Floral Morphogenesis: Stochastic Explorations of a Gene Network Epigenetic Landscape

In contrast to the classical view of development as a preprogrammed and deterministic process, recent studies have demonstrated that stochastic perturbations of highly non-linear systems may underlie the emergence and stability of biological patterns. Herein, we address the question of whether noise contributes to the generation of the stereotypical temporal pattern in gene expression during flower development. We modeled the regulatory network of organ identity genes in the Arabidopsis thaliana flower as a stochastic system. This network has previously been shown to converge to ten fixed-point attractors, each with gene expression arrays that characterize inflorescence cells and primordial cells of sepals, petals, stamens, and carpels. The network used is binary, and the logical rules that govern its dynamics are grounded in experimental evidence. We introduced different levels of uncertainty in the updating rules of the network. Interestingly, for a level of noise of around 0.5–10%, the system exhibited a sequence of transitions among attractors that mimics the sequence of gene activation configurations observed in real flowers. We also implemented the gene regulatory network as a continuous system using the Glass model of differential equations, that can be considered as a first approximation of kinetic-reaction equations, but which are not necessarily equivalent to the Boolean model. Interestingly, the Glass dynamics recover a temporal sequence of attractors, that is qualitatively similar, although not identical, to that obtained using the Boolean model. Thus, time ordering in the emergence of cell-fate patterns is not an artifact of synchronous updating in the Boolean model. Therefore, our model provides a novel explanation for the emergence and robustness of the ubiquitous temporal pattern of floral organ specification. It also constitutes a new approach to understanding morphogenesis, providing predictions on the population dynamics of cells with different genetic configurations during development

Parallel evolution of amphioxus and vertebrate small-scale gene duplications

Background: Amphioxus are non-vertebrate chordates characterized by a slow morphological and molecular evolution. They share the basic chordate body-plan and genome organization with vertebrates but lack their 2R whole-genome duplications and their developmental complexity. For these reasons, amphioxus are frequently used as an outgroup to study vertebrate genome evolution and Evo-Devo. Aside from whole-genome duplications, genes continuously duplicate on a smaller scale. Smallscale duplicated genes can be found in both amphioxus and vertebrate genomes, while only the vertebrate genomes have duplicated genes product of their 2R wholegenome duplications. Here, we explore the history of small-scale gene duplications in the amphioxus lineage and compare it to small- and large-scale gene duplication history in vertebrates. Results: We present a study of the European amphioxus (Branchiostoma lanceolatum) gene duplications thanks to a new, high-quality genome reference. We fnd that, despite its overall slow molecular evolution, the amphioxus lineage has had a history of small-scale duplications similar to the one observed in vertebrates. We fnd parallel gene duplication profles between amphioxus and vertebrates and conserved func‑tional constraints in gene duplication. Moreover, amphioxus gene duplicates show lev‑ els of expression and patterns of functional specialization similar to the ones observed in vertebrate duplicated genes. We also fnd strong conservation of gene synteny between two distant amphioxus species, B. lanceolatum and B. foridae, with two major chromosomal rearrangements. Conclusions: In contrast to their slower molecular and morphological evolution, amphioxus' small-scale gene duplication history resembles that of the vertebrate line‑age both in quantitative and in functional terms

Patrones de marcaje visual en el oso pardo: un enfoque experimental

XV Congreso de la Sociedad Española para la Conservación y Estudio de los Mamíferos (SECEM), Córdoba, 4-7 diciembre de 2021.Peer reviewe

Genome-Wide Genotype-Expression Relationships Reveal Both Copy Number and Single Nucleotide Differentiation Contribute to Differential Gene Expression between Stickleback Ecotypes

Repeated and independent emergence of trait divergence that matches habitat differences is a sign of parallel evolution by natural selection. Yet, the molecular underpinnings that are targeted by adaptive evolution often remain elusive. We investigate this question by combining genome-wide analyses of copy number variants (CNVs), single nucleotide polymorphisms (SNPs), and gene expression across four pairs of lake and river populations of the three-spined stickleback (Gasterosteus aculeatus). We tested whether CNVs that span entire genes and SNPs occurring in putative cis-regulatory regions contribute to gene expression differences between sticklebacks from lake and river origins. We found 135 gene CNVs that showed a significant positive association between gene copy number and gene expression, suggesting that CNVs result in dosage effects that can fuel phenotypic variation and serve as substrates for habitat-specific selection. Copy number differentiation between lake and river sticklebacks also contributed to expression differences of two immune-related genes in immune tissues, cathepsin A and GIMAP7. In addition, we identified SNPs in cis-regulatory regions (eSNPs) associated with the expression of 1,865 genes, including one eSNP upstream of a carboxypeptidase gene where both the SNP alleles differentiated and the gene was differentially expressed between lake and river populations. Our study highlights two types of mutations as important sources of genetic variation involved in the evolution of gene expression and in potentially facilitating repeated adaptation to novel environments

Modeling and simulation of interlocus gene conversion

Les regions duplicades del genoma, com ara les duplicacions de segments (SDs), són una característica comuna dels genomes eucariotes i han estat associades a canvis fenotípics. Donada la seva rellevància evolutiva, tenir un model neutre per descriure la seva evolució és essencial. En aquesta tesi, descric el desenvolupament de SeDuS, un simulador computacional endavant en el temps de l'evolució neutra de SDs. Les duplicacions estan sotmeses a un procés de recombinació, anomenat conversió gènica interlocus (IGC), que afecta els patrons de variació i de desequilibri de lligament dins i entre duplicacions. Aquí descric els efectes de sobreposar regions susceptibles de recombinació homòloga amb regions susceptibles d'IGC i d'incorporar dependència d'IGC en la similitud de seqüències. Addicionalment, ja que les SDs són objectius potencial de la selecció natural, informo sobre possibles alteracions a proves estadístiques quan aquestes s'apliquen a regions duplicades sotmeses a IGC. Finalment, exploro la possibilitat de combinar resultats de diferents proves estadístiques aplicades al llarg de tot el genoma per detectar la presència de duplicacions col·lapsades.Duplicated regions of the genome, such as Segmental Duplications (SDs), are a pervasive feature of eukaryotic genomes and have been linked to phenotypic changes. Given their evolutionary relevance, having a neutral model to describe their evolution is essential. In this thesis, I report the development of SeDuS, a forward-in-time computer simulator of SD neutral evolution. Duplications are known to undergo a recombination process, termed interlocus gene conversion (IGC), which is known to affect the patterns of variation and linkage disequilibrium within and between duplicates. Here I describe the effects of overlapping crossover and IGC susceptible regions and of incorporating sequence similarity dependence of IGC. Furthermore, since SDs are potential targets of natural selection, I report potential confounding effects of IGC on test statistics when these are applied to duplications. Finally, I explore the possibility of combining results of different test statistics applied genome-wide to detect the presence of collapsed duplications

Collapsed duplications? What to expect amd what to look for

Trabajo presentado en la Annual Meeting of the Society for Molecular Biology and Evolution (SMBE 2015), celebrada en Viena del 12 al 16 de julio de 2015.Segmental duplications (SDs), defined as >1 kb regions of the genome with >90% similarity between copies, are an ubiquitous characteristic of eukaryotic genomes. Their evolution is known to be complex for several reasons: first, because SDs undergo interlocus gene conversion (IGC), a possible source of variation; second, reduced selective pressures may allow variants to increase in frequency more easily; and third, SDs are mediators of NAHR and formation of CNVs, which in turn are associated with susceptibility to disease. SD detection and characterization has been recognized as being of great importance. Ironically, most of the efforts dedicated to these tasks are aimed at eliminating SDs from genome-wide scans in order to avoid spurious signals coming from duplicated regions. Given that SDs are likely to be possible targets of natural selection, it would seem natural to look for SNPs under selection in duplications. However, to date there is no adequate test to detect selection in duplications precisely because none takes into account their complex evolution. Furthermore, the effect of applying neutrality tests to collapsed duplications is mostly ignored.N

Modeling and simulation of interlocus gene conversion

Les regions duplicades del genoma, com ara les duplicacions de segments (SDs), són una característica comuna dels genomes eucariotes i han estat associades a canvis fenotípics. Donada la seva rellevància evolutiva, tenir un model neutre per descriure la seva evolució és essencial. En aquesta tesi, descric el desenvolupament de SeDuS, un simulador computacional endavant en el temps de l'evolució neutra de SDs. Les duplicacions estan sotmeses a un procés de recombinació, anomenat conversió gènica interlocus (IGC), que afecta els patrons de variació i de desequilibri de lligament dins i entre duplicacions. Aquí descric els efectes de sobreposar regions susceptibles de recombinació homòloga amb regions susceptibles d'IGC i d'incorporar dependència d'IGC en la similitud de seqüències. Addicionalment, ja que les SDs són objectius potencial de la selecció natural, informo sobre possibles alteracions a proves estadístiques quan aquestes s'apliquen a regions duplicades sotmeses a IGC. Finalment, exploro la possibilitat de combinar resultats de diferents proves estadístiques aplicades al llarg de tot el genoma per detectar la presència de duplicacions col·lapsades.Duplicated regions of the genome, such as Segmental Duplications (SDs), are a pervasive feature of eukaryotic genomes and have been linked to phenotypic changes. Given their evolutionary relevance, having a neutral model to describe their evolution is essential. In this thesis, I report the development of SeDuS, a forward-in-time computer simulator of SD neutral evolution. Duplications are known to undergo a recombination process, termed interlocus gene conversion (IGC), which is known to affect the patterns of variation and linkage disequilibrium within and between duplicates. Here I describe the effects of overlapping crossover and IGC susceptible regions and of incorporating sequence similarity dependence of IGC. Furthermore, since SDs are potential targets of natural selection, I report potential confounding effects of IGC on test statistics when these are applied to duplications. Finally, I explore the possibility of combining results of different test statistics applied genome-wide to detect the presence of collapsed duplications