Biology subjects

Neupane, M.

Publications and source records attributed to Neupane, M..

6 recordsLinked to original sources

bioRxiv2026

Linking geography and mutation profiles across goat species

Recent studies have characterised the mutational profile across multiple mammalian species, highlighting substantial differences across lineages. However, none of these studies investigated whether mutation profiles and geography are significantly correlated. In this study, we present a multi-genome alignment spanning several Capra taxa, reconstruct the ancestral genome of Capra hircus and use it to characterize the mutational profiles across multiple Capra species by using the 1000 genomes VarGoats dataset. Results confirmed that the scale of differences among Capra species largely reflects their phylogenetic relationships, in particular with the Bezoar being genetically closer to domestic goats than to other wild species. Subsequently, we correlated the mutational profile and the geographical origin of the different individuals. In particular, ACG>ATG changes have the strongest correlation with longitude (r = -0.79, P-value = 3.02*10-204), while TCA>TGA are strongly correlated with latitude (r = -0.51, P-value = 4.30*10-63). We highlight how sequential dinucleotide mutations (SDMs) place cosmopolitan breeds closer to the sampling location, rather than the country of origin, showing how the recent relocation of cosmopolitan breeds to new continents is reshaping the genome of these animals. Finally, we used the mutational profile to predict the coordinate of origin of each animal in the dataset. In conclusion, we show the important role that geography had in shaping the genomes of domestic goats.

genomics↗

bioRxiv2025

Inferring domestic goat demographic history through ancient genome imputation

Goats were among the earliest managed animals, making them a natural model to explore the genetic consequences of domestication. However, a challenge in ancient genomic analysis is the relatively low genome coverage for most samples, limiting analysis to pseudohaploid genotypes. Genotype imputation offers potential to alleviate this limitation by improving information content and accuracy in low coverage genomes. To test this we used published high coverage (>8x) goat palaeogenomes, imputing downsampled genomes using the VarGoats dataset (1,372 individuals) as a reference panel. Measuring concordance between imputed and high coverage genotypes, we find high concordance after filtering for common (>5%), high confidence variants, with 0.5x genomes reaching >0.97 concordance. There is a trade-off between coverage, genotype probability (GP) thresholds, and genotype recovery, where higher coverage and more lenient GP thresholds result in higher recovery, and a reduction in heterozygous false-positive rates with stricter thresholds. We then imputed 36 goat palaeogenomes with [≥]0.5x coverage to examine runs-of-homozygosity (ROH) and identity-by-descent (IBD) patterns. Using a novel approach combining ROH profiles across tools, we find that among Neolithic goats, ROH increases with distance from the Zagros Mountains, suggesting a large effect of the initial dispersal of managed herds. Inbreeding levels decrease across Southwest Asia in more recent periods. IBD mirrored this pattern, with less relatedness in the early herding site of Ganj Dareh compared to higher relatedness in goats from later in the dispersal process. These findings provide insights into the genetic consequences of early goat management on demography, and confirm the utility of imputation in leveraging low coverage palaeogenomes. SignificancePaleogenomics offers crucial insight into how animals were domesticated, but poor DNA preservation in ancient remains often limits the reach of genetic analyses. We utilise a cutting-edge technique, genotype imputation, to recover missing genetic information from ancient low coverage goat genomes and shine light on their domestication process. Early domestic goats showed low overall runs-of-homozygosity (ROH) and relatedness. We find that during the Neolithic, runs-of-homozygosity (ROH) and relatedness among goats increased, likely a consequence of the movement of herds beyond their natural range by humans. Inbreeding levels decline in more recent periods, potentially due to expanded herd sizes, animal trade networks, or improved husbandry practices. These findings challenge long-standing assumptions about domestication bottlenecks and highlight how ancient DNA can be used to uncover complex evolutionary histories, even from low coverage ancient samples.

genomics↗

bioRxiv2025

Genome assemblies of Indian desi cattle reveals hotspots of rearrangements and immune-related genetic diversity

India, home to the worlds largest cattle population, hosts native dairy breeds essential to its agricultural economy because of their adaptability and resilience. This study characterizes the genomes of five prominent breeds Gir, Kankrej, Red Sindhi, Sahiwal and Tharparkar, highlighting their unique genomic characteristics. The de novo assemblies ranged from 2.70-2.78 Gb in size, with 90% of the genomes assembled in just 56 to 1,663 scaffolds. The use of reference-guided scaffolding further enhanced these genomes, resulting in 93.3-96.7% pseudomolecule coverage with strong BUSCO scores (94.1-95.5%). Comparative analyses revealed 87-95% synteny with the Brahman genome and identified 19.84-153.16 Mb of structural rearrangements per genome, including inversions, translocations, and duplications. Synteny diversity analysis uncovered 10,643 perfectly collinear regions spanning 87.3 Mb and 6,622 hotspots of rearrangement (HOT regions) covering 55.18 Mb. These HOT regions, characterized by high synteny diversity, were significantly enriched with immune-related genes. Moreover, immune-related gene clusters, including MHC, NKC, and LRC, were identified within HOT regions in the desi reference genome. Our findings provide valuable insights into the genetic diversity of desi cattle breeds. The high-quality genome assemblies generated in this study will serve as valuable resources for future research in genetic improvement, disease resistance, and environmental adaptation.

genomics↗

bioRxiv2024

Constructing a Draft Indian Cattle Pangenome Using Short-Read Sequencing

BackgroundIndian cattle known as desi cattle, renowned for their adaptability to harsh environments and diverse phenotypic traits, represent a valuable genetic resource. While reference genome assemblies have been instrumental in advancing cattle genomics, they often fail to capture the full spectrum of genetic variation present within diverse populations. To address this limitation, we aimed to construct a pangenome for desi cattle by identifying and characterizing Non-Reference Novel Sequences (NRNS). FindingsWe sequenced 68 desi cattle genomes representing seven distinct breeds, generating 48.35 billion short reads. A PanGenome Analysis (PanGA) pipeline was developed in Bash scripts to process these data to identify NRNS missing in the reference genome. A total of 13,065 NRNS with a cumulative length of [~]41 Mbp were identified that exhibited substantial variation across the population. These NRNS were found to be exclusive to Indian desi cattle, matching only 4.1% with the Chinese indicine pangenome. However, a significant proportion ([~]40%) of NRNS displayed ancestral origins within the Bos genus. These sequences were enriched in genic regions, suggesting functional roles, and were associated with quantitative trait loci (QTLs), particularly for milk production. Compared to a single reference genome, the pangenome approach significantly enhanced read mapping accuracy, reduced spurious SNP calls, and facilitated the discovery of novel genetic variants. ConclusionsThis study has successfully established a within-species cattle pangenome specifically focused on desi cattle breeds from India. Our findings highlight the importance of pangenome based analyses for understanding the complex genetic architecture of desi cattle.

genomics↗

bioRxiv2024

Advancing the Indian Cattle Pangenome: Characterizing Non-Reference Sequences in Bos indicus

BackgroundIndia, with the worlds largest cattle population and more than 50 registered breeds of Bos indicus, stands as a vital reservoir of genetic diversity. However, the abundant diversity among Indian cattle breeds highlights the inadequacy of a single reference sequence to represent the entire genomic content of desi cattle. We recognize the need to capture the genomic differences within the Bos indicus population as a whole, and specifically within the dairy cattle subset by identifying non-reference sequences and constructing a pangenome. FindingFive representative genomes of prominent dairy breeds, including Gir, Kankrej, Tharparkar, Sahiwal, and Red Sindhi, were sequenced using 10X Genomics Linked-Read technology. Assemblies generated from these linked-reads ranged from 2.70 Gb to 2.77 Gb,comparable to the Bos indicus Brahman reference genome. A pangenome of Bos indicus cattle was constructed by comparing the newly assembled genomes with the reference using alignment and graph-based methods, revealing 8 Mb and 17.7 Mb of novel sequence respectively. A confident set of 6,844 Non-Reference Unique Insertions (NUIs) spanning 7.57 Mbs was identified through both methods, representing the pangenome of Indian Bos indicus breeds. Comparative analysis with previously published pangenomes unveiled 2.8 Mb (37%) commonality with the Chinese indicine pangenome and only 1% commonality with the Bos taurus pangenome. Among these, 2,312 NUIs - encompassing [~]2 Mb, were commonly found in 98 samples of the 5 breeds and designated as Bos indicus Common Insertions (BICIs) in the population. Furthermore, 926 BICIs were identified within 682 protein-coding genes, 54 long non-coding RNAs (LncRNA), and 18 pseudogenes. These protein-coding genes were enriched for functions such as chemical synaptic transmission, cell junction organization, cell-cell adhesion, and cell morphogenesis. The protein-coding genes were found in various prominent Quantitative Trait Loci (QTL) regions, suggesting potential roles of BICIs in traits related to milk production, reproduction, exterior, health, meat, and carcass. Notably, 63.21% of the bases within the BICIs call set contained interspersed repeats, predominantly LINEs. Additionally,70.28% of BICIs are shared with other domesticated and wild species, highlighting their evolutionary significance. ConclusionThis is the first report unveiling a robust set of NUIs defining the pangenome of Bos indicus breeds of India. The analyses contribute valuable insights into the genomic landscape of desi cattle breeds.

genomics↗

bioRxiv2017

Detecting past and ongoing natural selection among ethnically Tibetan women at high altitude in Nepal

Adaptive evolution in humans has rarely been characterized for its whole set of components, i.e. selective pressure, adaptive phenotype, beneficial alleles and realized fitness differential. We combined approaches for detecting selective sweeps and polygenic adaptations and for mapping the genetic bases of physiological and fertility phenotypes in approximately 1000 indigenous ethnically Tibetan women from Nepal, adapted to high altitude. We performed genome-wide association analysis and tests for polygenic adaptations which showed evidence of positive selection for alleles associated with more pregnancies and live births and evidence of negative selection for those associated with higher offspring mortality. Lower hemoglobin level did not show clear evidence for polygenic adaptation, despite its strong association with an EPAS1 haplotype carrying selective sweep signals.

genetics↗