Bean Genome Diversity Reveals the Genomic Consequences of Speciation, Adaptation, and Domestication

Here we review whether genomic islands of speciation are repeatedly more prone to harbor within-species differentiation due to genomic features, such as suppressed recombination, smaller effective population size, and increased drift, across repeated hierarchically nested levels of divergence. Our discussion focuses on two species of Phaseolus beans with strong genepool and population substructure and multiple independent domestications each. We overview regions of species-associated divergence, as well as divergence recovered in within-species between-genepool comparisons and in within-genepool wild-cultivated comparisons. We discuss whether regions with overall high relative differentiation coincide with sections of low SNP density and with between-species pericentric inversions, since these convergences would suggest that shared variants are being recurrently fixed at replicated comparisons, and in a similar manner across different hierarchically nested levels of divergence, likely as the result of genomic features that make certain regions more prone to accumulate islands of speciation as well as within-species divergence. We conclude that neighboring signatures of speciation, adaptation, and domestication in Phaseolus beans seem to be influenced by ubiquitous genomic constrains, which may continue shaping, fortuitously, genomic differentiation at various other scales of divergence. This pattern also suggests that genomic regions important for adaptation may frequently be sheltered from recombination

Does the Genomic Landscape of Species Divergence in Phaseolus Beans Coerce Parallel Signatures of Adaptation and Domestication?

Exploring the genomic architecture of species and populations divergence aids understanding how lineages evolve and adapt, and ultimately can show the repeatability of evolutionary processes. Yet, the genomic signatures associated with divergence are still relatively unexplored, leading to a knowledge gap on whether species divergence ultimately differs in its genetic architecture from divergence at other spatial scales (i.e., populations, ecotypes). Our goal in this research was to determine whether genomic islands of speciation are more prone to harbor within-species differentiation due to genomic features, suppressed recombination, smaller effective population size or increased drift, across repeated hierarchically nested levels of divergence. We used two species of Phaseolus beans with strong genepool and population sub-structure produced by multiple independent domestications each especially in Andean and Mesoamerican / Middle American geographies. We genotyped 22,531 GBS-derived SNP markers in 209 individuals of wild and cultivated Phaseolus vulgaris and Phaseolus lunatus. We identified six regions for species-associated divergence. Out of these divergence peaks, 21% were recovered in the four within-species between-genepool comparisons and in the five within-genepool wild-cultivated comparisons (some of the latter did retrieve genuine signatures of the well described multiple domestication syndromes). However, genomic regions with overall high relative differentiation (measured by FST) coincided with regions of low SNP density and regions of elevated delta divergence between-genepools (ΔDiv), independent of the scale of divergence. The divergence in chromosome Pv10 further coincided with a between-species pericentric inversion. These convergences suggest that shared variants are being recurrently fixed at replicated regions of the genome, and in a similar manner across different hierarchically nested levels of divergence, likely as result of genomic features that make certain regions more prone to accumulate islands of speciation and within-species divergence. In summary, neighboring signatures of speciation, adaptation and domestication in Phaseolus beans are influenced by ubiquitous genomic constrains, which may continue to fortuitously shape genomic differentiation at various others scales of divergence

Hypoxia compromises the mitochondrial metabolism of Alzheimer’s disease microglia via HIF1

Genetic Alzheimer’s disease (AD) risk factors associate with reduced defensive amyloid β plaque-associated microglia (AβAM), but the contribution of modifiable AD risk factors to microglial dysfunction is unknown. In AD mouse models, we observe concomitant activation of the hypoxia-inducible factor 1 (HIF1) pathway and transcription of mitochondrial-related genes in AβAM, and elongation of mitochondria, a cellular response to maintain aerobic respiration under low nutrient and oxygen conditions. Overactivation of HIF1 induces microglial quiescence in cellulo, with lower mitochondrial respiration and proliferation. In vivo, overstabilization of HIF1, either genetically or by exposure to systemic hypoxia, reduces AβAM clustering and proliferation and increases Aβ neuropathology. In the human AD hippocampus, upregulation of HIF1α and HIF1 target genes correlates with reduced Aβ plaque microglial coverage and an increase of Aβ plaque-associated neuropathology. Thus, hypoxia (a modifiable AD risk factor) hijacks microglial mitochondrial metabolism and converges with genetic susceptibility to cause AD microglial dysfunction.Instituto de Salud Carlos III CD09/0007, PI18/01556, PI18/01557Ministerio de Educación, Cultura y Deporte FPU14/02115, AP2010‐1598, FPU16/02050, FPU15/02898, BES-2010-033886Ministerio de Economia, Industria y Competitividad SAF2012‐33816, SAF2015‐64111‐R, SAF2017-90794-REDT, PIE13/0004, BFU2016-76872-R, BES-2011-047721Junta de Andalucía P12‐CTS‐2138, P12‐CTS‐2232, UMA18-FEDERJA-211, US‐126273

Database of spatial distribution of non indigenous species in Spanish marine waters

Research in marine Spanish waters are focused on several actions to achieve an effectively management on protected areas, with the active participation of the stakeholders and research as basic tools for decision-making. Among these actions, there is one about the knowledge and control on NIS. One of its objectives is the creation of NIS factsheets, which are going to be added to the National Marine Biodiversity Geographical System (GIS) providing complementary information about taxonomic classification, common names, taxonomic synonyms, species illustrations, identification morphological characters, habitat in the native and introduced regions, biological and ecological traits, GenBank DNA sequences, world distribution, first record and evolution in the introduced areas, likely pathways of introduction, effects in the habitats and interaction with native species, and potential management measures to apply. The database will also provide data for (1) the European online platforms, (2) the environmental assessment for the Descriptor 2 (D2-NIS) of the EU Marine Strategy Framework Directive (MSFD), as well as (3) supporting decisions made by stakeholders. It is the result of extensive collaboration among scientist, manager’s and citizen science in the Spanish North-Atlantic, South-Atlantic, Gibraltar Strait-Alboran, Levantine-Balearic and Canary Islands marine divisions, providing an updated overview of the spatial distribution of relevant extended and invasive NIS of recent and established NIS introduced by maritime transport and aquaculture pathways, as well as on cryptogenic or native species in expansion due to the climatic water warming trend

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Testing Domestication Scenarios of Lima Bean (Phaseolus lunatus L.) in Mesoamerica: Insights from Genome-Wide Genetic Markers

Plant domestication can be seen as a long-term process that involves a complex interplay among demographic processes and evolutionary forces. Previous studies have suggested two domestication scenarios for Lima bean in Mesoamerica: two separate domestication events, one from gene pool MI in central-western Mexico and another one from gene pool MII in the area Guatemala-Costa Rica, or a single domestication from gene pool MI in central-western Mexico followed by post-domestication gene flow with wild populations. In this study we evaluated the genetic structure of the wild gene pool and tested these two competing domestication scenarios of Lima bean in Mesoamerica by applying an ABC approach to a set of genome-wide SNP markers. The results confirm the existence of three gene pools in wild Lima bean, two Mesoamerican gene pools (MI and MII) and the Andean gene pool (AI), and suggest the existence of another gene pool in central Colombia. The results indicate that although both domestication scenarios may be supported by genetic data, higher statistical support was given to the single domestication scenario in central-western Mexico followed by admixture with wild populations. Domestication would have involved strong founder effects reflected in loss of genetic diversity and increased LD levels in landraces. Genomic regions affected by selection were detected and these may harbor candidate genes related to domestication