When natural populations split and migrate to different environments, they may experience different selection pressures that can lead to local adaptation. To capture the genomic patterns of a local selective sweep, we develop XP‐nSL, a genomic scan for local adaptation that compares haplotype patterns between two populations. We show that XP‐nSL has power to detect ongoing and recently completed hard and soft sweeps, and we then apply this statistic to search for evidence of adaptation to high altitude in rhesus macaques. We analyze the whole genomes of 23 wild rhesus macaques captured at high altitude (mean altitude > 4000 m above sea level) to 22 wild rhesus macaques captured at low altitude (mean altitude < 500 m above sea level) and find evidence of local adaptation in the high‐altitude population at or near 303 known genes and several unannotated regions. We find the strongest signal for adaptation at EGLN1, a classic target for convergent evolution in several species living in low oxygen environments. Furthermore, many of the 303 genes are involved in processes related to hypoxia, regulation of ROS, DNA damage repair, synaptic signaling, and metabolism. These results suggest that, beyond adapting via a beneficial mutation in one single gene, adaptation to high altitude in rhesus macaques is polygenic and spread across numerous important biological systems.

Word Count (300 max): 216 36 Total Word Count (5000 max): 3813 Abstract 50When natural populations split and migrate to different environments, they may 51 experience different selection pressures that can lead to local adaptation. For aerobic 52 life, the low atmospheric oxygen content of high altitude living presents a special 53 challenge and a strong selection pressure. Searching for evidence of adaptation to high 54 altitude, we compare the whole genomes of 23 wild rhesus macaques captured at high 55 altitude (mean altitude > 4000m above sea level) to 22 wild rhesus macaques captured 56 at low altitude (mean altitude < 500m above sea level). To capture the genomic patterns 57 of a positive selective sweep, we develop XP-nSL, a haplotype-based genomic scan for 58 differential local adaptation with power to detect ongoing and recently completed hard 59 and soft sweeps. We find evidence of local adaptation in the high-altitude population at 60 or near 303 known genes and several unannotated regions. We find the strongest signal 61 for adaptation at EGLN1, a classic target for convergent evolution in several species 62 living in low oxygen environments. Furthermore, many of the 303 genes are involved in 63 processes related to hypoxia, regulation of ROS, DNA damage repair, synaptic 64 signaling, and metabolism. These results suggest that, beyond adapting via a beneficial 65 mutation in one single gene, adaptation to high altitude in rhesus macaques is polygenic 66 and spread across numerous important biological systems. 67 Impact Summary 68Extreme environments pose a challenge to life on multiple fronts. Very high-69altitude environments are one such example, with low atmospheric oxygen, increased 70 ultraviolet light exposure, harsh temperatures, and reduced nutrition availability. In spite 71 of these challenges, many plants and animals, including humans, have genetically 72 adapted to cope with these hardships. Here we study a population of rhesus macaques 73 living at high altitude and compare their genomic patterns with those of a population 74 living much closer to sea level, searching for evidence of genetic changes that are 75 indicative of adaptation to their environment. 76When positive selection is ongoing or a beneficial mutation has recently fixed in a 77 population, genetic diversity is reduced in the vicinity of the adaptive allele, and we 78 expect to observe long homozygous haplotypes at high frequency. Here we develop a 79 statistic that summarizes these expected patterns and compares between two 80 populations in order to search for evidence of adaptation that may have occurred in one 81 but not the other. We implement this statistic in a popular and easy-to-use software 82 package. 83We find evidence for adaptation at a critical gene that helps control physiological 84 response to low-oxygen, one that has been the target of repeated convergent evolution 85 across many species. We also find evidence for positive selection across a range of 86 traits, including metabolic and neurological. This ...

13Genital divergence contributes to reproductive barriers between species. Emergence of a 14 novel accessory structure, the baculum, has independently evolved and been lost throughout 15 mammalian evolution, purportedly driven by sexual selection. In primates, the longest recorded 16 baculum belongs to Macaca arctoides, the bear macaque. This species has been proposed to be of 17 homoploid hybrid origin via ancient hybridization between representatives from the fascicularis 18 and sinica species groups. To investigate the evolutionary origins of the bear macaque and its 19 unique morphology, we used whole genome sequences to quantify gene flow and phylogenetic 20 relationships in 10 individuals from 5 species, including the bear macaque (n=3), and two species 21 each from the sinica (n=3) and fascicularis (n=4) species groups. The results of these analyses were 22 concordant, and identified 608 genes in the bear macaque that supported both clustering between 23 M. arctoides and the sinica group (topo2) and had shared derived alleles between species from the 24 two groups. Similarly, 361 genes supported both clustering between M. arctoides and the 25 fascicularis group (topo3) and had shared derived alleles between both groups. Further, sliding 26 window analysis of phylogenetic relationships revealed 53% of the genomic regions supported 27 placement of M. arctoides in the sinica species group (topo2), 16% supported placement in the 28 fascicularis species group (topo3), and 11% supported M. arctoides in a grouping distinct from the 29 sinica and fascicularis groups (topo1). Genomic regions with topo1 were intersected with 30 previously identified QTL for mouse baculum morphology, and 47 genes were found, including five 31 of sixteen major candidate loci that govern mouse baculum variation (KIF14, KIAA0586, RHOJ, 32 TGM2, and DACT1). Although baculum morphology in the bear macaque is diverged from its parent 33 taxa, it most closely resembles that of the fascicularis group. Outliers of shared ancestry from the 34 fascicularis species group located within these same QTL regions overlap with the gene BMP4, 35 which is an important component of the hedgehog signaling pathway that controls gonadogenesis. 36Two additional outlier genes (one shared with each species group) outside of the baculum QTL are 37 known to interact with BMP4, suggesting this pathway may be involved in baculum morphology in 38 primates. These results highlight how the mosaic ancestry of the bear macaque could explain its 39 unique baculum evolution and collectively contribute to reproductive isolation. 40 Introductory Paragraph 41In mammals, the baculum has extreme morphological variability, a dynamic evolutionary 42 history characterized by repeated gain and loss, and is often used in species identification. The bear 43 macaque has divergent genital morphology, including the longest baculum among all primates, and 44 is proposed to have evolved via ancient hybrid speciation. Here, population genetic and 45 phylogenomic approaches were used to e...

In general, beef cattle long-distance transportation from cow-calf operations to feedlots or from feedlots to abattoirs is a common situation in the beef industry. The aim of this study was to determine the effect of rumen-protected methionine (RPM) supplementation on a proposed gene network for muscle fatigue, creatine synthesis (CKM), and reactive oxygen species (ROS) metabolism after a transportation simulation in a test track. Angus × Simmental heifers (n = 18) were stratified by body weight (408 ± 64 kg; BW) and randomly assigned to dietary treatments: 1) control diet (CTRL) or 2) control diet + 8 gr/hd/day of topdressed rumen-protected methionine (RPM). After an adaptation period to Calan gates, animals received the mentioned dietary treatment consisting of Bermuda hay ad libitum and a soy hulls and corn gluten feed based supplement. After 45 days of supplementation, animals were loaded onto a trailer and transported for 22 hours (long-term transportation). Longissimus muscle biopsies, BW and blood samples were obtained on day 0 (Baseline), 43 (Pre-transport; PRET), and 46 (Post-transport; POST). Heifers' average daily gain did not differ between baseline and PRET. Control heifer's shrink was 10% of BW while RPM heifers shrink was 8%. Serum cortisol decreased, and glucose and creatine kinase levels increased after transportation, but no differences were observed between treatments. Messenger RNA was extracted from skeletal muscle tissue and gene expression analysis was performed by RT-qPCR. Results showed that AHCY and DNMT3A (DNA methylation), SSPN (Sarcoglycan complex), and SOD2 (Oxidative Stress-ROS) were upregulated in CTRL between baseline and PRET and, decreased between pre and POST while they remained constant for RPM. Furthermore, CKM was not affected by treatments. In conclusion, RPM supplementation may affect ROS production and enhance DNA hypermethylation, after a long-term transportation.

The transition from a high forage to a high concentrate diet is an important milestone for beef cattle moving from a stocker system to the feedlot. However, little is known about how this transition affects the rumen epithelial gene expression. This study assessed the effects of the transition from a high forage to a high concentrate diet as well as the transition from a high concentrate to a high forage diet on a variety of genes as well as ruminal papillae morphology in rumen fistulated Jersey steers. Jersey steers (n = 5) were fed either a high forage diet (80% forage and 20% grain) and transitioned to a high concentrate diet (20% forage and 80% grain) or a high concentrate diet (40% forage and 60% grain) and transitioned to a high forage diet (100% forage). Papillae from the rumen were collected for histology and RT‐qPCR analysis. Body weight had a tendency for significant difference (p = .08). Histological analysis did not show changes in papillae length or width in steers transitioning from a high forage to a high concentrate diet or vice versa (p > .05). Genes related to cell membrane structure (CLDN1, CLDN4, DSG1), fatty acid metabolism (CPT1A, ACADSB), glycolysis (PFKL), ketogenesis (HMGCL, HMGCS2, ACAT1), lactate/pyruvate (LDHA), oxidative stress (NQO1), tissue growth (AKT3, EGFR, EREG, IGFBP5, IRS1) and the urea cycle (SLC14A1) were considered in this study. Overall, genes related to fatty acid metabolism (ACADSB) and growth and development (AKT3 and IGFBP5) had a tendency for a treatment × day on trial interaction effect. These profiles may be indicators of rumen epithelial adaptations in response to changes in diet. In conclusion, these results indicate that changes in the composition of the diet can alter the expression of genes with specific functions in rumen epithelial metabolism.

Genital divergence is thought to contribute to reproductive barriers by establishing a “lock‐and‐key" mechanism for reproductive compatibility. One such example, Macaca arctoides , the bear macaque, has compensatory changes in both male and female genital morphology as compared to close relatives. M . arctoides also has a complex evolutionary history, having extensive introgression between the fascicularis and sinica macaque species groups. Here, phylogenetic relationships were analyzed via whole‐genome sequences from five species, including M . arctoides , and two species each from the putative parental species groups. This analysis revealed ~3x more genomic regions supported placement in the sinica species group as compared to the fascicularis species group. Additionally, introgression analysis of the M . arctoides genome revealed it is a mosaic of recent polymorphisms shared with both species groups. To examine the evolution of their unique genital morphology further, the prevalence of candidate genes involved in genital morphology was compared against genome‐wide outliers in various population genetic metrics of diversity, divergence, introgression, and selection, while accounting for background variation in recombination rate. This analysis identified 67 outlier genes, including several genes that influence baculum morphology in mice, which were of interest since the bear macaque has the longest primate baculum. The mean of four of the seven population genetic metrics was statistically different in the candidate genes as compared to the rest of the genome, suggesting that genes involved in genital morphology have increased divergence and decreased diversity beyond expectations. These results highlight specific genes that may have played a role in shaping the unique genital morphology in the bear macaque.

Different participants generally located distant among them compose the U.S. beef production chain, therefore shipping is required for cattle at least once in their lifespan. The aim of this study was to determine the effect of Rumen-Protected Methionine (RPM) supplementation on muscle fatigue gene network, creatine synthesis (CKM), and Reactive Oxygen Species (ROS) metabolism after a transportation simulation in a 1.7-miles oval test track. Angus heifers (n = 18) were stratified by body weight (408 ± 64 kg; BW) and randomly assigned to dietary treatments: 1) control diet (CTRL), and 2) control diet + rumen-protected methionine (RPM). After a successful adaptation period to Calan gates, animals received a common diet of Bermuda hay ad libitum and a soy hulls and corn gluten feed based supplement. After 45 days under supplementation, animals were loaded onto a 32 × 7 ft. trailer and transported for 22 hours. Skeletal muscle biopsies, BW and blood samples were obtained on day 0 (Baseline), 43 (Pre-transport, “PRET”), and 45 (Post-transport, “POST”). Heifer’s average daily gain did not differ between Baseline and PRET (P = 0.41). Control heifer’s shrink was 8% of BW while RPM heifers shrink was 10% (P = 0.29). Cortisol level decreased after transportation, but no differences were observed between treatments (P = 0.94). Messenger RNA was extracted from skeletal muscle tissue and gene expression analysis was performed by RT-qPCR. Results showed that AHCY (Creatine synthesis pathway), SSPN (Sarcoglycan complex), DNMT3A (DNA Methylation), and SOD2 (Oxidative Stress-ROS) were upregulated (P &lt; 0.05) in CTRL between baseline and PRET and, decreased between PRET and POST (P &lt; 0.05) while they remained constant for RPM. Furthermore, CKM was not affected by treatments (P = 0.11). In conclusion, muscle fatigue related genes were not affected by RPM. Although, RPM could affect ROS production, after a long-term transportation.

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