Biology subjects

Sil, M.

Publications and source records attributed to Sil, M..

13 recordsLinked to original sources

bioRxiv2026

Mathematical genomics of SRY proteins and their associated HMG-Box domains across mammals

Male sex determination in mammals depends on sex-determining region Y (SRY), a transcription factor whose high-mobility group box (HMG box) binds and bends DNA to activate SOX9. The divergent N- and C-terminal domains lack sequence homology and have been dismissed as passive linkers, yet alignment-based homology cannot reveal whether they retain a hidden compositional grammar. We applied quantitative genomics to 65 full-length mammalian SRY proteins and 38 HMG-box subsequences across 75 mammals, integrating amino acid and dipeptide compositions, Shannon entropy, dominant-residue profiles, hydropathy-based n-gram spectra, longest hydropathy stretches, and cumulative proximity. The HMG box is tightly constrained: basic residues dominated, cysteine was nearly absent, entropy clustered near 4.0, polar content averaged 58.44\%, and 25 of 38 HMG boxes shared 57.97\% polar residues, whereas full-length SRY varied more, with rodents showing high polar and glutamine-rich profiles and cetaceans low polar content. Proximity-based clustering was more taxonomically consistent at the HMG level, while terminal regions blurred domain-level signals. Across 65 SRY proteins and 38 HMG domains, intrinsic disorder was the dominant predicted state, and a polyQ-rich rodent SRY illustrated how low-complexity repeats can produce misleading ordered predictions, underscoring the need for consensus disorder analysis in rapidly evolving intrinsically disordered regions. Cumulative proximity analysis identified \textit{Bos taurus} and \textit{Bos grunniens} as the only pair proximally clustered at both the full-length SRY and SRY-HMG levels, establishing multivariate proximity as a stringent criterion of compositional similarity satisfied by a single mammalian pair. These results suggest that SRY and its HMG box each carry a distinct compositional grammar, quantifiable only through alignment-independent signatures, with compositional individuality being the rule rather than the exception. These quantitative signatures provide a framework for interpreting SRY variation, assessing clinical mutations, and understanding evolutionary pressures shaping sex determination. Denser taxon sampling, structural modeling, and experimental tests are needed to clarify whether HMG-box drift and terminal-region variation affect DNA binding, bending, or reproductive function.

bioinformatics↗

bioRxiv2026

Quantitative Deciphering of Mammalian Histamine Receptors through Mathematical Genomics

Histamine receptors (HRH1-HRH4) are G-protein coupled receptors (GPCRs) that mediate essential physiological functions, including neurotransmission, gastric acid secretion, immune regulation, and presynaptic autoregulation. Despite their importance, systematic comparative analyses across mammalian histamine receptor sequences remain scarce. In this study, we performed a comprehensive evaluation of HRH1-HRH4 across multiple mammalian species, integrating sequence homology, invariant residue mapping, amino acid substitutions, compositional frequencies, Shannon entropy, polystring distributions, intrinsic disorder profiling, and phylogenetic clustering. HRH2 and HRH1 were highly conserved among primates, HRH3 showed strong cohesion within rodents, while HRH4 exhibited pronounced divergence consistent with immune-related specialization. Invariant residues localized to transmembrane helices and activation motifs (D107, W428/Y431, NPxxY), underscoring strict evolutionary constraints on ligand binding, receptor stability, and G-protein coupling. Substitutions were confined to non-essential lipid-facing and loop regions, predominantly conservative in nature, enabling diversification without disrupting the GPCR fold. Amino acid frequency and entropy analyses revealed hydrophobic dominance with subtype-specific enrichment of polar residues, while disorder profiling identified HRH1 as the most dynamic and HRH2 as the most structurally constrained. Polystring analysis highlighted conserved motifs (WWW, PP) alongside subtype- and species-specific repeats, reflecting evolutionary strategies balancing receptor stability with adaptive flexibility. Phylogenetic clustering confirmed subtype-specific cohesion, with HRH3 and HRH4 forming compact clades, HRH1 showing moderate dispersion, and HRH2 forming the most isolated cluster. Collectively, these findings demonstrate that mammalian histamine receptor evolution is governed by conserved biophysical cores and selective variability, offering insights into structural conservation, functional diversification, and translational relevance for drug design and model selection.

bioinformatics↗

bioRxiv2025

Nuclear and mitochondrial genome assemblies of Indrella ampulla, a terrestrial gastropod endemic to the Western Ghats

Indrella ampulla is a polymorphic, brightly coloured, forest-dwelling land snail endemic to the Western Ghats of India. Studying and understanding evolutionary processes occurring within this species has remained a challenge largely due to a paucity of genomic resources. We present high-quality annotated nuclear and mitochondrial genome assemblies of I. ampulla. The nuclear genome is assembled through a hybrid approach using Illumina short reads and Oxford Nanopore long reads, with an N50 value of 632 kb and 90.3% BUSCO genome completeness. The mitogenome is 13,887 bp long. The demographic history reconstruction based on the genomic data exhibits signatures of population decline during the last 100,000 years. This genome will aid in deciphering the colour polymorphism in I. ampulla and augmenting the general understanding of the evolution of gastropods. SignificanceIndrella ampulla is a terrestrial gastropod endemic to the Western Ghats biodiversity hotspot, and exhibits color polymorphism. The genome of I. ampulla provides a valuable resource for understanding molluscan biology, coloration genetics, adaptation, and other evolutionary processes. Our historical demographic analysis offers insights into past population dynamics of this species endemic to the Western Ghats of India, contributing to broader research on biodiversity patterns in tropical ecosystems. The bioinformatics pipeline used in this study provides a reliable framework for assembling high-quality genomes with long-read coverage as low as 10X, making it especially useful for gastropods and other species where obtaining high coverage data is a challenge. Overall, this genome will complement future studies in phylogenomics, comparative genomics, and conservation of molluscs.

genomics↗

bioRxiv2025

Proximal relationships of moonlighting Proteins in Escherichia coli: a mathematical genomic perspective

Moonlighting proteins in Escherichia coli (E.coli) perform multiple independent functions without altering their primary amino acid sequence, challenging the "one gene-one enzyme" hypothesis. Bacterial proteins serve various functions, including host cell adhesion, extracellular matrix interaction, and immune modulation, while also supporting essential physiological processes within the bacteria. Identifying these proteins in pathogens and tracking their genetic changes is crucial for understanding bacterial survival and virulence. A quantitative understanding of these proteins is pivotal as it enables the identification of specific patterns and relationships between amino acid composition, protein stability, and functional versatility. This study quantitatively analyzes fifty E. coli moonlighting proteins, focusing on their structural and functional features. Key findings include variability in amino acid composition, with alanine predominating, and a preference for non-polar residues, which may enhance protein stability. Quantitative features analyses identified seven distinct proximal sets, reflecting the proteins spatial arrangements of amino acids, structural diversity, and functional roles in processes such as metabolism, stress response, and gene regulation. These results deepen our understanding of the multifunctionality of E. coli moonlighting proteins, indicating their adaptability and implications for bacterial survival and pathogenicity.

genomics↗

bioRxiv2024

Methuselah Proteins in Longevity: Unraveling Their Impact Through Mathematical Genomics

This study provides a quantitative and comprehensive analysis of 18 Methuselah (mth) protein variants from fruit flies, focusing on their evolutionary relationships, structural features, and functional roles in aging and longevity. Phylogenetic analysis identified two major clades of mth proteins, with the first clade indicating conserved functions across Drosophila species and the second clade reflecting gene duplication and diversification. The study found five distinct functional subclasses of mth proteins through amino acid frequency and poly-string analyses, linked to their structural diversity and role in longevity. Structural topology and post-translational modifications reveal similarities with G-protein-coupled receptors (GPCRs), suggesting that mth proteins are crucial for signal transduction and cellular health. Variability in propeptide cleavage sites and intrinsic protein disorder further highlight adaptive roles in signaling. The findings underscore the importance of a quantitative and comprehensive approach to studying Methuselah genes, offering insights into their functional versatility and evolutionary dynamics. This enhanced quantitative understanding contributes to advancing research on aging and longevity.

genomics↗

bioRxiv2023

The Distal-Proximal Relationships Among the Human Moonlighting Proteins: Evolutionary hotspots and Darwinian checkpoints

Moonlighting proteins, known for their ability to perform multiple, often unrelated functions within a single polypeptide chain, challenge the traditional "one gene, one protein, one function" paradigm. As organisms evolved, their genomes remained relatively stable in size, but the introduction of post-translational modifications and sub-strategies like protein promiscuity and intrinsic disorder enabled multifunctionality. Enzymes, in particular, exemplify this phenomenon, engaging in unrelated processes alongside their primary catalytic roles. This study employs a systematic, quantitative informatics approach to shed light on human moonlighting protein sequences. Phylogenetic analyses of human moonlighting proteins are presented, elucidating the distal-proximal relationships among these proteins based on sequence-derived quantitative features. The findings unveil the captivating world of human moonlighting proteins, urging further investigations in the emerging field of moonlighting proteomics, with the potential for significant contributions to our understanding of multifunctional proteins and their roles in diverse cellular processes and diseases.

genomics↗

bioRxiv2023

Serial dilution shapes genetic variation and defines conservation units in Asian elephants

Asian elephants (Elephas maximus) are the largest extant terrestrial megaherbivores native to Asia, with 60% of their wild population found in India. Despite ecological and cultural importance, their population genetic structure and diversity, demographic history, and ensuing implications for management/conservation remain understudied. We analysed 34 whole genomes (between 11X - 32X) from most known elephant landscapes in India and identified five management/conservation units corresponding to elephants in Northern (Northwestern/Northeastern) India, Central India and three in Southern India. Our genetic data reveal signatures of serial colonisation, and a dilution of genetic diversity from north to south of India. The Northern populations diverged from other populations more than 70,000 years ago, have higher genetic diversity, and low inbreeding/high effective size (Pi = 0.0016{+/-}0.0001; FROH> 1MB= 0.09{+/-}0.03). Two of three populations in Southern India (South of Palghat Gap: SPG, and South of Shencottah Gap:SSG) have low diversity and are inbred, with very low effective population sizes compared to current census sizes (Pi = 0.0014{+/-}0.00009 and 0.0015{+/-}0.0001; FROH> 1MB= 0.25{+/-}0.09 and 0.17{+/-}0.02). Analyses of genetic load reveals purging of potentially high-effect insertion/deletion (indel) deleterious alleles in the Southern populations and potential dilution of all deleterious alleles from north to south in India. However, despite dilution and purging for the damaging mutation load in Southern India, the load that remains is homozygous. High homozygosity of deleterious alleles, coupled with low neutral genetic diversity make these populations (SPG and SSG) high priority for conservation attention. Most surprisingly, our study suggests that patterns of genetic diversity and genetic load can correspond to geographic signatures of serial founding events, even in large, highly mobile, endangered mammals.

evolutionary biology↗

bioRxiv2023

Biology of Coital Behavior: Looking Through the Lens of Mathematical Genomics

Research has shown that genetics and epigenetics regulate mating behavior across multiple species. Previous studies have generally focused on the signaling pathways involved and spatial distribution of the associated receptors. However a thorough quantitative characterization of the receptors involved may offer deeper insight into mating behavioral patterns. Here oxytocin, arginine-vasopressin 1a, dopamine 1, and dopamine 2 receptors were investigated across 76 vertebrate species. The receptor sequences were characterized by polarity-based randomness, amino acid frequency-based Shannon entropy and Shannon sequence variability, intrinsic protein disorder, binding affinity, stability and pathogenicity of homology-based SNPs, structural and physicochemical features. Hierarchical clustering of species was derived based on structural and physicochemical features of the four receptor sequences separately, which eventually led to proximal relationships among 29 species. Humans were found to be significantly distant phylogenetically from the prairie voles, a representative of monogamous species based on coital behavior. Furthermore, the mouse (polygamous), the prairie deer mouse (polygamous), and the prairie vole (monogamous) although being proximally related (based on quantitative genomics of receptors), differed in their coital behavioral pattern, mostly, due to behavioral epigenetic regulations. This study adds a perspective that receptor genomics does not directly translate to behavioral patterns.

genomics↗

bioRxiv2022

Possible Functional Proximity of Various Organisms Based on Taste Receptors Genomics

Taste is one of the essential senses in providing the organism a faithful representation of the external world. Taste perception is responsible for basic food and drink appraisal and bestows the organism with valuable discriminatory power. Umami and sweet are "good" tastes that promote consumption of nutritive food, whereas bitter and sour are "bad" tastes that alert the organism to toxins and low pH, promoting rejection of foods containing harmful substances. Not every animal has the same sense of taste as humans. Variation in the taste receptor genes contributes to inter and intra organism differences of taste (sweet/bitter) sensation and preferences. Therefore a deeper understanding was needed to comprehend taste perception by various vertebrates and accordingly elucidate a possible proximity among them. In this study, a total 20 Type-1 (sweet) and 189 Type-2 (bitter) taste receptor complete-amino acid sequences were taken from the 20 vertebrate organisms (18 mammalian, 1 aves, and 1 amphibian). Among 10 primates, 8 including humans were very close based on genomics of taste receptors and rodent organisms viz. the rat and mouse were away from them. This investigation throws light on the similitude and dissimilitude of perception of sweet and bitter taste among 20 different organisms, steered by quantitative analysis of their genomic data. Furthermore, it enlightened that ligand binding affinity of sweet/bitter taste molecules in the taste receptors of any proximal pair of organisms would be similar.

genomics↗

bioRxiv2021

An insight into the evolutionary history of Indoplanorbis exustus (Bulinidae: Gastropoda)at the scale of population and species

The history of a lineage is intertwined with the history of the landscape it resides in. Here we showcase how the geo-tectonic and climatic evolution in South Asia and surrounding landmasses have shaped the biogeographic history of Indoplanorbis exustus, a tropical Asian, freshwater, pulmonated snail. We amplified partial COI gene fragment from all over India and combined this with a larger dataset from South and Southeast Asia to carry out phylogenetic reconstruction, species delimitation analysis, and population genetic analyses. Two nuclear genes were also amplified from one individual per putative species to carry out divergence dating and ancestral area reconstruction analyses. The results suggest that Indoplanorbis dispersed out of Africa into India during Eocene. Furthermore, molecular data suggests Indoplanorbis is a species complex consisting of multiple putative species. The primary diversification took place in Northern Indian plains or the Northeast India. The speciation events appear to be primarily allopatric caused by a series of aridification events starting from late Miocene to early Pleistocene. None of the species seemed to have any underlying genetic structure suggestive of high vagility. All the species underwent population fluctuations during the Pleistocene likely driven by the Quaternary climatic fluctuations.

evolutionary biology↗

bioRxiv2021

Cryptic speciation in freshwaters: are speciation in lentic species shaped by paleohydrological events?

The Indian subcontinent is extremely diverse in terms of its flora and fauna. However, there is a severe underestimation of the biotic diversity in invertebrate groups as well as a lack of understanding of the processes generating diversity in these groups. Here we aimed to jointly estimate the cryptic diversity of two freshwater snail species complexes - Pila globosa and Pila virens, and uncover the processes behind the speciation in these groups. We employed phylogenetic, morphometric, population genetic and niche modelling technique to address these questions. We found out that both species complexes consist of several genetically and ecologically distinct putative species. The speciation was primarily driven by allopatric isolation into different river basins. A combination of paleoclimatic and paleohydrological changes during the Miocene have shaped the speciation events. Local climatic adaptation also could have contributed towards some of the speciation events. The study sheds light on the complex interaction between the biology of the species and the environment that shape the diversification patterns in a group.

evolutionary biology↗

bioRxiv2019

Into-India or out-of-India? Historical biogeography of freshwater gastropod genus Pila (Ampullariidae)

The biota of the Indian subcontinent has assembled during various points of the history of its continental drift: some when it was still a part of Gondwanaland and subsequently dispersed out-of-India and some dispersed into-India after it collided with Asia. However, the relative contribution of these connection to the current biotic assembly of the subcontinent is still under-explored. We aimed to understand the relative importance of these various routes of biotic assembly in India through studying the historical biogeography of tropical Old World freshwater snail genus Pila. We reconstructed a near-complete phylogeny of Ampullariidae including all the described Pila species from India and published sequences of Ampullariids from all over the world from two mitochondrial and two nuclear markers. Thereafter molecular dating and ancestral area reconstruction analyses were carried out in order to ascertain the time frame and route of colonization of India. The results suggest that Pila dispersed into India as well as other parts of tropical Asia from Africa after both India and Africa collided with Eurasia. Furthermore, multiple dispersals have taken place between Southeast Asia and India. The findings consolidate the rapidly building evidence that much of the current assemblage of biota actually dispersed into-India after it collided with Asia.

evolutionary biology↗

bioRxiv2018

Role of geography and climatic oscillations in governing into-India dispersal of freshwater snails of the family: Viviparidae

The Indian subcontinent has experienced numerous paleogeological and paleoclimatic events during the Cenozoic which shaped the biotic assembly over time in the subcontinent. The role of these events in governing the biotic exchange between Southeast Asia and Indian subregion is underexplored. We aimed to uncover the effects the collision of the Indian and Asian plate, marine transgression in the Bengal basin as well as the paleoclimatic changes in the subcontinent and adjoining regions, on the dispersal of freshwater snail family Viviparidae from Southeast Asia (SEA) to Indian subregion. Extensive sampling was carried out throughout the Indian subcontinent to capture the current diversity of the targeted lineages. Three mitochondrial and two nuclear markers were sequenced from these samples and combined with published sequences to reconstruct a near complete global phylogeny of Viviparidae. Molecular dating and ancestral range estimation were undertaken to obtain the time frame for the dispersal events. Results from these analyses were contrasted with paleoclimate and paleogeology to better understand the biogeography of Indian viviparids. Results support at least two dispersal events into India from Southeast Asia. The earlier event is likely to have occurred during a warm and humid Eocene period before a permanent land connection was established between the two landmasses. While the more recent dispersal occurred post-suturing and overlapped with a time in late Tertiary to Quaternary when arid climate prevailed. However, we could not firmly establish how the marine transgressions influenced the dispersal events. Even though most biotic exchange between India and SEA are noted to be post-suturing, our results add to a growing body of work that suggests faunal exchange pre-suturing probably mediated by intermittent land connections.

evolutionary biology↗