Biology subjects

Vijay, N.

Publications and source records attributed to Vijay, N..

33 records · Page 2Linked to original sources

bioRxiv2023

Concurrent loss of ciliary genes WDR93 and CFAP46 in phylogenetically distant birds

The respiratory system is the primary route of infection for many contagious pathogens. Mucociliary clearance of inhaled pathogens is an important innate defense mechanism sustained by the rhythmic movement of epithelial cilia. To counter host defenses, viral pathogens target epithelial cells and cilia. For instance, the influenza virus modulates the expression of WDR93, a central ciliary apparatus C1d projection component. Lineage-specific prevalence of such host defense genes results in differential susceptibility. Our comparative analysis of [~]500 vertebrate genomes supports the widespread conservation of WDR93. However, we identified loss of the WDR93 in landfowl, geese, and other phylogenetically-independent bird species. Notably, species with WDR93 loss have concurrently lost another C1d component, CFAP46, through large segmental deletions. Understanding the consequences of such gene loss may provide insight into their role in host-pathogen interactions and benefit global pathogen surveillance efforts by prioritizing species missing host defense genes and identifying putative zoonotic reservoirs.

genomics↗

bioRxiv2022

HIV-1 Vpr induces ciTRAN to prevent transcriptional silencing of the provirus

The functional relevance of circular RNA (circRNA) expression in HIV-1 infection remains unclear. By developing a customized protocol involving direct RNA nanopore sequencing here, we captured circRNAs in their native state from HIV-1 infected T cells and identified ciTRAN, a circRNA modulator of HIV-1 Transcription. We show that HIV-1 infection of monocytic, T cell lines and primary CD4+ T cells induces ciTRAN expression in a Vpr-dependent manner. ciTRAN protein interactome analysis by proximity biotinylation and mass spectrometry identified SRSF-1 as a prominent interactor of the circular RNA. SRSF-1 is known to negatively regulate HIV-1 transcription, which the virus overcomes by a yet unknown mechanism. We demonstrate that HIV-1 Vpr induced ciTRAN sequesters SRSF1 away from the viral transcriptional complex to promote efficient viral transcription. Accordingly, ciTRAN depletion by CRISPR-Cas phenocopied the effects of SRSF1 overexpression and improved SRSF1 association with HIV-1 transcriptional complex. Finally, we show that an SRSF-1-inspired competing peptide can inhibit HIV-1 transcription regardless of ciTRAN induction. The hijacking of a host circRNA thus represents a new facet of primate lentiviruses in overcoming transmission bottlenecks.

microbiology↗

bioRxiv2022

Jack of all trades: genome assembly of Wild Jack and comparative genomics of Artocarpus

Known as breadfruits for their diverse nutritious fruits, the Artocarpus (Moraceae) genus is prized for its high-quality timber, medicinal value, and economic importance. Breadfruits are native to Southeast Asia but have been introduced to other continents. The most commonly cultivated species are Artocarpus heterophyllus (Jackfruit) and Artocarpus altilis (Breadfruit). With numerous smaller but nutritionally comparable fruits on a large tree, Artocarpus hirsutus, also called "Wild jack" or "Ayani" is an elusive forest species endemic to Indian Western Ghats. In this study, we sequenced and assembled the whole genome of Artocarpus hirsutus sampled from sacred groves of Coorg, India. We compared our Wild jack genome with previously published Jackfruit and Breadfruit genomes to decipher demography and evolution. Demographic history reconstruction indicates a stronger effect of habitat rather than phylogeny on the population histories of these plants. Repetitive genomic regions, especially LTR Copia, strongly affected the demographic trajectory of A. heterophyllus. Upon further investigation, we found a recent lineage-specific accumulation of LTR Copia in A. heterophyllus, which results in its larger genome size. Gene family evolution and signatures of selection identified multiple genes from starch, sucrose metabolism, plant hormone signal transduction, etc., in Artocarpus species. Our comparative genomic framework provides important insights by incorporating endemic species such as the Wild jack.

genomics↗

bioRxiv2022

Kadaknath chicken specific hitchhiking of BPIL with the FM locus

Black-bone-chicken (BBC) meat is popular for its distinctive taste and texture. A complex chromosomal rearrangement at the fibromelanosis (Fm) locus on the 20th chromosome results in increased expression of the endothelin-3 (EDN3) gene and is responsible for melanin hyperpigmentation in BBC. We use public long-read sequencing data of the silkie breed to resolve high-confidence haplotypes at the Fm locus spanning both Dup1 and Dup2 regions and establish that the Fm_2 scenario is correct of the three possible scenarios of the complex chromosomal rearrangement. The relationship between Chinese and Korean BBC breeds with Kadaknath native to India is underexplored. Our data from whole-genome re-sequencing establishes that all BBC breeds, including Kadaknath, share the complex chromosomal rearrangement junctions at the fibromelanosis (Fm) locus. We also identify two Fm locus proximal regions ([~]70Kb and [~]300 Kb) with signatures of selection unique to Kadaknath. These regions harbor several genes with protein-coding changes, with the Bactericidal/permeability-increasing-protein-like (BPIL) gene having two Kadaknath-specific changes within protein domains. Our results indicate that protein-coding changes in the BPIL gene hitchhiked with the Fm locus in Kadaknath due to close physical linkage. Identifying this Fm locus proximal selective sweep sheds light on the genetic distinctiveness of Kadaknath compared to other BBC.

evolutionary biology↗

bioRxiv2022

Genome divergence across the Indo-Burman arc: a tale of two peacocks

Exaggerated traits of the peacock are attributed to sexual selection. Yet, the two species of Asian peacock are conspicuously different in their plumage colouration and level of sexual dichromatism. Our integrative comparative study of bird calls, morphological differences and genomic divergence between the Indian blue peafowl and the green peafowl suggests a strong role of habitat differences in shaping species-specific changes. We estimate a recent (1-3 MYA) split of these species in the Pliocene or early Pleistocene, followed by intermittent periods of gene flow. Despite the relatively recent split, the high levels of genomic differentiation (FST [~] 0.6) mirror the divergence in morphological traits. Several genes involved in body patterning and colouration have accumulated protein-coding differences between the peacock species. Our estimates suggest genetic diversity in the widespread Indian peafowl ({theta}w [~] 0.0015) is comparable but slightly higher than in the endangered green peafowl ({theta}w [~] 0.0012). The ratio of genetic diversity on the Z chromosome to the autosomes (Z/A) is consistent with a polygynous mating system in the Indian peafowl compared to monogamy in the green peafowl. The Asian peacock species continue to provide exciting new insights into speciation and mating system evolution in the post-genomic era.

evolutionary biology↗

bioRxiv2022

Birth and Death in Terminal Complement Pathway

The cytolytic activity of the membrane attack complex (MAC) has a crucial role in the complement-mediated elimination of pathogens. Terminal complement pathway (TCP) genes encode the proteins that form the MAC. Although the TCP genes are well conserved within most vertebrate species, the early evolution of the TCP genes is poorly understood. Based on the comparative genomic analysis of the early evolutionary history of the TCP homologs, we evaluated four possible scenarios that could have given rise to the vertebrate TCP. Currently available genomic data support a scheme of complex sequential protein domain gains that may be responsible for the birth of the vertebrate C6 gene. The subsequent duplication and divergence of this vertebrate C6 gene formed the C7, C8, C8{beta}, and C9 genes. Compared to the widespread conservation of TCP components within vertebrates, we discovered that C9 has disintegrated in the genomes of galliform birds. Publicly available genome and transcriptome sequencing datasets of chicken from Illumina short read, PacBio long read, and Optical mapping technologies support the validity of the genome assembly at the C9 locus. In this study, we have generated a >120X coverage whole-genome Chromium 10x linked-read sequencing dataset for the chicken and used it to verify the loss of the C9 gene in the chicken. We find multiple CR1 (chicken repeat 1) element insertions within and near the remnant exons of C9 in several galliform bird genomes. The reconstructed chronology of events shows that the CR1 insertions occurred after C9 gene loss in an early galliform ancestor. Our study of C6 gene birth in an early vertebrate ancestor and C9 gene death in galliform birds provides insights into the evolution of the TCP.

immunology↗

bioRxiv2021

Recurrent erosion of COA1/MITRAC15 demonstrates gene dispensability in oxidative phosphorylation

Skeletal muscle fibers rely upon either oxidative phosphorylation or glycolytic pathway to achieve muscular contractions that power mechanical movements. Species with energy-intensive adaptive traits that require sudden bursts of energy have a greater dependency on fibers that use the glycolytic pathway. Glycolytic fibers have decreased reliance on OXPHOS and lower mitochondrial content compared to oxidative fibers. Hence, we hypothesized that adaptive gene loss might have occurred within the OXPHOS pathway in lineages that largely depend on glycolytic fibers. The protein encoded by the COA1/MITRAC15 gene with conserved orthologs found in budding yeast to humans promotes mitochondrial translation. We show that gene disrupting mutations have accumulated within the COA1/MITRAC15 gene in the cheetah, several species of galliforms, and rodents. The genomic region containing COA1/MITRAC15 is a well-established evolutionary breakpoint region in mammals. Careful inspection of genome assemblies of closely related species of rodents and marsupials suggests two independent COA1/MITRAC15 gene loss events co-occurring with chromosomal rearrangements. Besides recurrent gene loss events, we document changes in COA1/MITRAC15 exon structure in primates and felids. The detailed evolutionary history presented in this study reveals the intricate link between skeletal muscle fiber composition and dispensability of the chaperone-like role of the COA1/MITRAC15 gene.

evolutionary biology↗

bioRxiv2020

CoalQC - Quality control while inferring demographic histories from genomic data: Application to forest tree genomes

Estimating demographic histories using genomic datasets has proven to be useful in addressing diverse evolutionary questions. Despite improvements in inference methods and availability of large genomic datasets, quality control steps to be performed prior to the use of sequentially Markovian coalescent (SMC) based methods remains understudied. While various filtering and masking steps have been used by previous studies, the rationale for such filtering and its consequences have not been assessed systematically. In this study, we have developed a reusable pipeline called "CoalQC", to investigate potential sources of bias (such as repeat regions, heterogeneous coverage, and callability). First, we demonstrate that genome assembly quality can affect the estimation of demographic history using the genomes of several species. We then use the CoalQC pipeline to evaluate how different repeat classes affect the inference of demographic history in the plant species Populus trichocarpa. Next, we assemble a draft genome by generating whole-genome sequencing data for Mesua ferrea (sampled from Western Ghats, India), a multipurpose forest plant distributed across tropical south-east Asia and use it as an example to evaluate several technical (sequencing technology, PSMC parameter settings) and biological aspects that need to be considered while comparing demographic histories. Finally, we collate the genomic datasets of 14 additional forest tree species to compare the temporal dynamics of Ne and find evidence of a strong bottleneck in all tropical forest plants during Mid-Pleistocene glaciations. Our findings suggest that quality control prior to the use of SMC based methods is important and needs to be standardised.

evolutionary biology↗

bioRxiv2020

Coevolution of retroviruses with SERINCs following whole-genome duplication divergence

The SERINC gene family comprises of five paralogs in humans of which SERINC3 and SERINC5 inhibit HIV-1 infectivity and are counteracted by Nef. The origin of this anti-retroviral activity, its prevalence among the remaining paralogs, and its ability to target retroviruses remain largely unknown. Here we show that despite their early divergence, the anti-retroviral activity is functionally conserved among four human SERINC paralogs with SERINC2 being an exception. The lack of activity in human SERINC2 is associated with its post-whole genome duplication (WGD) divergence, as evidenced by the ability of pre-WGD orthologs from yeast, fly, and a post-WGD-proximate SERINC2 from coelacanth to inhibit nef-defective HIV-1. Intriguingly, potent retroviral factors from HIV-1 and MLV are not able to relieve the SERINC2-mediated particle infectivity inhibition, indicating that such activity was directed towards other retroviruses that are found in coelacanth (like foamy viruses). However, foamy-derived vectors are intrinsically resistant to the action of SERINC2, and we show that a foamy virus envelope confers this resistance. Despite the presence of weak arms-race signatures, the functional reciprocal adaptation among SERINC2 and SERINC5 and, in response, the emergence of antagonizing ability in foamy virus appears to have resulted from a long-term conflict with the host.

microbiology↗

bioRxiv2019

Signatures of relaxed selection in the CYP8B1 gene of birds and mammals

The CYP8B1 gene is known to catalyse reactions that determine the ratio of primary bile salts and the loss of this gene has recently been linked to lack of cholic acid in the bile of naked-mole rats, elephants and manatees using forward genomics approaches. We screened the CYP8B1 gene sequence of more than 200 species and test for relaxation of selection along each terminal branch. The need for retaining a functional copy of the CYP8B1 gene is established by the presence of a conserved open reading frame across most species screened in this study. Interestingly, the dietary switch from bovid to cetacean species is accompanied by an exceptional ten amino-acid extension at the C-terminal end through a single base frame-shift deletion. We also verify that the coding frame disrupting mutations previously reported in the elephant are correct, are shared by extinct Elephantimorpha species and coincide with the dietary switch to herbivory. Relaxation of selection in the CYP8B1 gene of the wombat (Vombatus ursinus) also corresponds to drastic change in diet. In summary, our forward genomics based screen of bird and mammal species identifies recurrent changes in the selection landscape of the CYP8B1 gene concomitant with a change in dietary lipid content.

evolutionary biology↗

bioRxiv2019

Comparative analysis of corrected tiger genome provides clues to their neuronal evolution

The availability of completed and draft genome assemblies of tiger, leopard, and other felids provides an opportunity to gain comparative insights on their unique evolutionary adaptations. However, genome-wide comparative analyses are very sensitive to errors in genome sequences and thus require accurate genomic assemblies for reliable evolutionary insights. In this study, while analyzing the tiger genome, we found almost one million erroneous substitutions in the coding and non-coding region of the genome affecting 4,472 genes, hence, biasing the current understanding of tiger evolution. Moreover, these errors produced several misleading observations in previous studies. Thus, to gain insights into the tiger evolution, we corrected the erroneous bases in the genome assembly and gene set of tiger, which was also validated by resequencing of a Bengal tiger genome and transcriptome. A comprehensive evolutionary analysis was performed using 10,920 orthologs from nine mammalian species including the corrected gene sets of tiger and leopard, and using five different methods at three hierarchical levels i.e. felids, Panthera, and tiger. The unique genetic changes in tiger revealed that the genes showing the signatures of adaptation in tiger were enriched in development and neuronal functioning. Specifically, the genes belonging to Notch signalling pathway, which is among the most conserved pathways involved in embryonic and neuronal development, were found to be significantly diverged in tiger in comparison to the other mammals. Our findings suggest the role of adaptive evolution in neuronal functions and development processes, which correlates well with the presence of exceptional traits such as sensory perception, strong neuro-muscular coordination, and hypercarnivorous behavior in tiger.

genomics↗

bioRxiv2018

A hypothetical new role for single-stranded DNA binding proteins in the immune system

The breadth of the host range of single-stranded DNA (ssDNA) viruses is roughly comparable to the host range of double-stranded DNA viruses (dsDNA). Yet, general ssDNA sensing receptors that activate the immune system have not been unequivocally identified while numerous dsDNA sensing receptors are known. Here, we hypothesize that some of the Single-Stranded DNA Binding (SSB) proteins may act as receptors that detect single-stranded DNA from pathogens and activate the innate immune system. As the first test of our hypothesis, we checked whether human genes that are known to bind to ssDNA are potentially interferon-regulated. Out of the 102 human genes that are known to have ssDNA binding ability 23 genes show a more than two-fold increase in gene expression upon interferon treatment. Single-stranded DNA viruses are pathogens of not only animals but also of plants and protozoans. We used this information to further prioritize our candidate list to ssDNA binding genes that are common between the model plant Arabidopsis thaliana and humans. Based on these strategies, we shortlist several promising candidate genes including the HMGB1 gene which could act as a ssDNA sensor that activates the immune system. Agreeably though we cannot establish a definitive role for these genes as ssDNA sensors of the immune system as yet, our preliminary analysis suggests the potential existence of ssDNA binding protein-like receptors (SLRs) that are worth investigating further.

immunology↗

bioRxiv2018

Genome Sequence of Indian Peacock Reveals the Peculiar Case of a Glittering Bird

The unique ornamental features and extreme sexual traits of Peacock have always intrigued the scientists. However, the genomic evidence to explain its phenotype are yet unknown. Thus, we report the first genome sequence and comparative analysis of peacock with the available high-quality genomes of chicken, turkey, duck, flycatcher and zebra finch. The candidate genes involved in early developmental pathways including TGF-{beta}, BMP, and Wnt signaling pathway, which are also involved in feather patterning, bone morphogenesis, and skeletal muscle development, showed signs of adaptive evolution and provided useful clues on the phenotype of peacock. The innate and adaptive immune components such as complement system and T-cell response also showed signs of adaptive evolution in peacock suggesting their possible role in building a robust immune system which is consistent with the between species predictions of Hamilton-Zuk hypothesis. This study provides novel genomic and evolutionary insights into the molecular understanding towards the phenotypic evolution of Indian peacock.

genomics↗

bioRxiv2017

Population genomic analysis reveals contrasting demographic changes of two closely related dolphin species in the last glacial

Population genomic data can be used to infer historical effective population sizes (Ne), which help study the impact of past climate changes on biodiversity. Previous genome sequencing of one individual of the common bottlenose dolphin Tursiops truncatus revealed an unusual, sharp rise in Ne during the last glacial, raising questions about the reliability, generality, underlying cause, and biological implication of this finding. Here we first verify this result by additional sampling of T. truncatus. We then sequence and analyze the genomes of its close relative, the Indo-Pacific bottlenose dolphin T. aduncus. The two species exhibit contrasting demographic changes in the last glacial, likely through actual changes in population size and/or alterations in the level of gene flow among populations. Our findings demonstrate that even closely related species can have drastically different responses to climatic changes, making predicting the fate of individual species in the ongoing global warming a serious challenge.

evolutionary biology↗

bioRxiv2017

Genome-wide signatures of genetic variation within and between populations - a comparative perspective

Genome-wide screens of genetic variation can reveal signatures of population-specific selection implicated in adaptation and speciation. Yet, unrelated processes such as linked selection arising as a consequence of genome architecture can generate comparable signatures across taxa. To investigate prevalence and phylogenetic stability of linked selection, we took a comparative approach utilizing population-level data from 444 re-sequenced genomes of three avian clades spanning 50 million years of evolution. Levels of nucleotide diversity ({pi}),population-scaled recombination rate ({rho}), genetic differentiation (FST, PBS) and sequence divergence (Dxy) were remarkably similar in syntenic genomic regions across clades. Elevated local genetic differentiation was associated with inferred centromere and sub-telomeric regions. Our results support a role of linked selection shaping genome-wide heterogeneity in genetic diversity within and between clades. The long-term conservation of diversity landscapes and stable association with genomic features make the outcome of this evolutionary process in part predictable.

evolutionary biology↗