Impact of Amerind ancestry and FADS genetic variation on omega-3 deficiency and cardiometabolic traits in Hispanic populations.

Long chain polyunsaturated fatty acids (LC-PUFAs) have critical signaling roles that regulate dyslipidemia and inflammation. Genetic variation in the FADS gene cluster accounts for a large portion of interindividual differences in circulating and tissue levels of LC-PUFAs, with the genotypes most strongly predictive of low LC-PUFA levels at strikingly higher frequencies in Amerind ancestry populations. In this study, we examined relationships between genetic ancestry and FADS variation in 1102 Hispanic American participants from the Multi-Ethnic Study of Atherosclerosis. We demonstrate strong negative associations between Amerind genetic ancestry and LC-PUFA levels. The FADS rs174537 single nucleotide polymorphism (SNP) accounted for much of the AI ancestry effect on LC-PUFAs, especially for low levels of n-3 LC-PUFAs. Rs174537 was also strongly associated with several metabolic, inflammatory and anthropomorphic traits including circulating triglycerides (TGs) and E-selectin in MESA Hispanics. Our study demonstrates that Amerind ancestry provides a useful and readily available tool to identify individuals most likely to have FADS-related n-3 LC-PUFA deficiencies and associated cardiovascular risk.

Interpreting Clinical Trials With Omega-3 Supplements in the Context of Ancestry and FADS Genetic Variation.

Human diets in developed countries such as the US have changed dramatically over the past 75 years, leading to increased obesity, inflammation, and cardiometabolic dysfunction. Evidence over the past decade indicates that the interaction of genetic variation with changes in the intake of 18-carbon essential dietary omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA), linoleic acid (LA) and α-linolenic acid (ALA), respectively, has impacted numerous molecular and clinical phenotypes. Interactions are particularly relevant with the FADS1 and FADS2 genes, which encode key fatty acid desaturases in the pathway that converts LA and ALA to their long chain (≥20 carbons), highly unsaturated fatty acid (HUFA) counterparts. These gene by nutrient interactions affect the levels and balance of n-6 and n-3 HUFA that in turn are converted to a wide array of lipids with signaling roles, including eicosanoids, docosanoids, other oxylipins and endocannabinoids. With few exceptions, n-6 HUFA are precursors of pro-inflammatory/pro-thrombotic signaling lipids, and n-3 HUFA are generally anti-inflammatory/anti-thrombotic. We and others have demonstrated that African ancestry populations have much higher frequencies (vs. European-, Asian- or indigenous Americas-ancestry populations) of a FADS "derived" haplotype that is associated with the efficient conversion of high levels of dietary n-6 PUFA to pro-inflammatory n-6 HUFA. By contrast, an "ancestral" haplotype, carrying alleles associated with a limited capacity to synthesize HUFA, which can lead to n-3 HUFA deficiency, is found at high frequency in certain Hispanic populations and is nearly fixed in several indigenous populations from the Americas. Based on these observations, a focused secondary subgroup analysis of the VITAL n-3 HUFA supplementation trial stratifying the data based on self-reported ancestry revealed that African Americans may benefit from n-3 HUFA supplementation, and both ancestry and FADS variability should be factored into future clinical trials design.

Gibbon genome and the fast karyotype evolution of small apes.

Gibbons are small arboreal apes that display an accelerated rate of evolutionary chromosomal rearrangement and occupy a key node in the primate phylogeny between Old World monkeys and great apes. Here we present the assembly and analysis of a northern white-cheeked gibbon (Nomascus leucogenys) genome. We describe the propensity for a gibbon-specific retrotransposon (LAVA) to insert into chromosome segregation genes and alter transcription by providing a premature termination site, suggesting a possible molecular mechanism for the genome plasticity of the gibbon lineage. We further show that the gibbon genera (Nomascus, Hylobates, Hoolock and Symphalangus) experienced a near-instantaneous radiation ∼5 million years ago, coincident with major geographical changes in southeast Asia that caused cycles of habitat compression and expansion. Finally, we identify signatures of positive selection in genes important for forelimb development (TBX5) and connective tissues (COL1A1) that may have been involved in the adaptation of gibbons to their arboreal habitat.

Cellular basis of neurogenesis in the brain of crayfish, Procambarus clarkii: Neurogenic complex in the olfactory midbrain from hatchlings to adults.

Neurogenesis in the central olfactory pathway of decapod crustaceans persists throughout life. Here we describe the structural basis of neurogenesis within the olfactory deutocerebrum of the crayfish Procambarus clarkii from hatchlings to adults. Using a proliferation marker and immunostaining, we found that throughout development each hemibrain contains a neurogenic complex consisting of five parts: two proliferation zones, each within the neuronal soma clusters containing local or projection interneurons, a tail of proliferating cells extending from each proliferation zone, and an elongated clump of cells where the two tails meet. The clump of cells comprises two subdivisions joined at a nucleus-free central area. Each subdivision consists of a dense group of clump cells with small, spindle-shaped nuclei and is connected to one of the proliferation zones by a strand of fibrous material encompassing the tail of proliferating cells extending from it. We identify one proliferating cell with a large nucleus in each subdivision as a putative neuroblast. Its daughter cells migrate through the strands to the associated proliferation zones, but in the strand leading to the soma cluster of local interneurons this is masked by local proliferation. We conclude that neurogenesis in the olfactory deutocerebrum of juvenile and adult P. clarkii is based on a few neuroblasts that are associated with unique clumps of cells likely representing stem cell niches.

Social domination increases neuronal survival in the brain of juvenile crayfish Procambarus clarkii.

Olfactory cues are among the sensory inputs that crayfish use in establishing dominance hierarchies. Throughout their lives, new neurons are continuously added into brain cell clusters 9 and 10, which contain somata of olfactory local and projection interneurons, respectively. Using markers for DNA synthesis (bromodeoxyuridine) and mitosis (phospho-histone-3), we tested juvenile crayfish (Procambarus clarkii) to examine effects of pairwise social experience on proliferation and survival of cells in these brain regions. Proliferating and mitotic cells appeared within restricted neurogenic areas in both clusters and in ;tails' extending from them. These tails, embedded in tubulin-positive strands, are linked by a patch of cells. Neither cell proliferation nor mitotic activity was affected by social dominance. Cell survival of neuronal precursors was affected by dominance: compared to dominants, subordinates had fewer newborn cells surviving in cluster 9 after 14 days of social experience. Social experience also affected body growth rate, but the effect of social experience on neurogenesis remained when differences in body growth rate were statistically controlled. We conclude that social domination enhances survival of new olfactory interneuronal precursors compared to social subordination but not compared to social isolation.