W hile longitudinal and latitudinal habitat transitions have been proposed to define marine communities and promote intraspecific differentiation 1-3 , little is known about the importance of transitions along ocean depth gradients 4,5 , although substantial changes in species assemblages with depth have been recorded (for example, ref. 6 ), and relatively narrow depth ranges may distinguish closely related species (for example, refs 7,8 ). Understanding the relevant mechanisms will contribute significantly to our understanding of eco-evolutionary processes and the origin of marine biodiversity. We chose the roundnose grenadier (Coryphaenoides rupestris) as a model system because it is a widespread species that can inhabit a comparatively broad range of depths 9 from ~180 m to 2,600 m. It is a batch spawner, producing up to 69,000 pelagic eggs per female 10 . It has a spawning season peaking in autumn 11 (recent observations were in September at 1,500 m; ref. 12 ), preys on fish, cephalopods and invertebrates in both benthic and pelagic habitats 13 , and shows minor genetic differentiation across its geographic range [14][15][16] .Adaptation to habitat can occur among populations within a species, and if disruptive selection is associated with assortative mating has the potential to promote incipient speciation through ecological processes in sympatry 17 . When environmental change exposes new habitats and niche potential, adaptive radiations may rapidly generate a new lineage of species 18,19 . To the extent that differential selection can retain polymorphisms within or among populations, this may facilitate the process of adaptive radiation. Here, we focus on one of the key habitat transitions in the oceans-between the photic mesopelagic region and the aphotic regions below (together with the more contiguous changes associated with increasing depth). There is the potential for species (such as the roundnose grenadier), whose habitat range extends across this boundary or along the depth gradient, to experience differential selective pressures. We tested hypotheses about adaptation to these deep-sea habitats using genome sequence data together with data on the ecology and life history of the subject species. We found that juvenile fish of this species are found primarily in relatively shallow depths (near the transition between the mesopelagic and bathypelagic zones) and then migrate as they mature to different depths, and this is strongly associated with their genotype at a set of functional loci. In particular, all adults below ~1,800 m share the same homozygous genotype at each locus. There is evidence for strong selection maintaining this difference, but no clear evidence for differentiation driven by assortative mating. Results and discussionWe produced an annotated reference genome for C. rupestris with a total length of 0.829 gigabase pairs, a mean depth of 104× and an N50 of 159,738 (see Supplementary Methods for details). We used this draft genome to map 60 additional genomes sequenced to a mean depth ...

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.