Biology subjects

Manu, S.

Publications and source records attributed to Manu, S..

6 recordsLinked to original sources

bioRxiv2025

Genomic signatures of terrestrial adaptation in air-breathing catfishes (Clariidae)

Air-breathing catfishes of the family Clariidae exhibit extraordinary adaptations that enable them to survive outside water for extended periods, yet the genetic and genomic basis of these adaptations remain poorly understood. To study these adaptations, we sequenced and assembled two high-quality genomes of two clariid species, Clarias gariepinus and Clarias dussumieri and compare them with previously available genomes of 23 catfish species across nine families. By reconstructing the whole-genome phylogeny and examining patterns of positive selection and gene family evolution, we found unique signatures associated with terrestrial adaptation in clariids. Our analysis revealed that a high proportion of genes were positively selected in clariids, that play critical roles in hypoxia tolerance, thermoregulation, metabolism, and DNA repair, which are key traits for terrestrial adaptation. Additionally, we observed significant expansions in gene families, including Myoglobin (involved in oxygen transport), immunity-related genes, and xenobiotic degradation pathways, highlighting their importance in environmental resilience and detoxification. Together, these findings provide a comprehensive understanding of the genomic changes facilitating the terrestrial adaptation of clariids. This study also highlights the contribution of genome evolution to their resilience, adaptability to novel environments, and invasiveness, offering valuable insights into the genetic basis of ecological niche diversification.

evolutionary biology↗

bioRxiv2025

The 3' Region of the ZPA Regulatory Sequence (ZRS) is required for activity and contains a critical E-box

1BackgroundDuring development, Hand2 and Hoxd13 transcription factors (TFs) regulate Sonic hedgehog (Shh) expression in the zone of polarizing activity (ZPA) in the distal posterior limb mesoderm. The ZPA regulatory sequence (ZRS) is a conserved, limb-specific enhancer that controls Shh expression. The ZRS can be divided into 5, central, and 3 subdomains, each with an E-box site that can bind basic helix-loop-helix (bHLH) TFs like Hand2. In addition, two Hoxd13 sites are present in the 5 and central subdomains. Hand2 purportedly binds the ZRS through the central E-box, and both Hand2 and Hoxd13 have been shown to activate the ZRS in vitro. We hypothesized that the central E-box was required for activity, while the other E-boxes and Hoxd13 sites localize ZRS activity to the distal posterior limb mesoderm. MethodsTo identify the functional role of each subdomain, we generated three ZRS fragments (5, central, and 3) and combined fragment constructs to test subdomain collective contributions. Additionally, we disrupted the five binding sites, alone or in concert, using site-directed mutagenesis. All ZRS constructs were cloned into a GFP reporter and evaluated in an in vivo chicken limb bioassay. We validated our findings using select ZRS constructs in transgenic mice. ResultsWe found that the 3 fragment was necessary for ZRS activity, while the 5 and central fragments had no activity alone or when combined. However, combining the 3 fragment with the 5 fragment restored robust activity. Further, mutation of all five binding sites markedly reduced ZRS activity. Reinstating each of the Hoxd13 sites restored focal activity, while restoring the 5 and central E-boxes had little effect. However, the 3 E-box proved sufficient for robust activity even in the absence of the other four binding sites. ConclusionsOur data indicate that the ZRS 3, not the central, subdomain is necessary for activity and contains the 3 E-box that Hand2 likely uses to induce Shh expression, while the 5 and central E-boxes appear to be inhibitory. Our data also suggest that the Hoxd13 binding sites promote localized activity within the ZPA.

developmental biology↗

bioRxiv2023

Genomic potential and evolution of Dissimilatory Nitrate Reduction to Ammonium in Cyanobacteria

Cyanobacteria play an important role in primary production and nitrogen fixation. Although Cyanobacteria are well-known diazotrophic organisms, their role in other steps Nitrogen Cycle is obscure. Screening of Cyanobacterial genomes from cultured and unculturable species can help identify potentially novel functions. In this study, we assembled Cyanobacterial genomes from metagenomic data generated from environmental DNA isolated from a brackish water lagoon (Chilika, India). We annotated these Cyanobacterial metagenome-assembled genomes (MAG) for all the encoded functions using KEGG Orthology. We found two high-quality Cyanobacterial MAGs containing the nirBD gene and nifH and nifD genes involved in the nitrogen cycle. nirBD encodes for the Dissimilatory Nitrate Reduction to Ammonium (DNRA) activity, a function previously not ascribed to Cyanobacteria. We validated the presence of NirBD in publicly available isolate genomes of Cyanobacteria and examined its evolution in the phylum by phylogenetic reconciliation of species and gene trees. Our analysis revealed that both horizontal gene transfers and speciation events contributed to the dispersal of the nirBD gene in Cyanobacteria. We observed that mostly filamentous Cyanobacteria served as ancestral donors in horizontal gene transfer events. Further, we found that the nirBD gene is under a purifying selection pressure in Cyanobacteria. This study demonstrates the genomic potential and evolution of DNRA activity in Cyanobacteria for the utilisation of nitrate in the ecosystem which can help these organisms to cope with extreme environmental conditions. It expands our overall comprehension of the contribution of Cyanobacteria in the biogeochemical cycling in aquatic ecosystems.

microbiology↗

bioRxiv2023

The landscape of tolerated genetic variation in humans and primates

Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole genome sequencing data for 809 individuals from 233 primate species, and identified 4.3 million common protein-altering variants with orthologs in human. We show that these variants can be inferred to have non-deleterious effects in human based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases. One Sentence SummaryDeep learning classifier trained on 4.3 million common primate missense variants predicts variant pathogenicity in humans.

genomics↗

bioRxiv2023

A global catalog of whole-genome diversity from 233 primate species

The rich diversity of morphology and behavior displayed across primate species provides an informative context in which to study the impact of genomic diversity on fundamental biological processes. Analysis of that diversity provides insight into long-standing questions in evolutionary and conservation biology, and is urgent given severe threats these species are facing. Here, we present high coverage whole-genome data from 233 primate species representing 86% of genera and all 16 families. This dataset was used, together with fossil calibration, to create a nuclear DNA phylogeny and to reassess evolutionary divergence times among primate clades. We found within-species genetic diversity across families and geographic regions to be associated with climate and sociality, but not with extinction risk. Furthermore, mutation rates differ across species, potentially influenced by effective population sizes. Lastly, we identified extensive recurrence of missense mutations previously thought to be human-specific. This study will open a wide range of research avenues for future primate genomic research. One-Sentence SummaryThe whole genome sequences of 233 primate species provide insight into the determinants of genetic diversity, phylogenomics, and human uniqueness.

genomics↗

bioRxiv2018

SYSTEMATIC ANALYSES OF AUTOSOMAL RECOMBINATION RATES FROM THE 1000 GENOMES PROJECT UNCOVERS THE GLOBAL RECOMBINATION LANDSCAPE IN HUMANS

BackgroundMeiotic recombination plays an important role in evolution by shuffling different alleles along the chromosomes, thus generating the genetic diversity across generations that is vital for adaptation. The plasticity of recombination rates and presence of hotspots of recombination along the genome has attracted much attention over two decades due to their contribution to the evolution of the genome. Yet, the variation in genome-wide recombination landscape and the differences in the location and strength of hotspots across worldwide human populations remains little explored.\n\nResultsWe make use of the untapped linkage disequilibrium (LD) based genetic maps from the 1000 Genomes Project (1KGP) to perform in-depth analyses of finescale variation in the autosomal recombination rates across 20 human populations to uncover the global recombination landscape. We have generated a detailed map of human recombination landscape comprising of a comprehensive set of 88,841 putative hotspots and 80,129 coldspots with their respective strengths across populations, about 2/3rd of which were previously unknown. We have validated and assessed the number of historical putative hotspots derived from the patterns of LD that are currently active in the contemporary populations using a recently published high-resolution pedigree-based genetic map, constructed and refined using 3.38 million crossovers from various populations. For the first time, we provide statistics regarding the conserved, shared, and unique hotspots across all the populations studied.\n\nConclusionsOur analysis yields clusters of continental groups, reflecting their shared ancestry and genetic similarities in the recombination rates that are linked to the migratory and evolutionary histories of the populations. We provide the genomic locations and strengths of hotspots and coldspots across all the populations studied which are a valuable set of resources arising out our analyses of 1KGP data. The findings are of great importance for further research on human hotspots as we approach the dusk of retiring HapMap-based resources.

evolutionary biology↗