staff

Xuexue Liu

Senior Research Assistant in MuseumLab

  • T: -
  • office -

  • Comparison of muscle metabolomics between two Chinese horse breeds Frontiers in veterinary science vol. 10 1162953. 5 May. 2023, doi:10.3389/fvets.2023.1162953

    abstract

    With their enormous muscle mass and athletic ability, horses are well-positioned as model organisms for understanding muscle metabolism. There are two different types of horse breeds-Guanzhong (GZ) horses, an athletic breed with a larger body height (~148.7 cm), and the Ningqiang pony (NQ) horses, a lower height breed generally used for ornamental purposes-both inhabited in the same region of China with obvious differences in muscle content. The main objective of this study was to evaluate the breed-specific mechanisms controlling muscle metabolism. In this study, we observed muscle glycogen, enzyme activities, and LC-MS/MS untargeted metabolomics in the gluteus medius muscle of six, each of GZ and NQ horses, to explore differentiated metabolites that are related to the development of two muscles. As expected, the glycogen content, citrate synthase, and hexokinase activity of muscle were significantly higher in GZ horses. To alleviate the false positive rate, we used both MS1 and MS2 ions for metabolite classification and differential analysis. As a result, a total of 51,535 MS1 and 541 MS2 metabolites were identified, and these metabolites can separate these two groups from each other. Notably, 40% of these metabolites were clustered into lipids and lipid-like molecules. Furthermore, 13 significant metabolites were differentially detected between GZ and NQ horses (fold change [FC] value ≥ 2, variable important in projection value ≥1, and Q value ≤ 0.05). They are primarily clustered into glutathione metabolism (GSH, p = 0.01), taurine, and hypotaurine metabolism (p < 0.05) pathways. Seven of the 13 metabolites were also found in thoroughbred racing horses, suggesting that metabolites related to antioxidants, amino acids, and lipids played a key role in the development of skeleton muscle in horses. Those metabolites related to muscle development shed a light on racing horses' routine maintenance and improvement of athletic performance.

    view more details on Pubmed

  • Whole-genome identification of transposable elements reveals the equine repetitive element insertion polymorphism in Chinese horses Animal genetics vol. 54,2 (2023): 144-154. doi:10.1111/age.13277

    abstract

    Transposable elements (TEs) are diverse, abundant, and complicated in genomes. They not only can drive the genome evolution process but can also act as special resources for adaptation. However, little is known about the evolutionary processes that shaped horses. In this work, 126 horse assemblages involved in most horse breeds in China were used to investigate the patterns of TE variation for the first time. By using RepeatMasker and melt software, we found that the horse-specific short interspersed repetitive elements family, equine repetitive elements (ERE1), exhibited polymorphisms in horse genomes. Phylogenetic analysis based on these ERE1 loci (minor allele frequency ≥0.05) revealed three major horse groups, namely, those in northern China, southern China, and Qinghai-Tibetan, which mirrors the result determined by SNPs to some extent. The present ERE1 family emerged ~0.26 to 1.77 Mya ago, with an activity peak at ~0.49 Mya, which matches the early stage of the horse lineage and decreases after the divergence of Equus caballus and Equus ferus przewalskii. To detect the functional ERE1(s) associated with adaptation, locus-specific branch length, genome-wide association study, and absolute allele frequency difference analyses were conducted and resulted in two common protein-coding genes annotated by candidate ERE1s. They were clustered into the vascular smooth muscle contraction (p = 0.01, EDNRA) and apelin signalling pathways (p = 0.02, NRF1). Notably, ERE1 insertion into the EDNRA gene showed a higher association with adaptation among southern China horses and other horses in 15 populations and 451 individuals (p = 4.55 e-8). Our results provide a comprehensive understanding of TE variations to analyse the phylogenetic relationships and traits relevant to adaptive evolution in horses.

    view more details on Pubmed

  • Early dispersal of domestic horses into the Great Plains and northern Rockies Science (New York, N.Y.) vol. 379,6639 (2023): 1316-1323. doi:10.1126/science.adc9691

    abstract

    The horse is central to many Indigenous cultures across the American Southwest and the Great Plains. However, when and how horses were first integrated into Indigenous lifeways remain contentious, with extant models derived largely from colonial records. We conducted an interdisciplinary study of an assemblage of historic archaeological horse remains, integrating genomic, isotopic, radiocarbon, and paleopathological evidence. Archaeological and modern North American horses show strong Iberian genetic affinities, with later influx from British sources, but no Viking proximity. Horses rapidly spread from the south into the northern Rockies and central plains by the first half of the 17th century CE, likely through Indigenous exchange networks. They were deeply integrated into Indigenous societies before the arrival of 18th-century European observers, as reflected in herd management, ceremonial practices, and culture.

    view more details on Pubmed

  • DNA methylation-based profiling of horse archaeological remains for age-at-death and castration iScience vol. 26,3 106144. 5 Feb. 2023, doi:10.1016/j.isci.2023.106144

    abstract

    Age profiling of archaeological bone assemblages can inform on past animal management practices, but is limited by the fragmentary nature of the fossil record and the lack of universal skeletal markers for age. DNA methylation clocks offer new, albeit challenging, alternatives for estimating the age-at-death of ancient individuals. Here, we take advantage of the availability of a DNA methylation clock based on 31,836 CpG sites and dental age markers in horses to assess age predictions in 84 ancient remains. We evaluate our approach using whole-genome sequencing data and develop a capture assay providing reliable estimates for only a fraction of the cost. We also leverage DNA methylation patterns to assess castration practice in the past. Our work opens for a deeper characterization of past husbandry and ritual practices and holds the potential to reveal age mortality profiles in ancient societies, once extended to human remains.

    view more details on Pubmed

  • mapDATAge: a ShinyR package to chart ancient DNA data through space and time Bioinformatics (Oxford, England) vol. 38,16 (2022): 3992-3994. doi:10.1093/bioinformatics/btac425

    abstract

    Summary: Ancient DNA datasets are increasingly difficult to visualize for users lacking computational experience. Here, we describe mapDATAge, which aims to provide user-friendly automated modules for the interactive mapping of allele, haplogroup and/or ancestry distributions through space and time. mapDATAge enhances collaborative data sharing while assisting the assessment and reporting of spatiotemporal patterns of genetic changes. Availability and implementation: mapDATAge is a Shiny R application designed for exploring spatiotemporal patterns in ancient DNA data through a graphical user interface. It is freely available under GNU Public License in Github: https://github.com/xuefenfei712/mapDATAge.

    view more details on Pubmed

  • A single-nucleotide mutation within the TBX3 enhancer increased body size in Chinese horses Current biology : CB vol. 32,2 (2022): 480-487.e6. doi:10.1016/j.cub.2021.11.052

    abstract

    Chinese ponies are endemic to the mountainous areas of southwestern China and were first reported in the archaeological record at the Royal Tomb of Zhongshan King, Mancheng, dated to approximately ∼2,100 YBP.1 Previous work has started uncovering the genetic basis of size variation in western ponies and horses, revealing a limited number of loci, including HMGA2,2LCORL/NCAPG,3ZFAT, and LASP1.4,5 Whether the same genetic pathways also drive the small body size of Chinese ponies, which show striking anatomical differences to Shetland ponies,6 remains unclear.2,7 To test this, we combined whole-genome sequences of 187 horses across China. Statistical analyses revealed top association between genetic variation at the T-box transcription factor 3 (TBX3) and the body size. Fine-scale analysis across an extended population of 189 ponies and 574 horses narrowed down the association to one A/G SNP at an enhancer region upstream of the TBX3 (ECA8:20,644,555, p = 2.34e-39). Luciferase assays confirmed the single-nucleotide G mutation upregulating TBX3 expression, and enhancer-knockout mice exhibited shorter limbs than wild-type littermates (p < 0.01). Re-analysis of ancient DNA data showed that the G allele, which is most frequent in modern horses, first occurred some ∼2,300 years ago and rose in frequency since. This supports selection for larger size in Asia from approximately the beginning of the Chinese Empire. Overall, this study characterized the causal regulatory mutation underlying small body size in Chinese ponies and revealed size as one of the main selection targets of past Chinese breeders.

    view more details on Pubmed

  • EPAS1 Gain-of-Function Mutation Contributes to High-Altitude Adaptation in Tibetan Horses Molecular biology and evolution vol. 36,11 (2019): 2591-2603. doi:10.1093/molbev/msz158

    abstract

    High altitude represents some of the most extreme environments worldwide. The genetic changes underlying adaptation to such environments have been recently identified in multiple animals but remain unknown in horses. Here, we sequence the complete genome of 138 domestic horses encompassing a whole altitudinal range across China to uncover the genetic basis for adaptation to high-altitude hypoxia. Our genome data set includes 65 lowland animals across ten Chinese native breeds, 61 horses living at least 3,300 m above sea level across seven locations along Qinghai-Tibetan Plateau, as well as 7 Thoroughbred and 5 Przewalski's horses added for comparison. We find that Tibetan horses do not descend from Przewalski's horses but were most likely introduced from a distinct horse lineage, following the emergence of pastoral nomadism in Northwestern China ∼3,700 years ago. We identify that the endothelial PAS domain protein 1 gene (EPAS1, also HIF2A) shows the strongest signature for positive selection in the Tibetan horse genome. Two missense mutations at this locus appear strongly associated with blood physiological parameters facilitating blood circulation as well as oxygen transportation and consumption in hypoxic conditions. Functional validation through protein mutagenesis shows that these mutations increase EPAS1 stability and its hetero dimerization affinity to ARNT (HIF1B). Our study demonstrates that missense mutations in the EPAS1 gene provided key evolutionary molecular adaptation to Tibetan horses living in high-altitude hypoxic environments. It reveals possible targets for genomic selection programs aimed at increasing hypoxia tolerance in livestock and provides a textbook example of evolutionary convergence across independent mammal lineages.

    view more details on Pubmed

Xuexue Liu is a maître-assistant researcher at the GENEV department of the University of Geneva. She has long been committed to the excavation and protection of Chinese domestic horse germplasm resources. She acquired both bioinformatic analysis and experimental skills during her doctoral study at the Chinese Academy of Agriculture Sciencesin China. She was then hired as a MSCA postdoctoral researcher at the CAGT lab of the Centre national de la recherche scientifique (CNRS) in Toulouse, funded by the European Union’s Horizon 2020 research with additional support from anInternational Postdoctoral Exchange Fellowship Program in China to support her postdoctoral research work. Xuexue’s aptitudes in ancient DNA will bring our projects in collaboration with the CAGT lab on demogenetics of reindeers and horses one step further.