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1.
Proc Natl Acad Sci U S A ; 119(8)2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35131902

RESUMO

Weather-related disasters are increasing in frequency and severity, leaving survivors to cope with ensuing mental, financial, and physical hardships. This adversity can exacerbate existing morbidities, trigger new ones, and increase the risk of mortality-features that are also characteristic of advanced age-inviting the hypothesis that extreme weather events may accelerate aging. To test this idea, we examined the impact of Hurricane Maria and its aftermath on immune cell gene expression in large, age-matched, cross-sectional samples from free-ranging rhesus macaques (Macaca mulatta) living on an isolated island. A cross section of macaques was sampled 1 to 4 y before (n = 435) and 1 y after (n = 108) the hurricane. Hurricane Maria was significantly associated with differential expression of 4% of immune-cell-expressed genes, and these effects were correlated with age-associated alterations in gene expression. We further found that individuals exposed to the hurricane had a gene expression profile that was, on average, 1.96 y older than individuals that were not-roughly equivalent to an increase in 7 to 8 y of a human life. Living through an intense hurricane and its aftermath was associated with expression of key immune genes, dysregulated proteostasis networks, and greater expression of inflammatory immune cell-specific marker genes. Together, our findings illuminate potential mechanisms through which the adversity unleashed by extreme weather and potentially other natural disasters might become biologically embedded, accelerate age-related molecular immune phenotypes, and ultimately contribute to earlier onset of disease and death.


Assuntos
Envelhecimento/imunologia , Macaca/imunologia , Sobreviventes/psicologia , Fatores Etários , Animais , Estudos Transversais , Tempestades Ciclônicas , Desastres , Desastres Naturais/mortalidade , Fatores de Risco
2.
Mol Ecol ; : e17445, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39032090

RESUMO

Phenotypic aging is ubiquitous across mammalian species, suggesting shared underlying mechanisms of aging. Aging is linked to molecular changes to DNA methylation and gene expression, and environmental factors, such as severe external challenges or adversities, can moderate these age-related changes. Yet, it remains unclear whether environmental adversities affect gene regulation via the same molecular pathways as chronological, or 'primary', aging. Investigating molecular aging in naturalistic animal populations can fill this gap by providing insight into shared molecular mechanisms of aging and the effects of a greater diversity of environmental adversities - particularly those that can be challenging to study in humans or laboratory organisms. Here, we characterised molecular aging - specifically, CpG methylation - in a sample of free-ranging rhesus macaques living off the coast of Puerto Rico (n samples = 571, n individuals = 499), which endured a major hurricane during our study. Age was associated with methylation at 78,661 sites (31% of all sites tested). Age-associated hypermethylation occurred more frequently in areas of active gene regulation, while hypomethylation was enriched in regions that show less activity in immune cells, suggesting these regions may become de-repressed in older individuals. Age-associated hypomethylation also co-occurred with increased chromatin accessibility while hypermethylation showed the opposite trend, hinting at a coordinated, multi-level loss of epigenetic stability during aging. We detected 32,048 CpG sites significantly associated with exposure to a hurricane, and these sites overlapped age-associated sites, most strongly in regulatory regions and most weakly in quiescent regions. Together, our results suggest that environmental adversity may contribute to aging-related molecular phenotypes in regions of active gene transcription, but that primary aging has specific signatures in non-regulatory regions.

3.
Proc Natl Acad Sci U S A ; 118(7)2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33574059

RESUMO

Ecological flexibility, extended lifespans, and large brains have long intrigued evolutionary biologists, and comparative genomics offers an efficient and effective tool for generating new insights into the evolution of such traits. Studies of capuchin monkeys are particularly well situated to shed light on the selective pressures and genetic underpinnings of local adaptation to diverse habitats, longevity, and brain development. Distributed widely across Central and South America, they are inventive and extractive foragers, known for their sensorimotor intelligence. Capuchins have among the largest relative brain size of any monkey and a lifespan that exceeds 50 y, despite their small (3 to 5 kg) body size. We assemble and annotate a de novo reference genome for Cebus imitator Through high-depth sequencing of DNA derived from blood, various tissues, and feces via fluorescence-activated cell sorting (fecalFACS) to isolate monkey epithelial cells, we compared genomes of capuchin populations from tropical dry forests and lowland rainforests and identified population divergence in genes involved in water balance, kidney function, and metabolism. Through a comparative genomics approach spanning a wide diversity of mammals, we identified genes under positive selection associated with longevity and brain development. Additionally, we provide a technological advancement in the use of noninvasive genomics for studies of free-ranging mammals. Our intra- and interspecific comparative study of capuchin genomics provides insights into processes underlying local adaptation to diverse and physiologically challenging environments, as well as the molecular basis of brain evolution and longevity.


Assuntos
Adaptação Fisiológica , Encéfalo/crescimento & desenvolvimento , Cebus/genética , Genoma , Longevidade/genética , Animais , Evolução Molecular , Citometria de Fluxo/métodos , Florestas , Genômica/métodos
4.
EMBO Rep ; 22(10): e53739, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34477287

RESUMO

The COVID-19 pandemic has rekindled debates about gain-of-function experiments. This is an opportunity to clearly define safety risks and appropriate countermeasures.


Assuntos
COVID-19 , Contenção de Riscos Biológicos , Mutação com Ganho de Função , Humanos , Pandemias , SARS-CoV-2
5.
J Hand Surg Am ; 47(8): 772-782, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35641389

RESUMO

Degenerative disorders of the wrist may affect isolated joints and inhibit normal functions of the wrist secondary to pain and stiffness. These processes that affect only the radiocarpal joint may be secondary to posttraumatic osteoarthritis, primary osteoarthritis, or rheumatoid arthritis. Radiocarpal wrist arthrodesis may help preserve some of the native wrist kinematics while alleviating pain and improving the range of motion. However, the surgeon must ensure that the patient's pathologic process primarily affects the radiocarpal articulations while relatively sparing the midcarpal articulations. Depending on the location of the pathology, isolated radiolunate or radioscapholunate arthrodesis have been described to preserve some motion in the midcarpal joint. To maximize motion in the midcarpal joint after radiocarpal arthrodesis, techniques for distal scaphoid and triquetrum excision have been described. We report patient outcomes for various techniques and describe our preferred technique for radioscapholunate arthrodesis using distal scaphoid excision.


Assuntos
Articulações do Carpo , Doenças Musculoesqueléticas , Osteoartrite , Osso Escafoide , Artrodese/métodos , Articulações do Carpo/diagnóstico por imagem , Articulações do Carpo/cirurgia , Humanos , Osteoartrite/diagnóstico por imagem , Osteoartrite/cirurgia , Dor , Amplitude de Movimento Articular , Osso Escafoide/diagnóstico por imagem , Osso Escafoide/cirurgia , Articulação do Punho/diagnóstico por imagem , Articulação do Punho/cirurgia
6.
Proc Natl Acad Sci U S A ; 114(42): E8885-E8894, 2017 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-28928148

RESUMO

Here, we present a transformational approach to genome engineering of herpes simplex virus type 1 (HSV-1), which has a large DNA genome, using synthetic genomics tools. We believe this method will enable more rapid and complex modifications of HSV-1 and other large DNA viruses than previous technologies, facilitating many useful applications. Yeast transformation-associated recombination was used to clone 11 fragments comprising the HSV-1 strain KOS 152 kb genome. Using overlapping sequences between the adjacent pieces, we assembled the fragments into a complete virus genome in yeast, transferred it into an Escherichia coli host, and reconstituted infectious virus following transfection into mammalian cells. The virus derived from this yeast-assembled genome, KOSYA, replicated with kinetics similar to wild-type virus. We demonstrated the utility of this modular assembly technology by making numerous modifications to a single gene, making changes to two genes at the same time and, finally, generating individual and combinatorial deletions to a set of five conserved genes that encode virion structural proteins. While the ability to perform genome-wide editing through assembly methods in large DNA virus genomes raises dual-use concerns, we believe the incremental risks are outweighed by potential benefits. These include enhanced functional studies, generation of oncolytic virus vectors, development of delivery platforms of genes for vaccines or therapy, as well as more rapid development of countermeasures against potential biothreats.


Assuntos
Genômica/métodos , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/patogenicidade , Animais , Proteínas de Bactérias/genética , Chlorocebus aethiops , Cromossomos Artificiais Bacterianos , Escherichia coli/genética , Genoma Viral , Proteínas Luminescentes/genética , Proteínas Recombinantes de Fusão/genética , Recombinação Genética , Saccharomyces cerevisiae/genética , Células Vero , Montagem de Vírus/genética
7.
Genome Res ; 25(3): 435-44, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25654978

RESUMO

The availability of genetically tractable organisms with simple genomes is critical for the rapid, systems-level understanding of basic biological processes. Mycoplasma bacteria, with the smallest known genomes among free-living cellular organisms, are ideal models for this purpose, but the natural versions of these cells have genome complexities still too great to offer a comprehensive view of a fundamental life form. Here we describe an efficient method for reducing genomes from these organisms by identifying individually deletable regions using transposon mutagenesis and progressively clustering deleted genomic segments using meiotic recombination between the bacterial genomes harbored in yeast. Mycoplasmal genomes subjected to this process and transplanted into recipient cells yielded two mycoplasma strains. The first simultaneously lacked eight singly deletable regions of the genome, representing a total of 91 genes and ∼ 10% of the original genome. The second strain lacked seven of the eight regions, representing 84 genes. Growth assay data revealed an absence of genetic interactions among the 91 genes under tested conditions. Despite predicted effects of the deletions on sugar metabolism and the proteome, growth rates were unaffected by the gene deletions in the seven-deletion strain. These results support the feasibility of using single-gene disruption data to design and construct viable genomes lacking multiple genes, paving the way toward genome minimization. The progressive clustering method is expected to be effective for the reorganization of any mega-sized DNA molecules cloned in yeast, facilitating the construction of designer genomes in microbes as well as genomic fragments for genetic engineering of higher eukaryotes.


Assuntos
Bactérias/genética , Transferência Genética Horizontal , Genoma Bacteriano , Família Multigênica , Deleção de Sequência , Leveduras/genética , Elementos de DNA Transponíveis
8.
Genome Res ; 25(12): 1921-33, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26377836

RESUMO

We describe a genome reference of the African green monkey or vervet (Chlorocebus aethiops). This member of the Old World monkey (OWM) superfamily is uniquely valuable for genetic investigations of simian immunodeficiency virus (SIV), for which it is the most abundant natural host species, and of a wide range of health-related phenotypes assessed in Caribbean vervets (C. a. sabaeus), whose numbers have expanded dramatically since Europeans introduced small numbers of their ancestors from West Africa during the colonial era. We use the reference to characterize the genomic relationship between vervets and other primates, the intra-generic phylogeny of vervet subspecies, and genome-wide structural variations of a pedigreed C. a. sabaeus population. Through comparative analyses with human and rhesus macaque, we characterize at high resolution the unique chromosomal fission events that differentiate the vervets and their close relatives from most other catarrhine primates, in whom karyotype is highly conserved. We also provide a summary of transposable elements and contrast these with the rhesus macaque and human. Analysis of sequenced genomes representing each of the main vervet subspecies supports previously hypothesized relationships between these populations, which range across most of sub-Saharan Africa, while uncovering high levels of genetic diversity within each. Sequence-based analyses of major histocompatibility complex (MHC) polymorphisms reveal extremely low diversity in Caribbean C. a. sabaeus vervets, compared to vervets from putatively ancestral West African regions. In the C. a. sabaeus research population, we discover the first structural variations that are, in some cases, predicted to have a deleterious effect; future studies will determine the phenotypic impact of these variations.


Assuntos
Chlorocebus aethiops/genética , Genoma , Genômica , Animais , Chlorocebus aethiops/classificação , Coloração Cromossômica , Biologia Computacional/métodos , Evolução Molecular , Rearranjo Gênico , Variação Genética , Genômica/métodos , Cariótipo , Complexo Principal de Histocompatibilidade/genética , Anotação de Sequência Molecular , Filogenia , Filogeografia
9.
Am J Primatol ; 80(10): e22873, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29931777

RESUMO

The neuropeptides oxytocin (OT) and arginine vasopressin (AVP) influence pair bonding, attachment, and sociality, as well as anxiety and stress responses in humans and other mammals. The effects of these peptides are mediated by genetic variability in their associated receptors, OXTR and the AVPR gene family. However, the role of these genes in regulating social behaviors in non-human primates is not well understood. To address this question, we examined whether genetic variation in the OT receptor gene OXTR and the AVP receptor genes AVPR1A and AVPR1B influence naturally-occurring social behavior in free-ranging rhesus macaques-gregarious primates that share many features of their biology and social behavior with humans. We assessed rates of social behavior across 3,250 hr of observational behavioral data from 201 free-ranging rhesus macaques on Cayo Santiago island in Puerto Rico, and used genetic sequence data to identify 25 OXTR, AVPR1A, and AVPR1B single-nucleotide variants (SNVs) in the population. We used an animal model to estimate the effects of 12 SNVs (n = 3 OXTR; n = 5 AVPR1A; n = 4 AVPR1B) on rates of grooming, approaches, passive contact, contact aggression, and non-contact aggression, given and received. Though we found evidence for modest heritability of these behaviors, estimates of effect sizes of the selected SNVs were close to zero, indicating that common OXTR and AVPR variation contributed little to social behavior in these animals. Our results are consistent with recent findings in human genetics that the effects of individual common genetic variants on complex phenotypes are generally small.


Assuntos
Macaca mulatta/fisiologia , Receptores de Ocitocina/genética , Receptores de Vasopressinas/genética , Comportamento Social , Agressão , Animais , Comportamento Animal/fisiologia , Feminino , Genótipo , Asseio Animal , Macaca mulatta/genética , Masculino , Polimorfismo de Nucleotídeo Único , Porto Rico
10.
Proc Natl Acad Sci U S A ; 112(48): 14936-41, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26627243

RESUMO

Rhodnius prolixus not only has served as a model organism for the study of insect physiology, but also is a major vector of Chagas disease, an illness that affects approximately seven million people worldwide. We sequenced the genome of R. prolixus, generated assembled sequences covering 95% of the genome (∼ 702 Mb), including 15,456 putative protein-coding genes, and completed comprehensive genomic analyses of this obligate blood-feeding insect. Although immune-deficiency (IMD)-mediated immune responses were observed, R. prolixus putatively lacks key components of the IMD pathway, suggesting a reorganization of the canonical immune signaling network. Although both Toll and IMD effectors controlled intestinal microbiota, neither affected Trypanosoma cruzi, the causal agent of Chagas disease, implying the existence of evasion or tolerance mechanisms. R. prolixus has experienced an extensive loss of selenoprotein genes, with its repertoire reduced to only two proteins, one of which is a selenocysteine-based glutathione peroxidase, the first found in insects. The genome contained actively transcribed, horizontally transferred genes from Wolbachia sp., which showed evidence of codon use evolution toward the insect use pattern. Comparative protein analyses revealed many lineage-specific expansions and putative gene absences in R. prolixus, including tandem expansions of genes related to chemoreception, feeding, and digestion that possibly contributed to the evolution of a blood-feeding lifestyle. The genome assembly and these associated analyses provide critical information on the physiology and evolution of this important vector species and should be instrumental for the development of innovative disease control methods.


Assuntos
Adaptação Fisiológica/genética , Doença de Chagas , Interações Hospedeiro-Parasita/genética , Insetos Vetores , Rhodnius , Trypanosoma cruzi/fisiologia , Animais , Sequência de Bases , Transferência Genética Horizontal , Humanos , Insetos Vetores/genética , Insetos Vetores/parasitologia , Dados de Sequência Molecular , Rhodnius/genética , Rhodnius/parasitologia , Wolbachia/genética
11.
Proc Natl Acad Sci U S A ; 111(48): 17230-5, 2014 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-25385592

RESUMO

Little is known about the genetic changes that distinguish domestic cat populations from their wild progenitors. Here we describe a high-quality domestic cat reference genome assembly and comparative inferences made with other cat breeds, wildcats, and other mammals. Based upon these comparisons, we identified positively selected genes enriched for genes involved in lipid metabolism that underpin adaptations to a hypercarnivorous diet. We also found positive selection signals within genes underlying sensory processes, especially those affecting vision and hearing in the carnivore lineage. We observed an evolutionary tradeoff between functional olfactory and vomeronasal receptor gene repertoires in the cat and dog genomes, with an expansion of the feline chemosensory system for detecting pheromones at the expense of odorant detection. Genomic regions harboring signatures of natural selection that distinguish domestic cats from their wild congeners are enriched in neural crest-related genes associated with behavior and reward in mouse models, as predicted by the domestication syndrome hypothesis. Our description of a previously unidentified allele for the gloving pigmentation pattern found in the Birman breed supports the hypothesis that cat breeds experienced strong selection on specific mutations drawn from random bred populations. Collectively, these findings provide insight into how the process of domestication altered the ancestral wildcat genome and build a resource for future disease mapping and phylogenomic studies across all members of the Felidae.


Assuntos
Animais Domésticos/genética , Animais Selvagens/genética , Gatos/genética , Genoma/genética , Genômica/métodos , Adaptação Fisiológica/genética , Sequência de Aminoácidos , Animais , Carnivoridade , Gatos/classificação , Mapeamento Cromossômico , Variações do Número de Cópias de DNA , Cães , Feminino , Deleção de Genes , Duplicação Gênica , Masculino , Proteínas de Membrana Transportadoras/classificação , Proteínas de Membrana Transportadoras/genética , Dados de Sequência Molecular , Filogenia , Seleção Genética/genética , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Especificidade da Espécie
12.
J Arthroplasty ; 31(4): 776-80, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26684270

RESUMO

BACKGROUND: Filtered-exhaust helmet systems are commonplace during total joint arthroplasty, but their ability to limit intraoperative contamination has been questioned. We hypothesized that activation of the airflow system after complete gowning would lead to decreased contamination of the surgical environment. METHODS: Using a fluorescent particle model, the maximal particle spread from a filtered-exhaust helmet and contamination of the surgical environment based on timing of airflow activation through simulated surgical gowning procedures were evaluated. RESULTS: Helmet airflow analysis revealed particle spread greater than 5 feet in all trials. Activation before gowning resulted in a significantly greater contamination in the control group compared with the experimental group (P = .014). CONCLUSIONS: We recommend complete surgical gowning before activation of the airflow system.


Assuntos
Contaminação de Equipamentos , Controle de Infecções/normas , Salas Cirúrgicas/normas , Infecção da Ferida Cirúrgica/prevenção & controle , Dispositivos de Proteção da Cabeça
13.
Nucleic Acids Res ; 40(20): 10375-83, 2012 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-22941652

RESUMO

Marine cyanobacteria of the genus Prochlorococcus represent numerically dominant photoautotrophs residing throughout the euphotic zones in the open oceans and are major contributors to the global carbon cycle. Prochlorococcus has remained a genetically intractable bacterium due to slow growth rates and low transformation efficiencies using standard techniques. Our recent successes in cloning and genetically engineering the AT-rich, 1.1 Mb Mycoplasma mycoides genome in yeast encouraged us to explore similar methods with Prochlorococcus. Prochlorococcus MED4 has an AT-rich genome, with a GC content of 30.8%, similar to that of Saccharomyces cerevisiae (38%), and contains abundant yeast replication origin consensus sites (ACS) evenly distributed around its 1.66 Mb genome. Unlike Mycoplasma cells, which use the UGA codon for tryptophane, Prochlorococcus uses the standard genetic code. Despite this, we observed no toxic effects of several partial and 15 whole Prochlorococcus MED4 genome clones in S. cerevisiae. Sequencing of a Prochlorococcus genome purified from yeast identified 14 single base pair missense mutations, one frameshift, one single base substitution to a stop codon and one dinucleotide transversion compared to the donor genomic DNA. We thus provide evidence of transformation, replication and maintenance of this 1.66 Mb intact bacterial genome in S. cerevisiae.


Assuntos
Genoma Bacteriano , Prochlorococcus/genética , Clonagem Molecular , Genes Bacterianos , Mutação , Origem de Replicação , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Análise de Sequência de DNA
14.
Nat Commun ; 15(1): 5658, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38969634

RESUMO

Understanding and treating human diseases require valid animal models. Leveraging the genetic diversity in rhesus macaque populations across eight primate centers in the United States, we conduct targeted-sequencing on 1845 individuals for 374 genes linked to inherited human retinal and neurodevelopmental diseases. We identify over 47,000 single nucleotide variants, a substantial proportion of which are shared with human populations. By combining rhesus and human allele frequencies with established variant prediction methods, we develop a machine learning-based score that outperforms established methods in predicting missense variant pathogenicity. Remarkably, we find a marked number of loss-of-function variants and putative deleterious variants, which may lead to the development of rhesus disease models. Through phenotyping of macaques carrying a pathogenic OPA1:p.A8S variant, we identify a genetic model of autosomal dominant optic atrophy. Finally, we present a public website housing variant and genotype data from over two thousand rhesus macaques.


Assuntos
Modelos Animais de Doenças , Variação Genética , Macaca mulatta , Animais , Macaca mulatta/genética , Humanos , Frequência do Gene , Atrofia Óptica Autossômica Dominante/genética , Polimorfismo de Nucleotídeo Único , Fenótipo , Aprendizado de Máquina , Genótipo , Mutação de Sentido Incorreto
15.
Am J Biol Anthropol ; 184(3): e24920, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38447005

RESUMO

OBJECTIVES: Interpretations of the primate and human fossil record often rely on the estimation of somatic dimensions from bony measures. Both somatic and skeletal variation have been used to assess how primates respond to environmental change. However, it is unclear how well skeletal variation matches and predicts soft tissue. Here, we empirically test the relationship between tissues by comparing somatic and skeletal measures using paired measures of pre- and post-mortem rhesus macaques from Cayo Santiago, Puerto Rico. MATERIALS AND METHODS: Somatic measurements were matched with skeletal dimensions from 105 rhesus macaque individuals to investigate paired signals of variation (i.e., coefficients of variation, sexual dimorphism) and bivariate codependence (reduced major axis regression) in measures of: (1) limb length; (2) joint breadth; and (3) limb circumference. Predictive models for the estimation of soft tissue dimensions from skeletons were built from Ordinary Least Squares regressions. RESULTS: Somatic and skeletal measurements showed statistically equivalent coefficients of variation and sexual dimorphism as well as high epiphyses-present ordinary least square (OLS) correlations in limb lengths (R2 >0.78, 0.82), joint breadths (R2 >0.74, 0.83) and, to a lesser extent, limb circumference (R2 >0.53, 0.68). CONCLUSION: Skeletal measurements are good substitutions for somatic values based on population signals of variation. OLS regressions indicate that skeletal correlates are highly predictive of somatic dimensions. The protocols and regression equations established here provide a basis for reliable reconstruction of somatic dimension from catarrhine fossils and validate our ability to compare or combine results of studies based on population data of either hard or soft tissue proxies.


Assuntos
Osso e Ossos , Macaca mulatta , Animais , Macaca mulatta/anatomia & histologia , Feminino , Masculino , Porto Rico , Osso e Ossos/anatomia & histologia , Antropologia Física , Caracteres Sexuais , Extremidades/anatomia & histologia
16.
bioRxiv ; 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38260273

RESUMO

Biological relatedness is a key consideration in studies of behavior, population structure, and trait evolution. Except for parent-offspring dyads, pedigrees capture relatedness imperfectly. The number and length of DNA segments that are identical-by-descent (IBD) yield the most precise estimates of relatedness. Here, we leverage novel methods for estimating locus-specific IBD from low coverage whole genome resequencing data to demonstrate the feasibility and value of resolving fine-scaled gradients of relatedness in free-living animals. Using primarily 4-6× coverage data from a rhesus macaque (Macaca mulatta) population with available long-term pedigree data, we show that we can call the number and length of IBD segments across the genome with high accuracy even at 0.5× coverage. The resulting estimates demonstrate substantial variation in genetic relatedness within kin classes, leading to overlapping distributions between kin classes. They identify cryptic genetic relatives that are not represented in the pedigree and reveal elevated recombination rates in females relative to males, which allows us to discriminate maternal and paternal kin using genotype data alone. Our findings represent a breakthrough in the ability to understand the predictors and consequences of genetic relatedness in natural populations, contributing to our understanding of a fundamental component of population structure in the wild.

17.
Geroscience ; 46(2): 2107-2122, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37853187

RESUMO

Increasing age is associated with dysregulated immune function and increased inflammation-patterns that are also observed in individuals exposed to chronic social adversity. Yet we still know little about how social adversity impacts the immune system and how it might promote age-related diseases. Here, we investigated how immune cell diversity varied with age, sex and social adversity (operationalized as low social status) in free-ranging rhesus macaques. We found age-related signatures of immunosenescence, including lower proportions of CD20 + B cells, CD20 + /CD3 + ratio, and CD4 + /CD8 + T cell ratio - all signs of diminished antibody production. Age was associated with higher proportions of CD3 + /CD8 + Cytotoxic T cells, CD16 + /CD3- Natural Killer cells, CD3 + /CD4 + /CD25 + and CD3 + /CD8 + /CD25 + T cells, and CD14 + /CD16 + /HLA-DR + intermediate monocytes, and lower levels of CD14 + /CD16-/HLA-DR + classical monocytes, indicating greater amounts of inflammation and immune dysregulation. We also found a sex-dependent effect of exposure to social adversity (i.e., low social status). High-status males, relative to females, had higher CD20 + /CD3 + ratios and CD16 + /CD3 Natural Killer cell proportions, and lower proportions of CD8 + Cytotoxic T cells. Further, low-status females had higher proportions of cytotoxic T cells than high-status females, while the opposite was observed in males. High-status males had higher CD20 + /CD3 + ratios than low-status males. Together, our study identifies the strong age and sex-dependent effects of social adversity on immune cell proportions in a human-relevant primate model. Thus, these results provide novel insights into the combined effects of demography and social adversity on immunity and their potential contribution to age-related diseases in humans and other animals.


Assuntos
Antígenos HLA-DR , Alienação Social , Masculino , Feminino , Animais , Humanos , Macaca mulatta , Linfócitos T CD8-Positivos , Inflamação
18.
Cell Genom ; 4(7): 100589, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38942023

RESUMO

Humans exhibit sex differences in the prevalence of many neurodevelopmental disorders and neurodegenerative diseases. Here, we generated one of the largest multi-brain-region bulk transcriptional datasets for the rhesus macaque and characterized sex-biased gene expression patterns to investigate the translatability of this species for sex-biased neurological conditions. We identify patterns similar to those in humans, which are associated with overlapping regulatory mechanisms, biological processes, and genes implicated in sex-biased human disorders, including autism. We also show that sex-biased genes exhibit greater genetic variance for expression and more tissue-specific expression patterns, which may facilitate rapid evolution of sex-biased genes. Our findings provide insights into the biological mechanisms underlying sex-biased disease and support the rhesus macaque model for the translational study of these conditions.


Assuntos
Encéfalo , Macaca mulatta , Caracteres Sexuais , Transcriptoma , Animais , Macaca mulatta/genética , Encéfalo/metabolismo , Feminino , Masculino , Humanos , Evolução Molecular
19.
Am J Biol Anthropol ; 184(2): e24901, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38445298

RESUMO

OBJECTIVES: Estimation of body mass from skeletal metrics can reveal important insights into the paleobiology of archeological or fossil remains. The standard approach constructs predictive equations from postcrania, but studies have questioned the reliability of traditional measures. Here, we examine several skeletal features to assess their accuracy in predicting body mass. MATERIALS AND METHODS: Antemortem mass measurements were compared with common skeletal dimensions from the same animals postmortem, using 115 rhesus macaques (male: n = 43; female: n = 72). Individuals were divided into training (n = 58) and test samples (n = 57) to build and assess Ordinary Least Squares or multivariate regressions by residual sum of squares (RSS) and AIC weights. A leave-one-out approach was implemented to formulate the best fit multivariate models, which were compared against a univariate and a previously published catarrhine body-mass estimation model. RESULTS: Femur circumference represented the best univariate model. The best model overall was composed of four variables (femur, tibia and fibula circumference and humerus length). By RSS and AICw, models built from rhesus macaque data (RSS = 26.91, AIC = -20.66) better predicted body mass than did the catarrhine model (RSS = 65.47, AIC = 20.24). CONCLUSION: Body mass in rhesus macaques is best predicted by a 4-variable equation composed of humerus length and hind limb midshaft circumferences. Comparison of models built from the macaque versus the catarrhine data highlight the importance of taxonomic specificity in predicting body mass. This paper provides a valuable dataset of combined somatic and skeletal data in a primate, which can be used to build body mass equations for fragmentary fossil evidence.


Assuntos
Macaca mulatta , Animais , Macaca mulatta/anatomia & histologia , Feminino , Masculino , Antropologia Física/métodos , Peso Corporal , Osso e Ossos/anatomia & histologia , Úmero/anatomia & histologia
20.
Microbiol Spectr ; : e0297423, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37750731

RESUMO

While skin microbes are known to mediate human health and disease, there has been minimal research on the interactions between skin microbiota, social behavior, and year-to-year effects in non-human primates-important animal models for translational biomedical research. To examine these relationships, we analyzed skin microbes from 78 rhesus macaques living on Cayo Santiago Island, Puerto Rico. We considered age, sex, and social group membership, and characterized social behavior by assessing dominance rank and patterns of grooming as compared to nonsocial behaviors. To measure the effects of a shifting environment, we sampled skin microbiota (based on sequence analysis of the 16S rRNA V4 region) and assessed weather across sampling periods between 2013 and 2015. We hypothesized that, first, monkeys with similar social behavior and/or in the same social group would possess similar skin microbial composition due, in part, to physical contact, and, second, microbial diversity would differ across sampling periods. We found significant phylum-level differences between social groups in the core microbiome as well as an association between total grooming rates and alpha diversity in the complete microbiome, but no association between microbial diversity and measures of rank or other nonsocial behaviors. We also identified alpha and beta diversity differences in microbiota and differential taxa abundance across two sampling periods. Our findings indicate that social dynamics interact with yearly environmental changes to shape the skin microbiota in rhesus macaques, with potential implications for understanding the factors affecting the microbiome in humans, which share many biological and social characteristics with these animals. IMPORTANCE Primate studies are valuable for translational and evolutionary insights into the human microbiome. The majority of primate microbiome studies focus on the gut, so less is known about the factors impacting the microbes on skin and how their links affect health and behavior. Here, we probe the impact of social interactions and the yearly environmental changes on food-provisioned, free-ranging monkeys living on a small island. We expected animals that lived together and groomed each other would have more similar microbes on their skin, but surprisingly found that the external environment was a stronger influence on skin microbiome composition. These findings have implications for our understanding of the human skin microbiome, including potential manipulations to improve health and treat disease.

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