Computational analysis of the evolutionarily conserved Missing In Metastasis/Metastasis Suppressor 1 gene predicts novel interactions, regulatory regions and transcriptional control

Missing in Metastasis (MIM), or Metastasis Suppressor 1 (MTSS1), is a highly conserved protein, which links the plasma membrane to the actin cytoskeleton. MIM has been implicated in various cancers, however, its modes of action remain largely enigmatic. Here, we performed an extensive in silico characterisation of MIM to gain better understanding of its function. We detected previously unappreciated functional motifs including adaptor protein (AP) complex interaction site and a C-helix, pointing to a role in endocytosis and regulation of actin dynamics, respectively. We also identified new functional regions, characterised with phosphorylation sites or distinct hydrophilic properties. Strong negative selection during evolution, yielding high conservation of MIM, has been combined with positive selection at key sites. Interestingly, our analysis of intra-molecular co-evolution revealed potential regulatory hotspots that coincided with reduced potentially\ua0pathogenic polymorphisms. We explored databases for the mutations and expression levels of MIM in cancer. Experimentally, we focused on chronic lymphocytic leukaemia (CLL), where MIM showed high overall expression, however, downregulation on poor prognosis samples. Finally, we propose strong conservation of MTSS1 also on the transcriptional level and predict novel transcriptional regulators. Our data highlight important targets for future studies on the role of MIM in different tissues and cancers

Introducing evolutionary biologists to the analysis of big data: guidelines to organize extended bioinformatics training courses

Research in evolutionary biology has been progressively influenced by big data such as massive genome and transcriptome sequencing data, scalar measurements of several phenotypes on tens to thousands of individuals, as well as from collecting worldwide environmental data at an increasingly detailed scale. The handling and analysis of such data require computational skills that usually exceed the abilities of most traditionally trained evolutionary biologists. Here we discuss the advantages, challenges and considerations for organizing and running bioinformatics training courses of 2–3 weeks in length to introduce evolutionary biologists to the computational analysis of big data. Extended courses have the advantage of offering trainees the opportunity to learn a more comprehensive set of complementary topics and skills and allowing for more time to practice newly acquired competences. Many organizational aspects are common to any course, as the need to define precise learning objectives and the selection of appropriate and highly motivated instructors and trainees, among others. However, other features assume particular importance in extended bioinformatics training courses. To successfully implement a learning-by-doing philosophy, sufficient and enthusiastic teaching assistants (TAs) are necessary to offer prompt help to trainees. Further, a good balance between theoretical background and practice time needs to be provided and assured that the schedule includes enough flexibility for extra review sessions or further discussions if desired. A final project enables trainees to apply their newly learned skills to real data or case studies of their interest. To promote a friendly atmosphere throughout the course and to build a close-knit community after the course, allow time for some scientific discussions and social activities. In addition, to not exhaust trainees and TAs, some leisure time needs to be organized. Finally, all organization should be done while keeping the budget within fair limits. In order to create a sustainable course that constantly improves and adapts to the trainees’ needs, gathering short- and long-term feedback after the end of the course is important. Based on our experience we have collected a set of recommendations to effectively organize and run extended bioinformatics training courses for evolutionary biologists, which we here want to share with the community. They offer a complementary way for the practical teaching of modern evolutionary biology and reaching out to the biological community.Peer reviewe

Inferring the evolution of the major histocompatibility complex of wild pigs and peccaries using hybridisation DNA capture-based sequencing

The major histocompatibility complex (MHC) is a key genomic model region for understanding the evolution of gene families and the co-evolution between host and pathogen. To date, MHC studies have mostly focused on species from major vertebrate lineages. The evolution of MHC classical (Ia) and non-classical (Ib) genes in pigs has attracted interest because of their antigen presentation roles as part of the adaptive immune system. The pig family Suidae comprises over 18 extant species (mostly wild), but only the domestic pig has been extensively sequenced and annotated. To address this, we used a DNA-capture approach, with probes designed from the domestic pig genome, to generate MHC data for 11 wild species of pigs and their closest living family, Tayassuidae. The approach showed good efficiency for wild pigs (~80% reads mapped, ~87× coverage), compared to tayassuids (~12% reads mapped, ~4× coverage). We retrieved 145 MHC loci across both families. Phylogenetic analyses show that the class Ia and Ib genes underwent multiple duplications and diversifications before suids and tayassuids diverged from their common ancestor. The histocompatibility genes mostly form orthologous groups and there is genetic differentiation for most of these genes between Eurasian and sub-Saharan African wild pigs. Tests of selection showed that the peptide-binding region of class Ib genes was under positive selection. These findings contribute to better understanding of the evolutionary history of the MHC, specifically, the class I genes, and provide useful data for investigating the immune response of wild populations against pathogens

Memorias : XX Congreso Institucional de Investigaciones

Este documento, recoge 10 resúmenes de los trabajos presentados como resultado del proyecto en investigación sobre salud oral e investigación en ingeniería, salud y medio ambiente y biología, para el XX congreso institucional de investigaciones de la Universidad del Bosque. Los productos obtenidos como parte de la investigación son: (1) Condición periodontal en pacientes colombianos con artritis idiopática juvenil (AIJ); (2) Efecto del ácido hipocloroso sobre el sistema amortiguador del pH de la saliva. Estudio in vitro e in vivo; (3) Efecto oxidativo del ácido hipocloroso sobre las proteínas salivales: estudio in vitro; (4) Evaluación del ácido hipocloroso como agente antiplaca para uso en la cavidad oral. Parte I: sustantividad, efecto antiplaca y efectos adversos; (5) Identificación de los factores de virulencia de Klebsiella pneumoniae aislada de cavidad oral asociada a fuentes de contaminación exógena; (6) Modulación de la expresión de factores de crecimiento por ácido hipocloroso sobre fibroblastos gingivales humanos; (7) Potencial de diferenciación y expansión neuronal in vitro a partir de Células Troncales de pulpa dental humana; (8) Resolvina D1 inhibe la expresión de moléculas de adhesión en células endoteliales de arteria coronaria humana estimuladas con lipopolisacárido de P. gingivalis. Estudio in vitro; (9) Viabilidad de microorganismos periodontopáticos y bacilos entéricos después del tratamiento con ácido hipocloroso en comparación con clorhexidina; (10) Modelo in vivo de regeneración ósea mandibular a partir de células troncales dentales humanas.Departamento Administrativo de Ciencia, Tecnología e Innovación [CO] Colciencias1308-519-28960Inducción de disfunción endotelial in vitro por lipopolisacarido de bacterias periodontopaticas e inhibición de la inflamación por resolvina (rvd1) y estatina (rosuvastatina)n

Genomic structure of the native inhabitants of Peninsular Malaysia and North Borneo suggests complex human population history in Southeast Asia

Southeast Asia (SEA) is enriched with a complex history of peopling. Malaysia, which is located at the crossroads of SEA, has been recognized as one of the hubs for early human migration. To unravel the genomic complexity of the native inhabitants of Malaysia, we sequenced 12 samples from 3 indigenous populations from Peninsular Malaysia and 4 native populations from North Borneo to a high coverage of 28-37x. We showed that the Negritos from Peninsular Malaysia shared a common ancestor with the East Asians, but exhibited some level of gene flow from South Asia, while the North Borneo populations exhibited closer genetic affinity towards East Asians than the Malays. The analysis of time of divergence suggested that ancestors of Negrito were the earliest settlers in the Malay Peninsula, whom first separated from the Papuans similar to 50-33 thousand years ago (kya), followed by East Asian (similar to 40-15 kya), while the divergence time frame between North Borneo and East Asia populations predates the Austronesian expansion period implies a possible pre-Neolithic colonization. Substantial Neanderthal ancestry was confirmed in our genomes, as was observed in other East Asians. However, no significant difference was observed, in terms of the proportion of Denisovan gene flow into these native inhabitants from Malaysia. Judging from the similar amount of introgression in the Southeast Asians and East Asians, our findings suggest that the Denisovan gene flow may have occurred before the divergence of these populations and that the shared similarities are likely an ancestral component

Inferring the evolution of the major histocompatibility complex of wild pigs and peccaries using hybridisation DNA capture-based sequencing

The major histocompatibility complex (MHC) is a key genomic model region for understanding the evolution of gene families and the co-evolution between host and pathogen. To date, MHC studies have mostly focused on species from major vertebrate lineages. The evolution of MHC classical (Ia) and non-classical (Ib) genes in pigs has attracted interest because of their antigen presentation roles as part of the adaptive immune system. The pig family Suidae comprises over 18 extant species (mostly wild), but only the domestic pig has been extensively sequenced and annotated. To address this, we used a DNA-capture approach, with probes designed from the domestic pig genome, to generate MHC data for 11 wild species of pigs and their closest living family, Tayassuidae. The approach showed good efficiency for wild pigs (~80% reads mapped, ~87× coverage), compared to tayassuids (~12% reads mapped, ~4× coverage). We retrieved 145 MHC loci across both families. Phylogenetic analyses show that the class Ia and Ib genes underwent multiple duplications and diversifications before suids and tayassuids diverged from their common ancestor. The histocompatibility genes mostly form orthologous groups and there is genetic differentiation for most of these genes between Eurasian and sub-Saharan African wild pigs. Tests of selection showed that the peptide-binding region of class Ib genes was under positive selection. These findings contribute to better understanding of the evolutionary history of the MHC, specifically, the class I genes, and provide useful data for investigating the immune response of wild populations against pathogens