SYNPHONI: scale-free and phylogeny-aware reconstruction of synteny conservation and transformation across animal genomes.

SUMMARY: Current approaches detect conserved genomic order either at chromosomal (macrosynteny) or at subchromosomal scales (microsynteny). The latter generally requires collinearity and hard thresholds on syntenic region size, thus excluding a major proportion of syntenies with recent expansions or minor rearrangements. 'SYNPHONI' bridges the gap between micro- and macrosynteny detection, providing detailed information on both synteny conservation and transformation throughout the evolutionary history of animal genomes. AVAILABILITY AND IMPLEMENTATION: Source code is freely available at https://github.com/nsmro/SYNPHONI, implemented in Python 3.9. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Emergence of distinct syntenic density regimes is associated with early metazoan genomic transitions.

BACKGROUND: Animal genomes are strikingly conserved in terms of local gene order (microsynteny). While some of these microsyntenies have been shown to be coregulated or to form gene regulatory blocks, the diversity of their genomic and regulatory properties across the metazoan tree of life remains largely unknown. RESULTS: Our comparative analyses of 49 animal genomes reveal that the largest gains of synteny occurred in the last common ancestor of bilaterians and cnidarians and in that of bilaterians. Depending on their node of emergence, we further show that novel syntenic blocks are characterized by distinct functional compositions (Gene Ontology terms enrichment) and gene density properties, such as high, average and low gene density regimes. This is particularly pronounced among bilaterian novel microsyntenies, most of which fall into high gene density regime associated with higher gene coexpression levels. Conversely, a majority of vertebrate novel microsyntenies display a low gene density regime associated with lower gene coexpression levels. CONCLUSIONS: Our study provides first evidence for evolutionary transitions between different modes of microsyntenic block regulation that coincide with key events of metazoan evolution. Moreover, the microsyntenic profiling strategy and interactive online application (Syntenic Density Browser, available at: http://synteny.csb.univie.ac.at/ ) we present here can be used to explore regulatory properties of microsyntenic blocks and predict their coexpression in a wide-range of animal genomes.

Natal origin of Namibian grey whale implies new distance record for in-water migration.

We use genomics to identify the natal origin of a grey whale found in the South Atlantic, at least 20 000 km from the species core range (halfway around the world). The data indicate an origin in the North Pacific, possibly from the endangered western North Pacific population, thought to include only approximately 200 individuals. This contributes to our understanding of Atlantic sightings of this species known primarily from the North Pacific, and could have conservation implications if grey whales have the potential for essentially global dispersion. More broadly, documenting and understanding rare extreme migration events have potential implications for the understanding of how a species may be able to respond to global change.

Genomics of post-bottleneck recovery in the northern elephant seal.

Populations and species are threatened by human pressure, but their fate is variable. Some depleted populations, such as that of the northern elephant seal (Mirounga angustirostris), recover rapidly even when the surviving population was small. The northern elephant seal was hunted extensively and taken by collectors between the early 1800s and 1892, suffering an extreme population bottleneck as a consequence. Recovery was rapid and now there are over 200,000 individuals. We sequenced 260 modern and 8 historical northern elephant seal nuclear genomes to assess the impact of the population bottleneck on individual northern elephant seals and to better understand their recovery. Here we show that inbreeding, an increase in the frequency of alleles compromised by lost function, and allele frequency distortion, reduced the fitness of breeding males and females, as well as the performance of adult females on foraging migrations. We provide a detailed investigation of the impact of a severe bottleneck on fitness at the genomic level and report on the role of specific gene systems.

Robust 3D modeling reveals spatiosyntenic properties of animal genomes.

Animal genomes are organized into chromosomes that are remarkably conserved in their gene content, forming distinct evolutionary units (synteny). Using versatile chromosomal modeling, we infer three-dimensional topology of genomes from representative clades spanning the earliest animal diversification. We apply a partitioning approach using interaction spheres to compensate for varying quality of topological data. Using comparative genomics approaches, we test whether syntenic signal at gene pair, local, and whole chromosomal scale is reflected in the reconstructed spatial organization. We identify evolutionarily conserved three-dimensional networks at all syntenic scales revealing novel evolutionarily maintained interactors associated with known conserved local gene linkages (such as hox). We thus present evidence for evolutionary constraints that are associated with three-, rather than just two-, dimensional animal genome organization, which we term spatiosynteny. As more accurate topological data become available, together with validation approaches, spatiosynteny may become relevant in understanding the functionality behind the observed conservation of animal chromosomes.

Endothelial and systemic upregulation of miR-34a-5p fine-tunes senescence in progeria.

Endothelial defects significantly contribute to cardiovascular pathology in the premature aging disease Hutchinson-Gilford progeria syndrome (HGPS). Using an endothelium-specific progeria mouse model, we identify a novel, endothelium-specific microRNA (miR) signature linked to the p53-senescence pathway and a senescence-associated secretory phenotype (SASP). Progerin-expressing endothelial cells exert profound cell-non-autonomous effects initiating senescence in non-endothelial cell populations and causing immune cell infiltrates around blood vessels. Comparative miR expression analyses revealed unique upregulation of senescence-associated miR34a-5p in endothelial cells with strong accumulation at atheroprone aortic arch regions but also, in whole cardiac- and lung tissues as well as in the circulation of progeria mice. Mechanistically, miR34a-5p knockdown reduced not only p53 levels but also late-stage senescence regulator p16 with no effect on p21 levels, while p53 knockdown reduced miR34a-5p and partially rescued p21-mediated cell cycle inhibition with a moderate effect on SASP. These data demonstrate that miR34a-5p reinforces two separate senescence regulating branches in progerin-expressing endothelial cells, the p53- and p16-associated pathways, which synergistically maintain a senescence phenotype that contributes to cardiovascular pathology. Thus, the key function of circulatory miR34a-5p in endothelial dysfunction-linked cardiovascular pathology offers novel routes for diagnosis, prognosis and treatment for cardiovascular aging in HGPS and potentially geriatric patients.

Chromosome-scale genome assembly of the brown anole (Anolis sagrei), an emerging model species.

Rapid technological improvements are democratizing access to high quality, chromosome-scale genome assemblies. No longer the domain of only the most highly studied model organisms, now non-traditional and emerging model species can be genome-enabled using a combination of sequencing technologies and assembly software. Consequently, old ideas built on sparse sampling across the tree of life have recently been amended in the face of genomic data drawn from a growing number of high-quality reference genomes. Arguably the most valuable are those long-studied species for which much is already known about their biology; what many term emerging model species. Here, we report a highly complete chromosome-scale genome assembly for the brown anole, Anolis sagrei - a lizard species widely studied across a variety of disciplines and for which a high-quality reference genome was long overdue. This assembly exceeds the vast majority of existing reptile and snake genomes in contiguity (N50 = 253.6 Mb) and annotation completeness. Through the analysis of this genome and population resequence data, we examine the history of repetitive element accumulation, identify the X chromosome, and propose a hypothesis for the evolutionary history of fusions between autosomes and the X that led to the sex chromosomes of A. sagrei.

Does color matter? Molecular and ecological divergence in four sympatric color morphs of a coral reef fish.

Non-sex-linked color polymorphism is common in animals and can be maintained in populations via balancing selection or, when under diversifying selection, can promote divergence. Despite their potential importance in ecological interactions and the evolution of biodiversity, their function and the mechanisms by which these polymorphisms are maintained are still poorly understood. Here, we combine field observations with life history and molecular data to compare four sympatric color morphs of the coral reef fish Paracirrhites forsteri (family Cirrhitidae) in the central Red Sea. Our findings verify that the color morphs are not sex-limited, inhabit the same reefs, and do not show clear signs of avoidance or aggression among them. A barcoding approach based on 1,276 bp of mitochondrial DNA could not differentiate the color morphs. However, when 36,769 SNPs were considered, we found low but significant population structure. Focusing on 1,121 F ST outliers, we recovered distinct population clusters that corresponded to shifts in allele frequencies with each color morph harboring unique alleles. Genetic divergence at these outlier loci is accompanied by differences in growth and marginal variation in microhabitat preference. Together, life history and molecular analysis suggest subtle divergence between the color morphs in this population, the causes for which remain elusive.

Genomics of habitat choice and adaptive evolution in a deep-sea fish.

Intraspecific diversity promotes evolutionary change, and when partitioned among geographic regions or habitats can form the basis for speciation. Marine species live in an environment that can provide as much scope for diversification in the vertical as in the horizontal dimension. Understanding the relevant mechanisms will contribute significantly to our understanding of eco-evolutionary processes and effective biodiversity conservation. Here, we provide an annotated genome assembly for the deep-sea fish Coryphaenoides rupestris and re-sequencing data to show that differentiation at non-synonymous sites in functional loci distinguishes individuals living at different depths, independent of horizontal spatial distance. Our data indicate disruptive selection at these loci; however, we find no clear evidence for differentiation at neutral loci that may indicate assortative mating. We propose that individuals with distinct genotypes at relevant loci segregate by depth as they mature (supported by survey data), which may be associated with ecotype differentiation linked to distinct phenotypic requirements at different depths.