of VT057077. Note that trichomes on the alula (arrowhead in B) develop normally. Also trichomes on T1 and T3 legs (C, C’ D, F, F’, G) and on the halteres (E, E’, H, H’) ar...

GFP expression driven by tallacZGAL4. GFP is expressed throughout all the leg segments (A) including the femur (B) of the second leg. Mutant clones of tals18 (C) (brown shaded area) and svbR9 (D) (red shaded area) lack trichomes on the femur of a second leg. (JPG)

Comparison of RNA expression levels of upstream trichome network genes for T2 legs at 24 hAPF from two strains with different naked valley size (e4, wo1, ro1 (eworo, large naked valley) and OregonR (OreR, small naked valley)). Genes are sorted by gene name. Two rows for a gene indicate alternative transcription start sites. Expression level in frag...

Comparison of RNA expression levels of genes downstream of svb [29,33] for T2 legs at 24 hAPF from two strains with different naked valley size [e4, wo1, ro1 (eworo, large naked valley) and OregonR (OreR, small naked valley)]. Genes are sorted by gene name. Two rows for a gene indicate alternative transcription start sites. Expression level in frag...

GFP expression driven by svbBAC-GFP. GFP is expressed throughout the posterior femur of a T2 leg at 24 hAPF. (JPG)

Analysis of trichome length after knockdown of CG14395. Expression of the RNAi construct and UAS-Dicer was under control of GAL4 driver lines VT042733 (drives in the proximal femur) and VT057077 (drives in the whole leg). Box plots show the length of trichomes in the distal part of the posterior femur and around the naked valley (NV). Parents (UAS-...

Comparison of RNA expression levels of genes independent of svb [33,36] for T2 legs at 24 hAPF from two strains with different naked valley size [e4, wo1, ro1 (eworo, large naked valley) and OregonR (OreR, small naked valley)]. Genes are sorted by gene name. Two rows for a gene indicate alternative transcription start sites. Expression level in fra...

Trichomes gained ectopically in the naked valley have different morphologies. (A) Trichomes gained in the naked valley after loss of miR-92a and miR-92b have a similar morphology as trichomes on the more distal femur. Trichomes gained after ectopic expression of sha-ΔUTR (B) are significantly shorter, while trichomes developing after expression of...

Naked valley size in deficiency line Df(X)106 and control line f02952,f06356. The control line still contains both pBac insertions used to generate the deficiency [5,43]. There is no detectable difference in naked valley size or trichome density between deficiency and control flies at 25°C, 29°C, or 17°C. (JPG)

Expression of GFP under control of different VDRC GAL4 drivers in pupae at 22–26 hAPF. All tested drivers show some expression in T2 legs as well as in other pupal tissues. (JPG)

FPKM values (with high and low confidence values) after transcript quantification with cufflinks for Oregon R replicate 1. (CSV)

FPKM values (with high and low confidence values) after transcript quantification with cufflinks for e,wo,ro replicate 1. (CSV)

FPKM values (with high and low confidence values) for both Oregon R and e,wo,ro after comparison with cuffdiff. (CSV)

Oregon R svb locus ATAC-seq peaks (called with MACS2) with information about position, summit position, height, -log10 (p and q values), and enrichment. (TXT)

FPKM values (with high and low confidence values) after transcript quantification with cufflinks for Oregon R replicate 3. (CSV)

FPKM values (with high and low confidence values) after transcript quantification with cufflinks for Oregon R replicate 2. (CSV)

FPKM values (with high and low confidence values) after transcript quantification with cufflinks for e,wo,ro replicate 3. (CSV)

FPKM values (with high and low confidence values) after transcript quantification with cufflinks for e,wo,ro replicate 2. (CSV)

e,wo,ro svb locus ATAC-seq peaks (called with MACS2) with information about position, summit position, height, -log10 (p and q values), and enrichment. (TXT)

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, th...

Developmental genes can have complex cis-regulatory regions with multiple enhancers. Early work revealed remarkable modularity of enhancers, whereby distinct DNA regions drive gene expression in defined spatiotemporal domains. Nevertheless, a few reports have shown that enhancers function in multiple developmental stages, implying that enhancers ca...

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...

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 genet...

Novel body structures are often generated by the redeployment of ancestral components of the genome. In this issue of Developmental Cell, Glassford et al. (2015) present a thorough analysis of the co-option of a gene regulatory network in the origin of an evolutionary novelty.

The stochastic nature of biochemical processes is a source of variability that influences developmental stability. Developmental instability (DI) is often estimated through fluctuating asymmetry (FA), a parameter that deals with within-individual variation in bilateral structures. A relevant goal is to shed light on how environment, physiology and...

In animals, Hox transcription factors define regional identity in distinct anatomical domains. How Hox genes encode this specificity is a paradox, because different Hox proteins bind with high affinity in vitro to similar DNA sequences. Here, we demonstrate that the Hox protein Ultrabithorax (Ubx) in complex with its cofactor Extradenticle (Exd) bo...

In this paper, we provide a historical account of the contribution of a single line of research to our current understanding of the structure of cis-regulatory regions and the genetic basis for morphological evolution. We revisit the experiments that shed light on the evolution of larval cuticular patterns within the genus Drosophila and the evolut...

Even though there is no universal criterion for species definition, the key event in speciation research is the advent of reproductive isolation or barriers that prevent gene flow between populations. The search for genetic factors underlying isolating barriers is the field of speciation genetics. The development of sophisticated methods of genetic...

Phenotypic characters that display continuous variation are usually called ‘quantitative traits’ or ‘complex traits’. Alternatively, geneticists refer to them as ‘multigene traits’, because the underlying genetic architecture is assumed to be polygenic. Analyses of the genetic architecture of diverse quantitative traits suggest that the number of l...

Asr (for ABA, stress, ripening) genes are exclusively found in the genomes of higher plants and the encoded proteins have been found localized both to the nucleus and cytoplasm. However, before the mechanisms underlying the activity of ASR proteins can be determined, the role of these proteins in planta should be deciphered. Results from the presen...

Genomes contain the necessary information to ensure that genes are expressed in the right place, at the right time, and with the proper rate. Metazoan developmental genes often possess long stretches of DNA flanking their coding sequences and/or large introns which contain elements that influence gene expression. Most of these regulatory elements a...

Similar morphological, physiological, and behavioral features have evolved independently in different species, a pattern known as convergence. It is known that morphological convergence can occur through changes in orthologous genes. In some cases of convergence, cis-regulatory changes generate parallel modifications in the expression patterns of o...

Morphology evolves often through changes in developmental genes, but the causal mutations, and their effects, remain largely unknown. The evolution of naked cuticle on larvae of Drosophila sechellia resulted from changes in five transcriptional enhancers of shavenbaby (svb), a transcript of the ovo locus that encodes a transcription factor that gov...

Genes include cis-regulatory regions that contain transcriptional enhancers. Recent reports have shown that developmental genes often possess multiple discrete enhancer modules that drive transcription in similar spatio-temporal patterns: primary enhancers located near the basal promoter and secondary, or 'shadow', enhancers located at more remote...

The Asr gene family (named after abscicic acid [ABA], stress, ripening), exclusively present in plant genomes, is involved in transcriptional regulation. Its members are up-regulated in roots and leaves of water- or salt-stressed plants. In previous work, evidence of adaptive evolution (as inferred from synonymous and nonsynonymous divergence rates...

Asr genes are exclusively found in the genomes of higher plants. In many species, this gene family is expressed under abiotic stress conditions and during fruit ripening. The encoded proteins have nuclear localisation and consequently a transcription factor function has been suggested. Interestingly, yeast-one-hybrid experiments revealed that a gra...