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Homologous recombination has been extensively studied in humans and a handful of model organisms. Much less is known about recombination in other species, including nonhuman primates. Here, we present a study of crossovers (COs) and noncrossover (NCO) recombination in olive baboons (Papio anubis) from two pedigrees containing a total of 20 paternal and 17 maternal meioses, and compare these results to linkage disequilibrium (LD) based recombination estimates from 36 unrelated olive baboons. We demonstrate how COs, combined with LD-based recombination estimates, can be used to identify genome assembly errors. We also quantify sex-specific differences in recombination rates, including elevated male CO and reduced female CO rates near telomeres. Finally, we add to the increasing body of evidence suggesting that while most NCO recombination tracts in mammals are short (e.g., 1 kb) NCO tracts. For NCO tracts shorter than 10 kb, we fit a mixture of two (truncated) geometric distributions model to the NCO tract length distribution and estimate that >99% of all NCO tracts are very short (mean 24 bp), but the remaining tracts can be quite long (mean 4.3 kb). A single geometric distribution model for NCO tract lengths is incompatible with the data, suggesting that LD-based methods for estimating NCO recombination rates that make this assumption may need to be modified.

AbstractHomologous recombination has been extensively studied in humans and a handful of model organisms. Much less is known about recombination in other species, including non-human primates. Here we present a study of crossovers and non-crossover (NCO) recombination in olive baboons (Papio anubis) from two pedigrees containing a total of 20 paternal and 17 maternal meioses, and compare these results to linkage-disequlibrium (LD) based recombination estimates from 36 unrelated olive baboons. We demonstrate how crossovers, combined with LD-based recombination estimates, can be used to identify genome assembly errors. We also quantify sex-specific differences in recombination rates, including elevated male crossover and reduced female crossover rates near telomeres. Finally, we add to the increasing body of evidence suggesting that while most NCO recombination tracts in mammals are short (e.g., < 500 bp), there are a non-negligible fraction of longer (e.g., > 1 Kb) NCO tracts. We fit a mixture-of-two-geometric distributions model to the NCO tract length distribution and estimate that >99% of all NCO tracts are very short (mean 24 bp), but the remaining tracts can be quite long (mean 11 Kb). A single geometric distribution model for NCO tract lengths is incompatible with the data, suggesting that LD-based methods for estimating NCO recombination rates that make this assumption may need to be modified.SignificanceMost homologous recombination events are noncrossovers (NCO), but little is known about NCO conversion tract lengths. Here we utilize whole-genome sequence data from large baboon pedigrees to estimate the NCO tract length distribution and to study other aspects of recombination.

BackgroundBaboons are a widely used nonhuman primate model for biomedical, evolutionary, and basic genetics research. Despite this importance, the genomic resources for baboons are limited. In particular, the current baboon reference genome Panu_3.0 is a highly fragmented, reference-guided (i.e., not fully de novo) assembly, and its poor quality inhibits our ability to conduct downstream genomic analyses.FindingsHere we present a de novo genome assembly of the olive baboon (Papio anubis) that uses data from several recently developed single-molecule technologies. Our assembly, Panubis1.0, has an N50 contig size of ∼1.46 Mb (as opposed to 139 kb for Panu_3.0) and has single scaffolds that span each of the 20 autosomes and the X chromosome.ConclusionsWe highlight multiple lines of evidence (including Bionano Genomics data, pedigree linkage information, and linkage disequilibrium data) suggesting that there are several large assembly errors in Panu_3.0, which have been corrected in Panubis1.0.

In humans, most germline mutations are inherited from the father. This observation has been widely interpreted as reflecting the replication errors that accrue during spermatogenesis. If so, the male bias in mutation should be substantially lower in a closely related species with similar rates of spermatogonial stem cell divisions but a shorter mean age of reproduction. To test this hypothesis, we resequenced two 3-4 generation nuclear families (totaling 29 individuals) of olive baboons (Papio anubis), who reproduce at approximately 10 years of age on average, and analyzed the data in parallel with three 3-generation human pedigrees (26 individuals). We estimated a mutation rate per generation in baboons of 0.57×10-8 per base pair, approximately half that of humans. Strikingly, however, the degree of male bias in germline mutations is approximately 4:1, similar to that of humans-indeed, a similar male bias is seen across mammals that reproduce months, years, or decades after birth. These results mirror the finding in humans that the male mutation bias is stable with parental ages and cast further doubt on the assumption that germline mutations track cell divisions. Our mutation rate estimates for baboons raise a further puzzle, suggesting a divergence time between apes and Old World monkeys of 65 million years, too old to be consistent with the fossil record; reconciling them now requires not only a slowdown of the mutation rate per generation in humans but also in baboons.

ABSTRACT: Besides macaques, baboons are the most commonly used nonhuman primate in biomedical research. Despite this importance, the genomic resources for baboons are quite limited. In particular, the current baboon reference genome Panu_3.0 is a highly fragmented, reference-guided (i.e., not fully de novo) assembly, and its poor quality inhibits our ability to conduct downstream genomic analyses. Here we present a truly de novo genome assembly of the olive baboon (Papio anubis) that uses data from several recently developed single-molecule technologies. Our assembly, Panubis1.0, has an N50 contig size of ~1.46 Mb (as opposed to 139 Kb for Panu_3.0), and has single scaffolds that span each of the 20 autosomes and the X chromosome. We highlight multiple lines of evidence (including Bionano Genomics data, pedigree linkage information, and linkage disequilibrium data) suggesting that there are several large assembly errors in Panu_3.0, which have been corrected in Panubis1.0.

Baboons (genus Papio) are broadly studied in the wild and in captivity. They are widely used as a nonhuman primate model for biomedical studies, and the Southwest National Primate Research Center (SNPRC) at Texas Biomedical Research Institute has maintained a large captive baboon colony for more than 50 yr. Unlike other model organisms, however, the genomic resources for baboons are severely lacking. This has hindered the progress of studies using baboons as a model for basic biology or human disease. Here, we describe a data set of 100 high-coverage whole-genome sequences obtained from the mixed colony of olive (P. anubis) and yellow (P. cynocephalus) baboons housed at the SNPRC. These data provide a comprehensive catalog of common genetic variation in baboons, as well as a fine-scale genetic map. We show how the data can be used to learn about ancestry and admixture and to correct errors in the colony records. Finally, we investigated the consequences of inbreeding within the SNPRC colony and found clear evidence for increased rates of infant mortality and increased homozygosity of putatively deleterious alleles in inbred individuals.

Baboons (genus Papio) are broadly studied in the wild and in captivity. They are widely used as a nonhuman primate model for biomedical studies, and the Southwest National Primate Research Center (SNPRC) at Texas Biomedical Research Institute has maintained a large captive baboon colony for more than 50 yr. Unlike other model organisms, however, the genomic resources for baboons are severely lacking. This has hindered the progress of studies using baboons as a model for basic biology or human disease. Here, we describe a data set of 100 high-coverage whole-genome sequences obtained from the mixed colony of olive (P. anubis) and yellow (P. cynocephalus) baboons housed at the SNPRC. These data provide a comprehensive catalog of common genetic variation in baboons, as well as a fine-scale genetic map. We show how the data can be used to learn about ancestry and admixture and to correct errors in the colony records. Finally, we investigated the consequences of inbreeding within the SNPRC colony and found clear evidence for increased rates of infant mortality and increased homozygosity of putatively deleterious alleles in inbred individuals.

Recent studies suggest that closely related species can accumulate substantial genetic and phenotypic differences despite ongoing gene flow, thus challenging traditional ideas regarding the genetics of speciation. Baboons (genus Papio) are Old World monkeys consisting of six readily distinguishable species. Baboon species hybridize in the wild, and prior data imply a complex history of differentiation and introgression. We produced a reference genome assembly for the olive baboon (Papio anubis) and whole-genome sequence data for all six extant species. We document multiple episodes of admixture and introgression during the radiation of Papio baboons, thus demonstrating their value as a model of complex evolutionary divergence, hybridization, and reticulation. These results help inform our understanding of similar cases, including modern humans, Neanderthals, Denisovans, and other ancient hominins.

Baboons (genus Papio) are broadly studied in the wild and in captivity. They are widely used as a non-human primate model for biomedical studies, and the Southwest National Primate Research Center (SNPRC) at Texas Biomedical Research Institute has maintained a large captive baboon colony for more than 50 years. Unlike other model organisms though, the genomic resources for baboons are severely lacking. This has hindered the progress of studies using baboons as a model for basic biology or human disease. Here, we describe a dataset of 100 high-coverage whole-genome sequences obtained from the mixed colony of olive (P. anubis) and yellow (P. cynocephalus) baboons housed at the SNPRC. These data provide a comprehensive catalog of common genetic variation in baboons, as well as a fine-scale genetic map. We show how the data can be used to learn about ancestry and admixture, and to correct errors in the colony records. Finally, we investigated the consequences of inbreeding within the SNPRC colony and found clear evidence for increased rates of juvenile mortality and increased homozygosity of putatively deleterious alleles in inbred individuals.

Inflammatory bowel disease (IBD) is a complex chronic inflammatory disorder of the gastrointestinal tract. Extracellular adenosine triphosphate (eATP) produced by the commensal microbiota and host cells activates purinergic signaling, promoting intestinal inflammation and pathology. Based on the role of eATP in intestinal inflammation, we developed yeast-based engineered probiotics that express a human P2Y2 purinergic receptor with up to a 1,000-fold increase in eATP sensitivity. We linked the activation of this engineered P2Y2 receptor to the secretion of the ATP-degrading enzyme apyrase, thus creating engineered yeast probiotics capable of sensing a pro-inflammatory molecule and generating a proportional self-regulated response aimed at its neutralization. These self-tunable yeast probiotics suppressed intestinal inflammation in mouse models of IBD, reducing intestinal fibrosis and dysbiosis with an efficacy similar to or higher than that of standard-of-care therapies usually associated with notable adverse events. By combining directed evolution and synthetic gene circuits, we developed a unique self-modulatory platform for the treatment of IBD and potentially other inflammation-driven pathologies. A synthetic yeast-based therapeutic that secretes an ATP-degrading enzyme in response to pro-inflammatory extracellular ATP in the gut reduces intestinal inflammation, fibrosis and dysbiosis in mouse models of colitis and enteritis., Author(s): Benjamin M. Scott [sup.1] [sup.2] [sup.3] [sup.9] , Cristina Gutiérrez-Vázquez [sup.4] , Liliana M. Sanmarco [sup.4] , Jessica A. da Silva Pereira [sup.4] , Zhaorong Li [sup.4] , Agustín [...]

Age is a prominent risk factor for cardiometabolic disease, often leading to heart structural and functional changes. However, precise molecular mechanisms underlying cardiac remodeling and dysfunction exclusively resulting from physiological aging remain elusive. Previous research demonstrated age‐related functional alterations in baboons, analogous to humans. The goal of this study is to identify early cardiac molecular alterations preceding functional adaptations, shedding light on the regulation of age‐associated changes. Unbiased transcriptomics of left ventricle samples are performed from female baboons aged 7.5–22.1 years (human equivalent ≈30–88 years). Weighted‐gene correlation network and pathway enrichment analyses are performed, with histological validation. Modules of transcripts negatively correlated with age implicated declined metabolism‐oxidative phosphorylation, tricarboxylic acid cycle, glycolysis, and fatty‐acid β‐oxidation. Transcripts positively correlated with age suggested a metabolic shift toward glucose‐dependent anabolic pathways, including hexosamine biosynthetic pathway (HBP). This shift is associated with increased glycosaminoglycan synthesis, modification, precursor synthesis via HBP, and extracellular matrix accumulation, verified histologically. Upregulated extracellular matrix‐induced signaling coincided with glycosaminoglycan accumulation, followed by cardiac hypertrophy‐related pathways. Overall, these findings revealed a transcriptional shift in metabolism favoring glycosaminoglycan accumulation through HBP before cardiac hypertrophy. Unveiling this metabolic shift provides potential targets for age‐related cardiac diseases, offering novel insights into early age‐related mechanisms. [ABSTRACT FROM AUTHOR]