Biology subjects

Gandham, R. K.

Publications and source records attributed to Gandham, R. K..

9 recordsLinked to original sources

bioRxiv2026

SUMO modulates meiotic crossover rates between and within vertebrate species

Crossing over during meiosis drives genetic diversity and ensures the accurate segregation of homologous chromosomes. Variation in the rate of crossing over has been linked to evolutionary divergence and environmental adaptability, shaping fitness and responses to selective pressures. Despite its significance, the molecular mechanisms underlying this variation remain poorly understood. Crossover sites are selected from a large pool of potential sites initiated by programmed DNA double-strand breaks. Post-translational modification by SUMO (Small Ubiquitin-like Modifier) has been implicated in this process. Here, we show that crossover rate, chromosome length, and abundance of chromosome-associated SUMO are positively correlated across a range of vertebrate species, including mouse, chicken, pig, cattle, sheep, and goat. Crossover variation between goat breeds across the Indian subcontinent was also positively correlated with chromosomal SUMO level. Furthermore, modulating SUMO levels in cultured goat spermatocytes altered crossover frequency. Cumulatively, these observations point to a central role for SUMO in mediating crossover variation both between and within vertebrate species.

cell biology↗

bioRxiv2025

Multi-omics analysis uncovers differential growth kinetics of Japanese Encephalitis Virus in human and porcine macrophages

Japanese encephalitis virus (JEV), a mosquito-borne neurotropic virus, poses a significant threat to juvenile humans, while causing mild symptoms in pigs, except piglets. Pigs with high viremia are amplifier hosts, whereas humans with lower viremia are dead-end hosts. The molecular mechanisms behind the varying viremia levels in pigs and humans remain poorly understood. A comparative multi-omics study was conducted on JEV-infected macrophages, the early site of JEV replication in both species. We identified 24 key determinants potentially regulating viral growth. Functional validation of three antiviral factors - LGALS1, ssc-miR-133a-3p, and hsa-miR-3614-5p, and two proviral factors - MIF and VMP1, in macrophages showed that the upregulation of MIF and VMP1, and downregulation of ssc-miR-133a-3p, enhanced JEV replication in pigs. In contrast, the downregulation of MIF and VMP1 and upregulation of hsa-miR-3614-5p reduced JEV replication in human macrophages. These findings provide critical insights into JEV infection and its species-specific dynamics.

microbiology↗

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↗

bioRxiv2022

Changes in m6A RNA methylation of goat lung following PPRV infection

Peste des petits ruminants (PPR) is an acute, highly contagious viral disease of goats and sheep, caused by the Peste des petits ruminants virus (PPRV). Earlier studies suggest the involvement of diverse regulatory mechanisms in PPRV infection. Methylation at N6 of Adenosine called m6A is one such RNA modification that influences various physiological and pathological phenomena. As the lung tissue represents the primary target organ of PPRV, the present study explored the m6A changes and their functional significance in PPRV disease pathogenesis. m6A-seq analysis revealed 1289 m6A peaks to be significantly altered in PPRV infected lung in comparison to normal lung, out of which 975 m6A peaks were hypomethylated and 314 peaks were hypermethylated. Importantly, hypomethylated genes were enriched in Interleukin-4 and Interleukin-13 signaling and various processes associated with extracellular matrix organization. Further, of the 843 differentially m6A containing cellular transcripts, 282 transcripts were also found to be differentially expressed. Functional analysis revealed that these 282 transcripts are significantly enriched in signaling by Interleukins, extracellular matrix organization, cytokine signaling in the immune system, signaling by receptor tyrosine kinases, and Toll-like Receptor Cascades. We also found m6A reader HNRNPC and the core component of methyltransferase complex METTL14 to be highly upregulated than the m6A readers - HNRNPA2B1 and YTHDF1 at the transcriptome level. These findings suggest that alteration in m6A landscape following PPRV is implicated in diverse processes including the Interleukin signaling.

microbiology↗

bioRxiv2020

Systems Biology behind immunoprotection of both Sheep and Goats after Sungri/96 PPRV vaccination

Immune response is a highly coordinated cascade involving all the subsets of PBMCs. In this study, RNA-Seq analysis of PBMC subsets - CD4+, CD8+, CD14+, CD21+ and CD335+ cells from day 0 and day 5 of Sungri/96 Peste des Petits Ruminants vaccinated sheep and goats was done to delineate the systems biology behind immune - protection of the vaccine in sheep and goats. Assessment of the immune response processes enriched by the differentially expressed genes in all the subsets suggested a strong dysregulation towards development of early inflammatory microenvironment, which is very much required for differentiation of monocytes to macrophages, and for activation and migration of dendritic cells into the draining lymph nodes. The protein - protein interaction networks among the antiviral molecules (IFIT3, ISG15, MX1, MX2, RSAD2, ISG20, IFIT5 and IFIT1) and common DEGs across PBMCs subsets in both the species identified ISG15 to be an ubiquitous hub, that helps in orchestrating antiviral host response against PPRV. IRF7 was found to be the key master regulator activated in most of the subsets in sheep and goats. Most of the pathways were found to be inactivated in B - lymphocytes of both the species indicating that 5 dpv is too early a time point for the B - lymphocytes to react. The cell mediated immune response and humoral immune response pathways were found more enriched in goats than in sheep. Though, animals from both the species survived the challenge, a contrast in pathway activation was observed in CD335+ cells. ImportancePeste des petits ruminants (PPR) by PPRV is an OIE listed acute, contagious transboundary viral disease of small ruminants. Attenuated Sungri/96 PPRV vaccine used all over India against this PPR, provides long-lasting robust innate and adaptive immune response. The early antiviral response was found mediated through type I interferon independent ISGs expression. However, systems biology behind this immune response is unknown. In this study, in vivo transcriptome profiling of PBMC subsets (CD4+, CD8+, CD14+, CD21+ and CD335+) in vaccinated goats and sheep (at 5 days of post vaccination) was done to understand this systems biology. Though there are a few differences in the systems biology across cells (specially the NK cells) between sheep and goats, the co-ordinated response that is inclusive of all the cell subsets was found to be towards induction of strong innate immune response, which is needed for an appropriate adaptive immune response.

systems biology↗

bioRxiv2020

Prediction analysis of SARS-COV-2 entry in Livestock and Wild animals

BackgroundSARS-CoV-2 is a viral pathogen causing life-threatening disease in human. Interaction between spike protein of SARS-CoV-2 and ACE2 receptor on the cells is a potential factor in the infectivity of a host. The interaction of SARS-CoV-2 spike receptor-binding domain with its receptor - ACE2, in different hosts was evaluated to understand and predict viral entry. The protein and nucleotide sequences of ACE2 were initially compared across different species to identify key differences among them. The ACE2 receptor of various species was homology modeled (6LZG, 6M0J, and 6VW1 as a reference), and its binding ability to the spike ACE2 binding domain of SARS-CoV-2 was assessed. Initially, the spike binding parameters of ACE2 of known infected and uninfected species were compared with each Order (of animals) as a group. Finally, a logistic regression model vis-a-vis the spike binding parameters of ACE2 (considering data against 6LZG and 6M0J) was constructed to predict the probability of viral entry in different hosts. ResultsPhylogeny and alignment comparison did not lead to any meaningful conclusion on viral entry in different hosts. Out of several spike binding parameters of ACE2, a significant difference between the known infected and uninfected species was observed for six parameters. However, these parameters did not specifically categorize the Orders (of animals) into infected or uninfected. The logistic regression model constructed revealed that in the mammalian class, most of the species of Carnivores, Artiodactyls, Perissodactyls, Pholidota, and Primates had high probability of viral entry. However, among the primates, African Elephant had low probability of viral entry. Among rodents, hamsters were highly probable for viral entry with rats and mice having a medium to low probability. Rabbits have a high probability of viral entry. In Birds, ducks have a very low probability, while chickens seemed to have medium probability and turkey showed the highest probability of viral entry. ConclusionsMost of the species considered in this study showed high probability of viral entry. This study would prompt us to closely follow certain species of animals for determining pathogenic insult by SARS-CoV-2 and for determining their ability to act as a carrier and/or disseminator.

microbiology↗

bioRxiv2020

HSPs, Ubiquitins and Antioxidants aid in Heat Tolerance in Tharparkar Indicine cattle

Transcriptome profiling of Vrindavani and Tharparkar cattle revealed that more numbers of genes dysregulated in Vrindavani than in Tharparkar. A contrast in gene expression was observed with 18.5 % of upregulated genes in Vrindavani were downregulated in Tharparkar and 17.5% upregulated genes in Tharparkar were downregulated in Vrindavani. Functional annotation of genes differentially expressed in Tharparkar and Vrindavani revealed that the systems biology in Tharparkar is moving towards counteracting the effects due to heat stress. Unlike Vrindavani, Tharparkar is not only endowed with higher expression of the scavengers (UBE2G1, UBE2S, and UBE2H) of misfolded proteins but also with protectors (VCP, Serp1, and CALR) of naive unfolded proteins. Further, higher expression of the antioxidants in Tharparkar enables it to cope up with higher levels of free radicals generated as a result of heat stress. In this study we found relevant genes dysregulated in Tharparkar in the direction that can counter heat stress.

physiology↗