Institute for Conservation and Research

San Diego, CA, United States

Institute for Conservation and Research

San Diego, CA, United States

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Gazave E.,Institute of Evolutionary Biology UPF CSIC | Gazave E.,Cornell University | Darre F.,Institute of Evolutionary Biology UPF CSIC | Darre F.,CNRS Alpine Ecology Laboratory | And 18 more authors.
Genome Research | Year: 2011

Copy number variants (CNVs) are increasingly acknowledged as an important source of evolutionary novelties in the human lineage. However, our understanding of their significance is still hindered by the lack of primate CNV data. We performed intraspecific comparative genomic hybridizations to identify loci harboring copy number variants in each of the four great apes: bonobos, chimpanzees, gorillas, and orangutans. For the first time, we could analyze differences in CNV location and frequency in these four species, and compare them with human CNVs and primate segmental duplication (SD) maps. In addition, for bonobo and gorilla, patterns of CNV and nucleotide diversity were studied in the same individuals. We show that CNVs have been subject to different selective pressures in different lineages. Evidence for purifying selection is stronger in gorilla CNVs overlapping genes, while positive selection appears to have driven the fixation of structural variants in the orangutan lineage. In contrast, chimpanzees and bonobos present high levels of common structural polymorphism, which is indicative of relaxed purifying selection together with the higher mutation rates induced by the known burst of segmental duplication in the ancestor of the African apes. Indeed, the impact of the duplication burst is noticeable by the fact that bonobo and chimpanzee share more CNVs with gorilla than expected. Finally, we identified a number of interesting genomic regions that present high-frequency CNVs in all great apes, while containing only very rare or even pathogenic structural variants in humans. © by Cold Spring Harbor Laboratory Press.


Moser A.B.,Kennedy Krieger Institute | Hey J.,Rutgers University | Dranchak P.K.,University of Southern California | Karaman M.W.,University of Southern California | And 4 more authors.
Lipids in Health and Disease | Year: 2013

Background: Humans and rodents with impaired phytanic acid (PA) metabolism can accumulate toxic stores of PA that have deleterious effects on multiple organ systems. Ruminants and certain fish obtain PA from the microbial degradation of dietary chlorophyll and/or through chlorophyll-derived precursors. In contrast, humans cannot derive PA from chlorophyll and instead normally obtain it only from meat, dairy, and fish products. Results: Captive apes and Old world monkeys had significantly higher red blood cell (RBC) PA levels relative to humans when all subjects were fed PA-deficient diets. Given the adverse health effects resulting from PA over accumulation, we investigated the molecular evolution of thirteen PA metabolism genes in apes, Old world monkeys, and New world monkeys. All non-human primate (NHP) orthologs are predicted to encode full-length proteins with the marmoset Phyh gene containing a rare, but functional, GA splice donor dinucleotide. Acox2, Scp2, and Pecr sequences had amino acid positions with accelerated substitution rates while Amacr had significant variation in evolutionary rates in apes relative to other primates. Conclusions: Unlike humans, diverse captive NHPs with PA-deficient diets rich in plant products have substantial RBC PA levels. The favored hypothesis is that NHPs can derive significant amounts of PA from the degradation of ingested chlorophyll through gut fermentation. If correct, this raises the possibility that RBC PA levels could serve as a biomarker for evaluating the digestive health of captive NHPs. Furthermore, the evolutionary rates of the several genes relevant to PA metabolism provide candidate genetic adaptations to NHP diets. © 2013 Moser et al.; licensee BioMed Central Ltd.


Moser A.B.,Kennedy Krieger Institute | Steinberg S.J.,Kennedy Krieger Institute | Watkins P.A.,Kennedy Krieger Institute | Moser H.W.,Kennedy Krieger Institute | And 6 more authors.
Lipids in Health and Disease | Year: 2011

Background: Plasmalogens are ether phospholipids required for normal mammalian developmental, physiological, and cognitive functions. They have been proposed to act as membrane antioxidants and reservoirs of polyunsaturated fatty acids as well as influence intracellular signaling and membrane dynamics. Plasmalogens are particularly enriched in cells and tissues of the human nervous, immune, and cardiovascular systems. Humans with severely reduced plasmalogen levels have reduced life spans, abnormal neurological development, skeletal dysplasia, impaired respiration, and cataracts. Plasmalogen deficiency is also found in the brain tissue of individuals with Alzheimer disease. Results: In a human and great ape cohort, we measured the red blood cell (RBC) levels of the most abundant types of plasmalogens. Total RBC plasmalogen levels were lower in humans than bonobos, chimpanzees, and gorillas, but higher than orangutans. There were especially pronounced cross-species differences in the levels of plasmalogens with a C16:0 moiety at the sn-1 position. Humans on Western or vegan diets had comparable total RBC plasmalogen levels, but the latter group showed moderately higher levels of plasmalogens with a C18:1 moiety at the sn-1 position. We did not find robust sex-specific differences in human or chimpanzee RBC plasmalogen levels or composition. Furthermore, human and great ape skin fibroblasts showed only modest differences in peroxisomal plasmalogen biosynthetic activity. Human and chimpanzee microarray data indicated that genes involved in plasmalogen biosynthesis show cross-species differential expression in multiple tissues. Conclusion: We propose that the observed differences in human and great ape RBC plasmalogens are primarily caused by their rates of biosynthesis and/or turnover. Gene expression data raise the possibility that other human and great ape cells and tissues differ in plasmalogen levels. Based on the phenotypes of humans and rodents with plasmalogen disorders, we propose that cross-species differences in tissue plasmalogen levels could influence organ functions and processes ranging from cognition to reproduction to aging. © 2011 Moser et al; licensee BioMed Central Ltd.


Watkins P.A.,Kennedy Krieger Institute | Moser A.B.,Kennedy Krieger Institute | Toomer C.B.,Kennedy Krieger Institute | Steinberg S.J.,Kennedy Krieger Institute | And 8 more authors.
BMC Physiology | Year: 2010

Background. It has been proposed that anatomical differences in human and great ape guts arose in response to species-specific diets and energy demands. To investigate functional genomic consequences of these differences, we compared their physiological levels of phytanic acid, a branched chain fatty acid that can be derived from the microbial degradation of chlorophyll in ruminant guts. Humans who accumulate large stores of phytanic acid commonly develop cerebellar ataxia, peripheral polyneuropathy, and retinitis pigmentosa in addition to other medical conditions. Furthermore, phytanic acid is an activator of the PPAR-alpha transcription factor that influences the expression of genes relevant to lipid metabolism. Results. Despite their trace dietary phytanic acid intake, all great ape species had elevated red blood cell (RBC) phytanic acid levels relative to humans on diverse diets. Unlike humans, chimpanzees showed sexual dimorphism in RBC phytanic acid levels, which were higher in males relative to females. Cultured skin fibroblasts from all species had a robust capacity to degrade phytanic acid. We provide indirect evidence that great apes, in contrast to humans, derive significant amounts of phytanic acid from the hindgut fermentation of plant materials. This would represent a novel reduction of metabolic activity in humans relative to the great apes. Conclusion. We identified differences in the physiological levels of phytanic acid in humans and great apes and propose this is causally related to their gut anatomies and microbiomes. Phytanic acid levels could contribute to cross-species and sex-specific differences in human and great ape transcriptomes, especially those related to lipid metabolism. Based on the medical conditions caused by phytanic acid accumulation, we suggest that differences in phytanic acid metabolism could influence the functions of human and great ape nervous, cardiovascular, and skeletal systems. © 2010 Watkins et al; licensee BioMed Central Ltd.


PubMed | SeaWorld and Busch Gardens Reproductive Research Center and Institute for Conservation and Research
Type: | Journal: Andrology | Year: 2016

Circulating concentrations of testosterone and its precursor androstenedione, as well as dehydroepiandrosterone (DHEA) and the adrenal hormones cortisol and corticosterone were measured at monthly intervals in 14 male killer whales (Orcinus orca) aged 0.8-38years. Analyses were performed for examination of the relationships of age, sexual maturation status (STATUS), season, and environmental temperature (monthly air ambient temperature, A-TEMP) with hormone production using a mixed effects linear regression model with animal ID as the random variable. Hormone profiles, derived from enzyme immunoassay procedures validated herein, established that simultaneous up-regulation of androstenedione and testosterone production occurs at puberty, when males are aged 8-12years. Androgen (testosterone and androstenedione) production in pubertal and adult males was influenced by season, with highest (p<0.01) concentrations observed in spring and summer months. A significant effect of STATUS and season on DHEA production was also documented, with higher (p<0.05) concentrations in pubertal and adult males compared to juvenile males, and higher (p<0.05) concentrations in the months of summer than the fall. Among adult males (13years), those classified as aged (31years) had concentrations of testosterone and both glucocorticoids that were lower (p<0.05), and those of androstenedione that were higher (p<0.05) than their younger counterparts. The cortisol:corticosterone ratio for adult males was 7:1, and both glucocorticoids were affected by STATUS (p<0.05), but not season or A-TEMP. Results of this research enhance our understanding of reproductive and adrenocortical function in healthy male killer whales and provide baseline profiles of hormone production for use in the species health assessment and conservation.

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