Genome sequence and analysis of the tuber crop potato

Potato (Solanum tuberosum L.) is the world's most important non-grain food crop and is central to global food security. It is clonally propagated, highly heterozygous, autotetraploid, and suffers acute inbreeding depression. Here we use a homozygous doubled-monoploid potato clone to sequence and assemble 86% of the 844-megabase genome. We predict 39,031 protein-coding genes and present evidence for at least two genome duplication events indicative of a palaeopolyploid origin. As the first genome sequence of an asterid, the potato genome reveals 2,642 genes specific to this large angiosperm clade. We also sequenced a heterozygous diploid clone and show that gene presence/absence variants and other potentially deleterious mutations occur frequently and are a likely cause of inbreeding depression. Gene family expansion, tissue-specific expression and recruitment of genes to new pathways contributed to the evolution of tuber development. The potato genome sequence provides a platform for genetic improvement of this vital crop.La lista completa de autores que integran el documento puede consultarse en el archivo.Facultad de Ciencias Exacta

Differential bicodon usage in lowly and highly abundant proteins

Degeneracy in the genetic code implies that different codons can encode the same amino acid. Usage preference of synonymous codons has been observed in all domains of life. There is much evidence suggesting that this bias has a major role on protein elongation rate, contributing to differential expression and to co-translational folding. In addition to codon usage bias, other preference variations have been observed such as codon pairs. In this paper, I report that codon pairs have significant different frequency usage for coding either lowly or highly abundant proteins. These usage preferences cannot be explained by the frequency usage of the single codons. The statistical analysis of coding sequences of nine organisms reveals that in many cases bicodon preferences are shared between related organisms. Furthermore, it is observed that misfolding in the drug-transport protein, encoded by MDR1 gene, is better explained by a big change in the pause propensity due to the synonymous bicodon variant, rather than by a relatively small change in codon usage. These findings suggest that codon pair usage can be a more powerful framework to understand translation elongation rate, protein folding efficiency, and to improve protocols to optimize heterologous gene expression.Universidad Nacional de La Plat

Genome sequence and analysis of the tuber crop potato

Potato (Solanum tuberosum L.) is the world's most important non-grain food crop and is central to global food security. It is clonally propagated, highly heterozygous, autotetraploid, and suffers acute inbreeding depression. Here we use a homozygous doubled-monoploid potato clone to sequence and assemble 86% of the 844-megabase genome. We predict 39,031 protein-coding genes and present evidence for at least two genome duplication events indicative of a palaeopolyploid origin. As the first genome sequence of an asterid, the potato genome reveals 2,642 genes specific to this large angiosperm clade. We also sequenced a heterozygous diploid clone and show that gene presence/absence variants and other potentially deleterious mutations occur frequently and are a likely cause of inbreeding depression. Gene family expansion, tissue-specific expression and recruitment of genes to new pathways contributed to the evolution of tuber development. The potato genome sequence provides a platform for genetic improvement of this vital crop.La lista completa de autores que integran el documento puede consultarse en el archivo.Facultad de Ciencias Exacta

Commentary: Systems Biology Approach to Model the Life Cycle of Trypanosoma cruzi

In a recent work we have identified, from a bigger gene regulatory network, a seven-node moduleinvolved in the control of the life cycle of Trypanosoma cruzi (T. cruzi) (Carrea and Diambra,2016). To that end, we have analyzed microarray gene-expression data of the four differentT. cruzi?s life cycle stages, by means of a systems biology approach. The found module is thesmallest gene regulatory subnetwork able to emulate the dynamical properties of the parasite.This module is composed of nine genes: three of them coding for uncharacterized proteins, andthe other six genes coding for characterized proteins. The latter code for: a hexokinase, a δ-1-pyrroline-5-carboxylate dehydrogenase, a quinone oxidoreductase, a glutamate dehydrogenase, apeptidyl-prolyl cis-trans isomerase, and a metaciclina II. Except for metaciclina II, these genes codefor proteins involved in metabolic pathways. Thus, we were expecting gene-expression regulatoryproteins instead of the striking information we obtained. Yet, it eventually became clear that thesemetabolic enzymes could have other regulatory functions beyond their known metabolic one. Thistype of multifunctional proteins are known as moonlighting proteins (Jeffery, 1999). They were firstdiscovered in the late 1980s by Piatigorsky et al. (1988). They found that the lens structural proteinδ-crystallin and the metabolic enzyme argininosuccinate lyase are both encoded by the same gene inducks. Today, it is well-known that moonlighting proteins comprise diverse kinds of proteins, andthat they are present in many different organisms including animals, plants, yeasts, prokaryotes,and protists (for reviews see Jeffery, 2009; Huberts and van der Klei, 2010; Jeffery, 2014).Fil: Carrea, Alejandra. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Diambra, Luis Anibal. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Systems biology approach to model the life cycle of Trypanosoma cruzi

Due to recent advances in reprogramming cell phenotypes, many efforts have been dedicated to developing reverse engineering procedures for the identification of gene regulatory networks that emulate dynamical properties associated with the cell fates of a given biological system. In this work, we propose a systems biology approach for the reconstruction of the gene regulatory network underlying the dynamics of the Trypanosoma cruzi's life cycle. By means of an optimisation procedure, we embedded the steady state maintenance, and the known phenotypic transitions between these steady states in response to environmental cues, into the dynamics of a gene network model. In the resulting network architecture we identified a small subnetwork, formed by seven interconnected nodes, that controls the parasite's life cycle. The present approach could be useful for better understanding other single cell organisms with multiple developmental stages.Revisión disponible en http://sedici.unlp.edu.ar/handle/10915/87345Centro Regional de Estudios Genómico

COVID-19 Mortality and the Cytokine Storm: An Added Value for APOE Genotyping

The new COVID-19 presents some comorbidities, such as obesity, Alzheimer’s, and coronary risk, among others. We argue that the current understanding of some of these clinical conditions may illuminate the design of future COVID-19 studies to account for a bias that may be the cause of the para-doxical associations between COVID-19 mortality and cytokine storm. Given that we know some of the genetic mechanisms behind these diseases, it is possible to circumscribe these studies to some key genes that help us understand why some patients experience a cytokine storm and what the treatment strategies might be. In this paper, we discuss the role of A2M and APOE genes. A2M encodes a multifaceted protein which is highly expressed in the liver and released to the bloodstream associated with the apolipopro-tein E. This association depends on the APOE genotype. A2M has protease-clearing activity binding of a broad range of proteases, such as thrombin and Factor Xa. It also presents the ability to bind to proin-flammatory ligands, like cytokines. Further, A2M acts as chaperone of misfolded substrates, like beta-amyloid peptide. The last two molecular functions grant it a key role in regulating both inflammatory processes, as well as extracellular protein homeostasis. For these reasons, we conclude that A2M-APOE association will have prophylactic, therapeutic, and prognostic implications; and the proper understanding of the physiological role of APOE and A2M in controlling inflammatory processes can shed further light on the putative treatment of COVID-19-derived cytokine storm.Fil: Diambra, Luis Anibal. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Rastmanesh, Reza. No especifíca

Editorial: Emergent Effects of Noise in Biology: From Gene Expression to Cell Motility

Deterministic modeling coarse-grains unitary events into population behavior, however this approach often misses the diversity of responses in cellular and molecular systems, due to long-time effects of stochastic fluctuations. The origins of stochasticity in biological systems are multiple and it is now generally accepted that this stochasticity can play key roles in emergent biological function at many scales: from intracellular processes to populations of macroscopic individuals. One can distinguish two sources: intrinsic fluctuations related to molecular processes, as those involved in biochemical reactions (in many instances the count of molecules participating in these processes is low, and so their stochastic nature becomes apparent); and extrinsic fluctuations due to random changes in the environment surrounding affecting the time evolution of the system.Fil: Diambra, Luis Anibal. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Santillán, Moisés. Centro de Investigacion y Estudios Avanzados del Ipn.; Méxic

Modeling the emergence of circadian rhythms in a clock neuron network

Circadian rhythms in pacemaker cells persist for weeks in constant darkness, while in other types of cells the molecular oscillations that underlie circadian rhythms damp rapidly under the same conditions. Although much progress has been made in understanding the biochemical and cellular basis of circadian rhythms, the mechanisms leading to damped or self-sustained oscillations remain largely unknown. There exist many mathematical models that reproduce the circadian rhythms in the case of a single cell of the Drosophila fly. However, not much is known about the mechanisms leading to coherent circadian oscillation in clock neuron networks. In this work we have implemented a model for a network of interacting clock neurons to describe the emergence (or damping) of circadian rhythms in Drosophila fly, in the absence of zeitgebers. Our model consists of an array of pacemakers that interact through the modulation of some parameters by a network feedback. The individual pacemakers are described by a well-known biochemical model for circadian oscillation, to which we have added degradation of PER protein by light and multiplicative noise. The network feedback is the PER protein level averaged over the whole network. In particular, we have investigated the effect of modulation of the parameters associated with (i) the control of net entrance of PER into the nucleus and (ii) the non-photic degradation of PER. Our results indicate that the modulation of PER entrance into the nucleus allows the synchronization of clock neurons, leading to coherent circadian oscillations under constant dark condition. On the other hand, the modulation of non-photic degradation cannot reset the phases of individual clocks subjected to intrinsic biochemical noise.Facultad de Ciencias Exacta

SARS-CoV-2 Codon Usage Bias Downregulates Host Expressed Genes With Similar Codon Usage

Severe acute respiratory syndrome has spread quickly throughout the world and was declared a pandemic by the World Health Organization (WHO). The pathogenic agent is a new coronavirus (SARS-CoV-2) that infects pulmonary cells with great effectiveness. In this study we focus on the codon composition for the viral protein synthesis and its relationship with the protein synthesis of the host. Our analysis reveals that SARS-CoV-2 preferred codons have poor representation of G or C nucleotides in the third position, a characteristic which could result in an unbalance in the tRNAs pools of the infected cells with serious implications in host protein synthesis. By integrating this observation with proteomic data from infected cells, we observe a reduced translation rate of host proteins associated with highly expressed genes and that they share the codon usage bias of the virus. The functional analysis of these genes suggests that this mechanism of epistasis can contribute to understanding how this virus evades the immune response and the etiology of some deleterious collateral effect as a result of the viral replication. In this manner, our finding contributes to the understanding of the SARS-CoV-2 pathogeny and could be useful for the design of a vaccine based on the live attenuated strategy.Fil: Alonso, Andrés Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Diambra, Luis Anibal. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin