New World Monkeys Research Articles

The bifidobacterial distribution in the microbiome of captive primates reflects parvorder and feed specialization of the host

Bifidobacteria, which commonly inhabit the primate gut, are beneficial contributors to host wellbeing. Anatomical differences and natural habitat allow an arrangement of primates into two main parvorders; New World monkeys (NWM) and Old World monkeys (OWM). The number of newly described bifidobacterial species is clearly elevated in NWM. This corresponds to our finding that bifidobacteria were the dominant group of cultivated gut anaerobes in NWM, while their numbers halved in OWM and were often replaced by Clostridiaceae with sarcina morphology. We examined an extended MALDI-TOF MS database as a potential identification tool for rapid screening of bifidobacterial distribution in captive primates. Bifidobacterial isolates of NWM were assigned mainly to species of primate origin, while OWM possessed typically multi-host bifidobacteria. Moreover, bifidobacterial counts reflected the feed specialization of captive primates decreasing from frugivore-insectivores, gummivore-insectivores, frugivore-folivores to frugivore-omnivores. Amplicon sequencing analysis supported this trend with regards to the inverse ratio of Actinobacteria and Firmicutes. In addition, a significantly higher diversity of the bacterial population in OWM was found. The evolution specialization of primates seems to be responsible for Bifidobacterium abundance and species occurrence. Balanced microbiota of captive primates could be supported by optimized prebiotic and probiotic stimulation based on the primate host.

The Stabilizing Function of the Tail During Arboreal Quadrupedalism.

Locomotion on the narrow and compliant supports of the arboreal environment is inherently precarious. Previous studies have identified a host of morphological and behavioral specializations in arboreal animals broadly thought to promote stability when on precarious substrates. Less well-studied is the role of the tail in maintaining balance. However, prior anatomical studies have found that arboreal taxa frequently have longer tails for their body size than their terrestrial counterparts, and prior laboratory studies of tail kinematics and the effects of tail reduction in focal taxa have broadly supported the hypothesis that the tail is functionally important for maintaining balance on narrow and mobile substrates. In this set of studies, we extend this work in two ways. First, we used a laboratory dataset on three-dimensional segmental kinematics and tail inertial properties in squirrel monkeys (Saimiri boliviensis) to investigate how tail angular momentum is modulated during steady-state locomotion on narrow supports. In the second study, we used a quantitative dataset on quadrupedal locomotion in wild platyrrhine monkeys to investigate how free-ranging arboreal animals adjust tail movements in response to substrate variation, focusing on kinematic measures validated in prior laboratory studies of tail mechanics (including the laboratory data presented). Our laboratory results show that S. boliviensis significantly increase average tail angular momentum magnitudes and amplitudes on narrow supports, and primarily regulate that momentum by adjusting the linear and angular velocity of the tail (rather than via changes in tail posture per se). We build on these findings in our second study by showing that wild platyrrhines responded to the precarity of narrow and mobile substrates by extending the tail and exaggerating tail displacements, providing ecological validity to the laboratory studies of tail mechanics presented here and elsewhere. In conclusion, our data support the hypothesis that the long and mobile tails of arboreal animals serve a biological role of enhancing stability when moving quadrupedally over narrow and mobile substrates. Tail angular momentum could be used to cancel out the angular momentum generated by other parts of the body during steady-state locomotion, thereby reducing whole-body angular momentum and promoting stability, and could also be used to mitigate the effects of destabilizing torques about the support should the animals encounter large, unexpected perturbations. Overall, these studies suggest that long and mobile tails should be considered among the fundamental suite of adaptations promoting safe and efficient arboreal locomotion.

Vertical clinging and leaping induced evolutionary rate shifts in postcranial evolution of tamarins and marmosets (Primates, Callitrichidae)

BackgroundCallitrichids comprise a diverse group of platyrrhine monkeys that are present across South and Central America. Their secondarily evolved small size and pointed claws allow them to cling to vertical trunks of a large diameter. Within callitrichids, lineages with a high affinity for vertical supports often engage in trunk-to-trunk leaping. This vertical clinging and leaping (VCL) differs from horizontal leaping (HL) in terms of the functional demands imposed on the musculoskeletal system, all the more so as HL often occurs on small compliant terminal branches. We used quantified shape descriptors (3D geometric morphometrics) and phylogenetically-informed analyses to investigate the evolution of the shape and size of the humerus and femur, and how this variation reflects locomotor behavior within Callitrichidae.ResultsThe humerus of VCL-associated species has a narrower trochlea compared with HL species. It is hypothesized that this contributes to greater elbow mobility. The wider trochlea in HL species appears to correspondingly provide greater stability to the elbow joint. The femur in VCL species has a smaller head and laterally-oriented distal condyles, possibly to reduce stresses during clinging. Similarly, the expanded lesser trochanters visible in VCL species provide a greater lever for the leg retractors and are thus also interpreted as an adaptation to clinging. Evolutionary rate shifts to faster shape and size changes of humerus and femur occurred in the Leontocebus clade when a shift to slower rates occurred in the Saguinus clade.ConclusionsBased on the study of evolutionary rate shifts, the transition to VCL behavior within callitrichids (specifically the Leontocebus clade) appears to have been an opportunity for radiation, rather than a specialization that imposed constraints on morphological diversity. The study of the evolution of callitrichids suffers from a lack of comparative analyses of limb mechanics during trunk-to-trunk leaping, and future work in this direction would be of great interest.

The expression of type I and II gonadotropin-releasing hormone receptors transcripts in Vervet monkey (Chlorocebus aethiops) spermatozoa

Gonadotropin-Releasing Hormone (GnRH), acting via the GnRH receptor (GnRHR), and a member of G-protein coupled receptor (GPCR), plays an essential role in the control of reproduction while operating primarily at the hypothalamic level of the gonadotropic axis. GnRH and its receptor are co-expressed in certain specific cells, suggesting an autocrine regulation of such cells. In the male reproductive system, two forms of GnRH (I and II) and its receptors (GnRHR) are present in the human and non-human primate (NHP) testis, prostate, epididymis, seminal vesicle, and human spermatozoa. In humans, the GnRHR-II receptor gene is disrupted by a frameshift in exon 1 and a stop codon in exon 2, rendering the receptor non-functional, whereas a fully functional GnRHR-II receptor is present in New-World and Old-World monkeys. There is no evidence of the existence of a GnRH receptor in NHP sperm. Since the NHP has a phylogenetic relationship to man and is often used as models in reproductive physiology, this present study aimed to determine GnRHR-I and GnRHR-II in Vervet monkey (Chlorocebus aethiops) spermatozoa. A total of 24 semen samples were obtained from four adult Vervet monkeys through electro-ejaculation and utilized for genotyping and gene expression analysis of GnRHR-I and II. Here we report that both receptors were successfully identified in the Vervet monkey sperm with the abundance of GnRHR-I gene expression compared to GnRHR-II. In comparison to the human, there is no evidence of such a stop codon at position 179 in exon 2 of the Vervet GnRHR-II. These findings suggest that both receptors are transcriptionally functional in Vervet spermatozoa.

Plasmodium simium: Population Genomics Reveals the Origin of a Reverse Zoonosis.

The population history of Plasmodium simium, which causes malaria in sylvatic Neotropical monkeys and humans along the Atlantic Coast of Brazil, remains disputed. Genetically diverse P vivax populations from various sources, including the lineages that founded the species P simium, are thought to have arrived in the Americas in separate migratory waves. We use population genomic approaches to investigate the origin and evolution of P simium. We find a minimal genome-level differentiation between P simium and present-day New World P vivax isolates, consistent with their common geographic origin and subsequent divergence on this continent. The meagre genetic diversity in P simium samples from humans and monkeys implies a recent transfer from humans to non-human primates - a unique example of malaria as a reverse zoonosis of public health significance. Likely genomic signatures of P simium adaptation to new hosts include the deletion of >40% of a key erythrocyte invasion ligand, PvRBP2a, which may have favored more efficient simian host cell infection. New World P vivax lineages that switched from humans to platyrrhine monkeys founded the P simium population that infects nonhuman primates and feeds sustained human malaria transmission in the outskirts of major cities.

Identifying Primate ACE2 Variants That Confer Resistance to SARS-CoV-2.

SARS-CoV-2 infects humans through the binding of viral S-protein (spike protein) to human angiotensin I converting enzyme 2 (ACE2). The structure of the ACE2-S-protein complex has been deciphered and we focused on the 27 ACE2 residues that bind to S-protein. From human sequence databases, we identified nine ACE2 variants at ACE2–S-protein binding sites. We used both experimental assays and protein structure analysis to evaluate the effect of each variant on the binding affinity of ACE2 to S-protein. We found one variant causing complete binding disruption, two and three variants, respectively, strongly and mildly reducing the binding affinity, and two variants strongly enhancing the binding affinity. We then collected the ACE2 gene sequences from 57 nonhuman primates. Among the 6 apes and 20 Old World monkeys (OWMs) studied, we found no new variants. In contrast, all 11 New World monkeys (NWMs) studied share four variants each causing a strong reduction in binding affinity, the Philippine tarsier also possesses three such variants, and 18 of the 19 prosimian species studied share one variant causing a strong reduction in binding affinity. Moreover, one OWM and three prosimian variants increased binding affinity by >50%. Based on these findings, we proposed that the common ancestor of primates was strongly resistant to and that of NWMs was completely resistant to SARS-CoV-2 and so is the Philippine tarsier, whereas apes and OWMs, like most humans, are susceptible. This study increases our understanding of the differences in susceptibility to SARS-CoV-2 infection among primates.

The lymphatic system as a potential mechanism of spread of melioidosis following ingestion of Burkholderia pseudomallei.

Burkholderia pseudomallei is the causative agent of melioidosis, which is a Gram negative, facultative intracellular bacterium. Disease is prevalent in SE Asia and in northern Australia, as well as in other tropical and subtropical regions. Recently, there is an increasing awareness of the importance of bacterial ingestion as a potential route of infection, particularly in cases of unexplained origin of the disease. The marmoset is a New World Monkey (NWM) species that is being developed as an alternative NHP model to complement the more traditionally used Old World Monkeys (OWM). Models have been developed for the traditional routes of disease acquisition, subcutaneous and inhalational. This manuscript details the development and characterisation of an ingestion model of melioidosis. Dose-ranging study assessed the lethality of B. pseudomallei and disease progression was assessed by euthanizing animals at predetermined time points, 12, 36, 48 and 54 hours post-challenge. Challenge doses of greater than 6.2 x 106 cfu resulted in an acute, lethal, febrile disease. Following challenge the lung was the first organ, outside of the gastrointestinal tract, to become colonised. Enteritis (duodenitis, ileitis and/or jejunitis) was observed in sections of the small intestine from animals that succumbed to disease. However, the most severe pathological features were observed in the mesenteric lymph nodes from these animals. These findings are consistent with lymphatic draining as route of dissemination.

Evolution of HLA-F and its orthologues in primate species: a complex tale of conservation, diversification and inactivation

HLA-F represents one of the nonclassical MHC class I molecules in humans. Its main characteristics involve low levels of polymorphism in combination with a restricted tissue distribution. This signals that the gene product executes a specialised function, which, however, is still poorly understood. Relatively little is known about the evolutionary equivalents of this gene in nonhuman primates, especially with regard to population data. Here we report a comparative genetic analysis of the orthologous genes of HLA-F in various great ape, Old World monkey (OWM), and New World monkey (NWM) species. HLA-F-related transcripts were found in all subjects studied. Low levels of polymorphism were encountered, although the length of the predicted gene products may vary. In most species, one or two transcripts were discovered, indicating the presence of only one active F-like gene per chromosome. An exception was provided by a New World monkey species, namely, the common marmoset. In this species, the gene has been subject to duplication, giving rise to up to six F-like transcripts per animal. In humans, great apes, and OWM, and probably the majority of the NWM species, the evolutionary equivalents of the HLA-F gene experienced purifying selection. In the marmoset, however, the gene was initially duplicated, but the expansion was subjected afterwards to various mechanisms of genetic inactivation, as evidenced by the presence of pseudogenes and an array of genetic artefacts in a section of the transcripts.

Validation of a method for quantifying urinary C-peptide in platyrrhine monkeys

Urinary C-peptide (UCP) is a biomarker for insulin that can be used as a non-invasive physiological measure of energy balance. Previous research has validated the use of UCP to quantify energy balance in catarrhines; however, there have been no such studies in platyrrhines. Validation is necessary in this lineage of primates as divergent evolution has resulted in varied organization of insulin genes. Here, we evaluate a method for quantifying UCP in platyrrhines to measure energetic expenditure, a key component of calculating energy balance. Urine samples were opportunistically collected from laboratory-housed tufted capuchins (Sapajus apella) during exercise activities. To examine the efficacy of using UCP as a means for assessing energetic condition, we analyzed urine samples collected before and after exercise. Urinary C-peptide concentrations were measured using a commercial C-peptide radioimmunoassay. We found that on average, UCP concentrations were 0.34 ng/mL lower after exercise than they were prior to exercise (range =0.04 to 0.71 ng/mL). The rateofenergy expenditureper unit time was greater when capuchins were exercising at faster speeds. Concordantly, UCP concentrations decreased more following exercise at those faster speeds. Parallelism of serial dilutions of samples was calculated to assess the precision of UCP concentrations produced using these methods. Measured UCP concentrations decreased at expected intervals in accordance with each dilution factor. Our results provide biological validation of the use of a commercial assay for quantifying UCP as a measure of energy expenditure in this platyrrhine species.

Genetic variability of the sws1 cone opsin gene among New World monkeys.

Vision is a major sense for Primates and the ability to perceive colors has great importance for the species ecology and behavior. Visual processing begins with the activation of the visual opsins in the retina, and the spectral absorption peaks are highly variable among species. In most Primates, LWS/MWS opsins are responsible for sensitivity to long/middle wavelengths within the visible light spectrum, and SWS1 opsins provide sensitivity to short wavelengths, in the violet region of the spectrum. In this study, we aimed to investigate the genetic variation on the sws1 opsin gene of New World monkeys (NWM) and search for amino acid substitutions that might be associated with the different color vision phenotypes described for a few species. We sequenced the exon 1 of the sws1 opsin gene of seven species from the families Callitrichidae, Cebidae, and Atelidae, and searched for variation at the spectral tuning sites 46, 49, 52, 86, 90, 93, 114, 116, and 118. Among the known spectral tuning sites, only residue 114 was variable. To investigate whether other residues have a functional role in the SWS1 absorption peak, we performed computational modeling of wild-type SWS1 and mutants A50I and A50V, found naturally among the species investigated. Although in silico analysis did not show any visible effect caused by these substitutions, it is possible that interactions of residue 50 with other sites might have some effect in the spectral shifts in the order of ~14 nm, found among the NWM. We also performed phylogenetic reconstruction of the sws1 gene, which partially recovered the species phylogeny. Further studies will be important to uncover the mutations responsible for the phenotypic variability of the SWS1 of NWM, and how spectral tuning may be associated with specific ecological features such as preferred food items and habitat use.

NEW WORLD MONKEYS AS MODELS FOR TESTING TRIPLE-KNOCKOUT (TKO) PIG RED BLOOD CELL OR SKIN TRANSPLANTS

Background: TKO pigs are an optimal source of organs for transplantation into human recipients, who do not commonly have high levels of preformed antibodies against TKO pig cells. However, Old World monkeys (OWMs), e.g., baboons, do have antibodies directed to TKO pig cells, associated with significant serum cytotoxicity. New World monkeys (NWMs), e.g., capuchins, have low or no antibodies to TKO pig cells. Our aims were (i) to measure anti-pig IgM/IgG binding and (ii) complement-dependent cytotoxicity (CDC) to GTKO and TKO pig cells using sera from humans, baboons, and capuchins, and (iii) to measure the efficacy of anti-thymocyte globulin (ATG) and Rituximab in these three species. Methods: (i) Sera from humans (n=9), baboons (n=6), and capuchins (n=9) were tested by flow cytometry for binding of IgM and IgG to peripheral blood mononuclear cells (PBMCs) from GTKO and TKO pigs. Binding intensity was presented as relative geometric mean (rGM). (ii) The sera (final concentration 25%) were also tested for CDC to the same pig cells by flow cytometry. (iii) The effect of ATG and Rituximab on human (n=2), baboon (n=2), and capuchin (n=3) PBMCs or B cells deletion was measured by flow cytometry. Results: Binding of serum IgM/IgG to pig cells (Figure1) Mean serum anti-GTKO IgM and IgG binding were both significantly lower in baboons than in humans and capuchins (p<0.01). Mean baboon anti-TKO IgM binding was significantly higher than in humans and capuchins (p<0.01). Mean capuchin anti-TKO IgG was significantly lower than in humans and baboons (p<0.01). Serum CDC to pig cells (Figure1) Mean serum CDC of GTKO PBMCs did not differ between the three species. Baboon serum CDC of TKO PBMCs was significantly greater than in humans and capuchins (p<0.01), but there was no difference between humans and capuchins. The CDC of ATG and Rituximab on PBMCs and B cells (Figure2) ATG (25-50µg/ml) depleted fewer PBMCs in capuchins and baboons than in humans, but the depletion in capuchins was not significantly different from that in baboons, except at high concentration (100µg/ml). In contrast, the effect of Rituximab in depleting B cells in capuchins was very limited, and significantly less than in humans and baboons (p<0.05 or 0.01). Conclusions: When TKO pig organs are transplanted, OWMs, e.g., baboons, would be less than ideal as recipients as they do not mimic the human immune response. NWMs, e.g., capuchins, are to be preferred. However, their small size and the reduced effect of ATG, and, particularly, Rituximab, limit their use as recipients of organs, though they would be ideal for studies of TKO pig red blood cell transfusion or skin transplantation, where immunosuppressive therapy is not required.Work on xenotransplantation at the University of Alabama at Birmingham is supported in part by NIH NIAID U19 grant AI090959 and in part by a grant to UAB from United Therapeutics.

Detection of Toxoplasma gondii DNA in heart tissue from common marmoset (Callithrix jacchus) monitored for yellow fever and rabies in Pernambuco state, Northeastern of Brazil.

There is limited available information concerning the prevalence of Toxoplasma gondii in noncaptive monkeys. Also, New World monkeys (NWM) are highly susceptible to toxoplasmosis, which is a conservation concern. This study aimed to investigate apicomplexan parasites in common marmosets (Callithrix jacchus) collected for yellow fever and rabies surveillance program in Northeastern region of Brazil. Heart fragments of 39 free-ranging common marmosets were analyzed for the presence of the 18S rDNA gene of apicomplexan parasites by nested PCR. Positive samples were sequenced. T. gondii DNA was detected in 17.9% (7/39) of the analyzed animals. This study is the first report on T. gondii in Callithrix jacchus in Brazil. These findings should be an alert for wildlife conservation institutions, as high susceptibility and mortality were reported for captive NWM.

Human Natural Antibodies to Mammalian Carbohydrate Antigens as Unsung Heroes Protecting against Past, Present, and Future Viral Infections.

Human natural antibodies to mammalian carbohydrate antigens (MCA) bind to carbohydrate-antigens synthesized in other mammalian species and protect against zoonotic virus infections. Three such anti-MCA antibodies are: (1) anti-Gal, also produced in Old-World monkeys and apes, binds to α-gal epitopes synthesized in non-primate mammals, lemurs, and New-World monkeys; (2) anti-Neu5Gc binds to Neu5Gc (N-glycolyl-neuraminic acid) synthesized in apes, Old-World monkeys, and many non-primate mammals; and (3) anti-Forssman binds to Forssman-antigen synthesized in various mammals. Anti-viral protection by anti-MCA antibodies is feasible because carbohydrate chains of virus envelopes are synthesized by host glycosylation machinery and thus are similar to those of their mammalian hosts. Analysis of MCA glycosyltransferase genes suggests that anti-Gal appeared in ancestral Old-World primates following catastrophic selection processes in which parental populations synthesizing α-gal epitopes were eliminated in enveloped virus epidemics. However, few mutated offspring in which the α1,3galactosyltransferase gene was accidentally inactivated produced natural anti-Gal that destroyed viruses presenting α-gal epitopes, thereby preventing extinction of mutated offspring. Similarly, few mutated hominin offspring that ceased to synthesize Neu5Gc produced anti-Neu5Gc, which destroyed viruses presenting Neu5Gc synthesized in parental hominin populations. A present-day example for few humans having mutations that prevent synthesis of a common carbohydrate antigen (produced in >99.99% of humans) is blood-group Bombay individuals with mutations inactivating H-transferase; thus, they cannot synthesize blood-group O (H-antigen) but produce anti-H antibody. Anti-MCA antibodies prevented past extinctions mediated by enveloped virus epidemics, presently protect against zoonotic-viruses, and may protect in future epidemics. Travelers to regions with endemic zoonotic viruses may benefit from vaccinations elevating protective anti-MCA antibody titers.

Old World Monkeys are less than ideal transplantation models for testing pig organs lacking three carbohydrate antigens (Triple-Knockout)

Triple-knockout (TKO) pigs (with added protective human transgenes) are likely to be optimal sources of organs for clinical organ xenotransplantation because many humans have minimal or no natural antibody to TKO pig cells. However, Old World monkeys (OWMs) have naturally-existing antibodies directed to TKO cells. We measured anti-pig IgM/IgG binding, and complement-dependent cytotoxicity to wild-type (WT), α1,3-galactosyltransferase gene-knockout (GTKO), and TKO pig peripheral blood mononuclear cells (PBMCs) using sera from humans, several OWMs, and two New World monkeys (NWMs). Furthermore, we compared survival of GTKO (n = 5) and TKO (n = 3) pig kidneys in baboons. OWMs had significantly greater IgM binding and cytotoxicity to TKO PBMCs than humans or NWMs. Mean anti-TKO IgM was significantly higher in OWMs and significantly lower in NWMs than in humans. Cytotoxicity of OWM sera to TKO PBMCs was significantly greater than of human serum, but there was no significant difference between human and NWM sera. The median survival of TKO pig kidneys (4 days) in baboons was significantly shorter than that of GTKO kidneys (136 days) (p < 0.05). Even though considered ideal for clinical xenotransplantation, the presence of naturally-existing antibodies to TKO pig cells in OWMs complicates the transplantation of TKO pig kidneys in OWMs.

A parapithecid stem anthropoid of African origin in the Paleogene of South America.

Phylogenetic evidence suggests that platyrrhine (or New World) monkeys and caviomorph rodents of the Western Hemisphere derive from source groups from the Eocene of Afro-Arabia, a landmass that was ~1500 to 2000 kilometers east of South America during the late Paleogene. Here, we report evidence for a third mammalian lineage of African origin in the Paleogene of South America-a newly discovered genus and species of parapithecid anthropoid primate from Santa Rosa in Amazonian Perú. Bayesian clock-based phylogenetic analysis nests this genus (Ucayalipithecus) deep within the otherwise Afro-Arabian clade Parapithecoidea and indicates that transatlantic rafting of the lineage leading to Ucayalipithecus likely took place between ~35 and ~32 million years ago, a dispersal window that includes the major worldwide drop in sea level that occurred near the Eocene-Oligocene boundary.

A South American anthropoid

Paleontology Although there are many primate lineages in the Old World, it is thought that the New World is home to just one group, the platyrrhine monkeys, which appear to have colonized the region during the Eocene. Seiffert et al. describe a new primate species on the basis of fossil molars found in the Peruvian Amazon that appears to belong to the Parapithecidae, a group of stem anthropoid primates best known from northern Africa (see the Perspective by Godinot). The fossils appear to be from a well-differentiated lineage, suggesting that this species had been evolving within South America for some time. It is likely that the ancestors of this new species arrived via a transatlantic rafting event when sea levels dropped at the Eocene–Oligocene transition ∼32 to 35 million years ago. Science , this issue p. [194][1]; see also p. [136][2] [1]: /lookup/doi/10.1126/science.aba1135 [2]: /lookup/doi/10.1126/science.abb4107

Human PZP and common marmoset A2ML1 as pregnancy related proteins

While pregnancy-related proteins (PRP) are known to contribute to immunotolerance during pregnancy, their significance to development of invasive placenta is unclear. We compared PRP expression in humans and the common marmoset (Callithrix jacchus), a new-world monkey. Invasive placenta was observed at the maternal-foetal interface of marmoset placenta from green fluorescent protein (GFP)-expressing foetus and wild type mother. The pregnancy zone protein (PZP) and alpha-2 macroglobulin-like 1 (A2ML1) proteins exhibited the most prominent increase in expression during the second trimester in humans and marmoset, respectively. In humans, PZP accumulated at the maternal-foetal interface and A2ML1 accumulated in the amnion. Similarly, A2ML1 mRNA was detected in marmoset placenta. These proteins belong to the A2M family of protease inhibitors, and both PZP and A2ML1 share around 90% homology between human and marmoset and have highly conserved structures. However, the protease-reacting bait regions of the proteins had lower homology (56.8–60.7% in proteins) relative to the rest of the sequence. Notably, the cleavage site of a proinflammatory proline-endopeptidase was preserved in human PZP and marmoset A2ML1. These proteins contain multiple sites that are cleaved by proteases involving proline-endopeptidase. Systemic regulation of these A2M family proteins may be important in animals with invasive placenta.

Comparison of the pharmacologic profiles of arginine vasopressin and oxytocin analogs at marmoset, titi monkey, macaque, and human oxytocin receptors

The oxytocin-arginine vasopressin (OT-AVP) ligand-receptor family influences a variety of physiological, behavioral, and social behavioral processes in the brain and periphery. The OT-AVP family is highly conserved in mammals, but recent discoveries have revealed remarkable diversity in OT ligands and receptors in New World Monkeys (NWMs) providing a unique opportunity to assess the effects of genetic variation on pharmacological signatures of peptide ligands. The consensus mammalian OT sequence has leucine in the 8th position (Leu8-OT), whereas a number of NWMs, including the marmoset, have proline in the 8th position (Pro8-OT) resulting in a more rigid tail structure. OT and AVP bind to OT’s cognate G-protein coupled receptor (OTR), which couples to various G-proteins (Gi/o, Gq, Gs) to stimulate diverse signaling pathways. CHO cells expressing marmoset (mOTR), titi monkey (tOTR), macaque (qOTR), or human (hOTR) OT receptors were used to compare AVP and OT analog-induced signaling. Assessment of Gq-mediated increase in intracellular calcium (Ca2+) demonstrated that AVP was less potent than OT analogs at OTRs from species whose endogenous ligand is Leu8-OT (tOTR, qOTR, hOTR), relative to Pro8-OT. Likewise, AVP-induced membrane hyperpolarization was less potent at these same OTRs. Evaluation of (Ca2+)-activated potassium (K+) channels using the inhibitors apamin, paxilline, and TRAM-34 demonstrated that both intermediate and large conductance Ca2+-activated K+ channels contributed to membrane hyperpolarization, with different pharmacological profiles identified for distinct ligand-receptor combinations. Understanding more fully the contributions of structure activity relationships for these peptide ligands at vasopressin and OT receptors will help guide the development of OT-mediated therapeutics.

Sensitivity of the polyDetect computational pipeline for phylogenetic analyses

Alu elements are powerful phylogenetic markers. The combination of a recently-developed computational pipeline, polyDetect, with high copy number Alu insertions has previously been utilized to help resolve the Papio baboon phylogeny with high statistical support. Here, the polyDetect method was applied to the highly contentious Cebidae phylogeny within New World monkeys (NWM). The polyDetect method relies on conserved homology/identity of short read sequence data among the species being compared to accurately map predicted shared Alu insertions to each unique flanking sequence. The results of this comprehensive assessment indicate that there were insufficient sequence homology/identity stretches in non-repeated DNA sequences among the four Cebidae genera analyzed in this study to make this strategy phylogenetically viable. The ~20 million years of evolutionary divergence of the Cebidae genera has resulted in random sequence decay within the short read data, obscuring potentially orthologous elements in the species tested. These analyses suggest that the polyDetect pipeline is best suited to resolving phylogenies of more recently diverged lineages when high-quality assembled genomes are not available for the taxa of interest.

NHP-immunome: A translational research-oriented database of non-human primate immune system proteins

We are currently living the advent of a new age for medicine in which basic research is being quickly translated into marketable drugs, and the widespread access to genomics data is allowing the design and implementation of personalized solutions to medical conditions. Non-human primates (NHP) have gained an essential role in drug discovery and safety testing due to their close phylogenetic relationship to humans. In this study, a collection of well characterized genes of the human immune system was used to define the orthology-based immunome in four NHP species, with carefully curated annotations available based on multi-tissue RNA-seq datasets. A broad variation in the frequency of expressed protein isoforms was observed between species. Finally, this analysis also revealed the lack of expression of at least four different chemokines in new-world primates. In addition, transcripts corresponding to four genes including interleukin 12 subunit alpha were expressed in humans but no other primate species analyzed. Access to the non-human primate immunome is available in http://www.fidic.org.co:90/proyecto/.