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Goswami, A.

Publications and source records attributed to Goswami, A..

At least 37 records · Page 2Linked to original sources

Marine phytoplankton and heterotrophic bacteria rapidly adapt to future pCO2 conditions in experimental co-cultures

The CO2 content of Earths atmosphere is rapidly increasing due to human consumption of fossil fuels. Models based on short-term culture experiments predict that major changes will occur in marine phytoplankton communities in the future ocean, but these models rarely consider how the evolutionary potential of phytoplankton or interactions within marine microbial communities may influence these changes. Here we experimentally evolved representatives of four phytoplankton functional types (silicifiers, calcifiers, coastal cyanobacteria, and oligotrophic cyanobacteria) in co-culture with a heterotrophic bacterium, Alteromonas, under either present-day or predicted future pCO2 conditions. Growth rates of cyanobacteria generally increased under both conditions, and the growth defects observed in ancestral Prochlorococcus cultures at elevated pCO2 and in axenic culture were diminished after evolution, possibly due to regulatory mutations in antioxidant genes. Except for Prochlorococcus, mutational profiles suggested phytoplankton experienced primarily purifying selection, but most Alteromonas lineages showed evidence of directional selection, especially when co-cultured with eukaryotic phytoplankton, where evolution appeared to favor a broad metabolic switch from growth on small organic acids to catabolism of more complex carbon substrates. Evolved Alteromonas were also poorer "helpers" for Prochlorococcus, supporting the assertion that the interaction between Prochlorococcus and heterotrophic bacteria is not a true mutualism but rather a competitive interaction stabilized by Black Queen processes. This work provides new insights on how phytoplankton will respond to anthropogenic change and on the evolutionary mechanisms governing the structure and function of marine microbial communities.

evolutionary biology↗

How many specimens make a sufficient training set for automated 3D feature extraction?

Deep learning has emerged as a robust tool for automating feature extraction from 3D images, offering an efficient alternative to labour-intensive and potentially biased manual image segmentation methods. However, there has been limited exploration into the optimal training set sizes, including assessing whether artificial expansion by data augmentation can achieve consistent results in less time and how consistent these benefits are across different types of traits. In this study, we manually segmented 50 planktonic foraminifera specimens from the genus Menardella to determine the minimum number of training images required to produce accurate volumetric and shape data from internal and external structures. The results reveal unsurprisingly that deep learning models improve with a larger number of training images and that data augmentation can enhance network accuracy by up to 8.0%. Notably, predicting both volumetric and shape measurements for the internal structure poses a greater challenge compared to the external structure, due to low contrast between different materials and increased geometric complexity. These results provide novel insight into optimal training set sizes for precise image segmentation of diverse traits and highlight the potential of data augmentation for enhancing multivariate feature extraction from 3D images. Subject CategoryLife Sciences - Computer Science Subject Areascomputational biology, Artificial Intelligence

evolutionary biology↗

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↗

Neither Williston nor Dollo: mandibular complexity from stem tetrapods to modern amphibians

Directional trends in evolution have long captured the attention of biologists, and are particularly interesting when they reflect fundamental developmental processes that underlie morphological change. Here, we apply deep time data and a phylogenetic comparative framework to assess two fundamental "laws" - Willistons law of phenotypic simplification and Dollos law of irreversibility - in the tetrapod mandible, a structure that has sustained the same primary function of feeding for nearly 400 million years. In spite of this conserved function, the tetrapod mandible has undergone numerous morphological and compositional changes during and since the initial water-to-land transition around 390Ma. To quantify these shifts, we reconstructed the compositional ev olution of the mandible with 31 traits scored in 568 species from early tetrapods through to modern amphibians, thereby capturing immense developmental and ecological diversity as well as an excellent fossil record. Mandibular complexity and jaw disparity are highest at the base of the tetrapod tree and generally decrease through time, with stasis dominating over the last ~160M years. Nonetheless, we find a lack of support for Willistons and Dollos laws, with loss and gain of jaw components equally likely throughout the course of early tetrapod and amphibian evolution. Combined, our results demonstrate that evolutionary patterns of mandibular complexity are more nuanced than either Willistons or Dollos laws allow. Thus, laws of simplification are too crude to capture the evolutionary processes underlying the evolution of even a functionally conserved structure through deep time. SummaryThe lower jaw is a key innovation in vertebrate evolution with a unifying primary function: feeding. In spite of this conserved function, the jaw is extremely diverse in shape and composition. In limbed vertebrates (tetrapods), the jaw evolves from a complex structure comprising multiple elements and high numbers of teeth towards a simpler structure comprising few elements and generally fewer teeth. Superficially, this pattern suggests support for both Willistons and Dollos laws of phenotypic simplification and irreversibility, respectively. However, we find a lack of support for either law in the jaw of the earliest tetrapods and amphibians, adding to growing literature refuting overly simplified "laws" governing organismal evolution.

evolutionary biology↗

Structure of puromycin-sensitive aminopeptidase and polyglutamine binding

Puromycin-sensitive aminopeptidase (E.C. 3.4.11.14, UniProt P55786), a zinc metallopeptidase belonging to the M1 family, degrades a number of bioactive peptides as well as peptides released from the proteasome, including polyglutamine. We report the crystal structure of PSA at 2.3 A'. Overall, the enzyme adopts a V-shaped architecture with four domains characteristic of the M1 family aminopeptidases, but it is in a less compact conformation compared to most M1 enzymes of known structure. A microtubule binding sequence is present in a C-terminal HEAT repeat domain of the enzyme in a position where it might serve to mediate interaction with tubulin. In the catalytic metallopeptidase domain, an elongated active site groove lined with aromatic and hydrophobic residues and a large S1 subsite may play a role in broad substrate recognition. The structure with bound polyglutamine shows a possible interacting mode of this peptide, which is supported by mutation.

biochemistry↗

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↗

Ecological and life history drivers of avian skull evolution

One of the most famous examples of adaptive radiation is that of the Galapagos finches, where skull morphology, particularly the beak, varies with feeding ecology. Yet increasingly studies are questioning the strength of this correlation between feeding ecology and morphology in relation to the entire neornithine radiation, suggesting that other factors also significantly affect skull evolution. Here, we broaden this debate to assess the influence of a range of ecological and life history factors, specifically habitat density, migration, and developmental mode, in shaping avian skull evolution. Using 3D geometric morphometric data to robustly quantify skull shape for 354 extant species spanning avian diversity, we fitted flexible phylogenetic regressions and estimated evolutionary rates for each of these factors across the full dataset. The results support a highly significant relationship between skull shape and both habitat density and migration, but not developmental mode. We further found heterogenous rates of evolution between different character states within habitat density, migration, and developmental mode, with rapid skull evolution in species which occupy dense habitats, are migratory, or are precocial. These patterns demonstrate that diverse factors impact the tempo and mode of avian phenotypic evolution, and that skull evolution in birds is not simply a reflection of feeding ecology. Impact summaryAlmost 200 years ago, Darwin found that the beaks of Galapagos finches were different shapes in birds with different diets. Nowadays, it is well established that phylogeny, allometry, and ecology can also be key factors in shaping skulls. Yet, the influence of specific aspects of ecology, as well as life history, on morphological evolution remain poorly constrained. Here, we examined whether three novel factors also influence the shape of bird skulls and rates of evolution: habitat density, migration, or developmental mode. To do so, we combine high resolution 3D quantification of skull shape with dense taxonomic sampling across living birds. Our analyses revealed that skull shape varies in birds based on the density of vegetation in their habitats and on the extent to which they migrate. However, how independent birds are when they are born does not appear to influence overall skull shape. Despite these differences in how much they influence the shape of the skull, habitat density, migration and life history all influence the rate at which bird skulls evolve. Birds evolved fastest if they live in densely vegetated habitats, migrate long distances, or are precocial. These results add to the growing body of evidence that skull evolution in birds is impacted by a diverse range of factors, and suggests that habitat density, migration and life history should be considered in future analyses on drivers of phenotypic evolution.

evolutionary biology↗

How to tuna fish: constraint, convergence and integration in the neurocranium of pelagiarian fishes.

Morphological evolution of the vertebrate skull has been explored across a wide range of tetrapod clades, but teleost fishes, accounting for roughly half of all vertebrate species, have largely been overlooked. Here we present the results of a study investigating three-dimensional morphological evolution across 114 species of Pelagiaria, a morphologically diverse clade of open-ocean teleost fishes that includes tuna and mackerel. Despite showing high shape disparity, the majority of taxa are concentrated in fairly restricted regions of morphospace, with taxa from all families falling into three distinct clusters. Phylogenetic signal in shape data is significant but low (Kmult = 0.27, p = 0.001) and a single-rate Ornstein-Uhlenbeck model of evolution is supported, revealing convergence in shape within and between families. Shape is significantly correlated with body elongation (R2 = 0.35, p =0.001), but correlation with size, diet, and habitat depth is weak. Integration of the neurocranium is high, supporting the hypothesis that high integration may promote the evolution of more extreme morphologies. Taken together, these results suggest that shape evolution in the pelagiarian neurocranium is constrained by a number of factors, resulting in the repeated evolution of a restricted range of morphologies.

evolutionary biology↗

Testing heterochrony: Connecting skull shape ontogeny and evolution of feeding adaptations in baleen whales

Ontogeny plays a key role in the evolution of organisms, as changes during the complex processes of development can allow for new traits to arise. Identifying changes in ontogenetic allometry - the relationship between skull shape and size during growth - can reveal the processes underlying major evolutionary transformations. Baleen whales (Mysticeti, Cetacea) underwent major morphological changes in transitioning from their ancestral raptorial feeding mode to the three specialised filter feeding modes observed in extant taxa. Heterochronic processes have been implicated in the evolution of these feeding modes, and their associated specialised cranial morphologies, but their role has never been tested with quantitative data. Here, we quantified skull shapes ontogeny and reconstructed ancestral allometric trajectories using 3D geometric morphometrics and phylogenetic comparative methods on sample representing modern mysticetes diversity. Our results demonstrate that Mysticeti, while having a common developmental trajectory, present distinct cranial shapes from early in their ontogeny corresponding to their different feeding ecologies. Size is the main driver of shape disparity across mysticetes. Disparate heterochronic processes are evident in the evolution of the group: skim feeders present accelerated growth relative to the ancestral nodes, while Balaenopteridae have overall slower growth, or paedomorphosis. The grey whale is the only taxon with a relatively faster rate of growth in this group, which might be connected to its unique benthic feeding strategy. Reconstructed ancestral allometries and related skull shapes indicate that extinct taxa used less specialized filter feeding modes, a finding broadly in line with the available fossil evidence.

evolutionary biology↗

De novo design of anti-variant COVID vaccine with T-cell memory

Recent studies have shown the efficacy of hybrid SARS-COV-2 vaccines using wild-type nucleocapsid (N) and Spike (S) protein. We upgraded this strategy one step further using clinically proven spike protein by considering the delta and post-delta omicron variant of concern (VOC) mutations and nucleocapsid peptides conferring T-cell immunity. Nucleocapsid peptides are considered much better immunological replacement of nucleocapsid proteins. Hence, peptide linking strategy is applied which is more economic for cellular biosynthesis than whole proteins. An envelope peptide with potent T-cell immune response is also selected. All these peptides are clustered in this hybrid spikes designed cytoplasmic region separated by non-immunogenic helical linkers. The resulting domain is more folded in the construct devoid of transmembrane domain after AlphaFold analysis. Alongside, we also propose the idea of introduction of any T-cell peptide like other Human Corona Viruses (HuCoV) in these linker regions whenever required. In addition to SARS-COV-2, the same approach can be applied for any emergency or even long-term unsolved outbreaks of Influenza, Dengue and West Nile Virus etc. In this era of novelty as presented by subunit and nucleic acid vaccines, multiepitope strategies like this can help to combat multiple diseases successfully in real time to give hope for better future.

bioinformatics↗

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↗

Accountable Prediction of Drug ADMET Properties with Molecular Descriptors

Drugs are chemical substances of low molecular weights that require to travel from the site of administration to the site of action. For safety and effective permeability, drugs are required to exhibit ideal absorption, distribution, metabolism, excretion and toxicity (ADMET) properties. Given the Simplified Molecular Input Line Entry System (SMILES) representation of drugs, we aim to predict their ADMET properties. By feeding molecular descriptors (as global features) to traditional machine learning models, we show that ADMET properties of drug molecules can be predicted with an accuracy competitive with the state-of-the-art deep learning models. We demonstrate that the proposed approach with only 31 molecular descriptors beats the state-of-the-art for 3 datasets. Moreover, it stands the second best for 2 other datasets, where none of the best provides a statistically significant improvement. We also demonstrate that two-dimensional descriptors can better represent absorption, distribution and excretion properties than the fingerprints widely used in the literature. However, they fail to distinguish metabolism and toxicity properties.

bioinformatics↗

The ontogeny of asymmetry in echolocating whales

Extreme asymmetry of the skull is one of the most distinctive traits that characterizes toothed whales (Odontoceti, Cetacea). The origin and function of cranial asymmetry are connected to the evolution of echolocation, the ability to use high frequency sounds to navigate the surrounding environment. Although this novel phenotype must arise through changes in cranial development, the ontogeny of cetacean asymmetry has never been investigated. Here we use three-dimensional geometric morphometric to quantify the changes in degree of asymmetry and skull shape during prenatal and postnatal ontogeny for five genera spanning odontocete diversity (oceanic dolphins, porpoises, and beluga). Asymmetry in early ontogeny starts low and tracks phylogenetic relatedness of taxa. Distantly-related taxa that share aspects of their ecology overwrite these initial differences via heterochronic shifts, ultimately converging on comparable high levels of skull asymmetry. Porpoises maintain low levels of asymmetry into maturity and present a decelerated rate of growth, likely retained from the ancestral condition. Ancestral state reconstruction of allometric trajectories demonstrates that both paedomorphism and peramorphism contribute to cranial shape diversity across odontocetes. This study provides a striking example of how divergent developmental pathways can produce convergent ecological adaptations, even for some of the most unusual phenotypes exhibited among vertebrates.

evolutionary biology↗

Immunomodulatory effect of mycobacterial outer membrane vesicles coated nanoparticles

Tuberculosis (TB) is one of the most widely prevalent infectious diseases that cause significant mortality. Bacillus Calmette-Guerin (BCG), the current TB vaccine used in clinics, shows variable efficacy and has safety concerns for immunocompromised patients. There is a need to develop new and more effective TB vaccines. Outer membrane vesicles (OMVs) are vesicles released by Mycobacteria that contain several lipids and membrane proteins and act as a good source of antigens to prime immune response. However, the use of OMVs as vaccines has been hampered by their heterogeneous size and low stability. Here we report that mycobacterial OMVs can be stabilized by coating over uniform-sized 50 nm gold nanoparticles. The OMV-coated gold nanoparticles (OMV-AuNP) show enhanced uptake and activation of macrophages and dendritic cells. Proteinase K and TLR inhibitor studies demonstrated that the enhanced activation was attributed to proteins present on OMVs and was mediated primarily by TLR2 and TLR4. Mass spectrometry analysis revealed several potential membrane proteins that were common in both free OMVs and OMV-AuNP. Such strategies may open up new avenues and the utilization of novel antigens for developing TB vaccines.

bioengineering↗

Heavy metal pollution impacts soil bacterial community structure and antimicrobial resistance at the Birmingham 35th Avenue Superfund Site

Heavy metals (HMs) are known to modify bacterial communities both in the laboratory and in situ. As a consequence, soils in HM contaminated sites like the U.S. Environmental Protection Agency (EPA) Superfund sites are predicted to have altered ecosystem functioning, with potential ramifications for the health of organisms, including humans, that live nearby. Further, several studies have shown that metal tolerant bacteria are often also resistant to antimicrobial agents (AMR), and therefore HM contaminated soils could potentially act as reservoirs that could disseminate AMR genes into human-associated pathogenic bacteria. To explore this possibility soil samples were collected from six public locations in the zip code 35207 (the home of the North Birmingham 35th Avenue Superfund site) and in six public areas in a neighboring reference zip code (35214). Sequencing of the V4 region of the bacterial 16S rRNA gene revealed that elevated concentrations of HMs As, Mn, Pb, and Zn reduced microbial diversity and altered community structure within each zip code. While there was no difference between zip codes in the proportion of total culturable microbes that survived antimicrobial or metal exposure, bacterial isolates with HMR almost always also exhibited AMR. Metagenomes inferred using PICRUST2 also predicted significantly higher mean relative frequencies in 35207 for several AMR genes related to both specific and broad-spectrum AMR phenotypes. Together, these results support the hypothesis that chronic HM pollution alters soil bacterial community structure in ecologically meaningful ways and may also select for bacteria with increased potential to contribute to AMR in human bacterial disease.

microbiology↗

Cationic inhalable particles for enhanced drug delivery to M. tuberculosis infected macrophages

Inhalable microparticle-based drug delivery platforms are being investigated extensively for Tuberculosis (TB) treatment as they offer efficient deposition in lungs and improved pharmacokinetics of the encapsulated cargo. However, the effect of physical parameters of microcarriers on interaction with Mycobacterium tuberculosis (Mtb) infected mammalian cells is underexplored. In this study, we report that Mtb-infected macrophages are highly phagocytic and microparticle surface charge plays a major role in particle internalization by infected cells. Microparticles of different sizes (0.5 - 2 m) were internalized in large numbers by Mtb-infected THP-1 macrophages and murine primary Bone Marrow Derived Macrophages in vitro. Drastic improvement in particle uptake was observed with cationic particles in vitro and in mice lungs. Rapid uptake of rifampicin-loaded cationic microparticles allowed high intracellular accumulation of the drug and lead to enhanced anti-bacterial function when compared to non-modified rifampicin-loaded microparticles. Cytocompatibility assay and histological analysis in vivo confirmed that the formulations were safe and did not elicit any adverse reaction. Additionally, pulmonary delivery of cationic particles in mice resulted in two-fold higher uptake in resident alveolar macrophages compared to non-modified particles. This study provides a framework for future design of drug carriers to improve delivery of anti-TB drugs inside Mtb-infected cells.

bioengineering↗

Leishmania Hijacks microRNA Import-Export Machinery of Infected Macrophage and Survives by Cross-Communicating Host miR-146a to Subjugate HuR and miR-122 in Neighbouring cells

Leishmania donovani, the causative agent of visceral leishmaniasis, infects and resides within tissue macrophage cells of the mammalian host. It is not clear how the parasite infected cells cross-talk with the non-infected cells in the infection niche to regulate the infection process. Interestingly, miRNAs, the regulatory small RNAs of the host, could get trafficked into and out of infected cells as part of extracellular vesicles to ensure exchange of the epigenetic signals and can regulate the expression of their target genes in both donor and recipient cells. Leishmania, for its survival in host macrophage, adopts a dual strategy to regulate the intercellular transport of host miRNAs. The parasite, by preventing mitochondrial function of the host cells, restricts the entry of liver cell derived miR-122 containing extracellular vesicles in infected macrophage to curtail the inflammatory response by miR-122. The parasite reciprocally upregulates the extracellular export of anti-inflammatory miR-146a from the infected cells. The exported miR-146a restricts miR-122 production in liver cells and polarizes neighbouring naive macrophages to the M2 state. miR-146a upregulates IL-10 in neighbouring macrophages where miR-146a dominates the RNA binding and miRNA suppressor protein HuR to inhibit the expression of proinflammatory cytokine mRNAs having HuR-interacting AU-rich elements and polarized the recipient cells to M2 stage. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=116 SRC="FIGDIR/small/459146v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@32e32dorg.highwire.dtl.DTLVardef@e0d3c6org.highwire.dtl.DTLVardef@6f77e6org.highwire.dtl.DTLVardef@289e49_HPS_FORMAT_FIGEXP M_FIG C_FIG Key FindingsO_LILeishmania stops vesicular entry of inflammatory miR-122 in infected cells by causing mitochondrial depolarization C_LIO_LILeishmania secrets miR-146a from infected cells to stop miR-122 production in neighbouring hepatocytes C_LIO_LImiR-146a containing vesicles secreted by infected cells stops inflammatory response in recipient naive macrophage C_LIO_LImiR-146 targets RNA binding protein HuR to stop inflammatory cytokine production C_LI

immunology↗

Testing hypotheses of marsupial brain size variation using phylogenetic multiple imputations and a Bayesian comparative framework

Considerable controversy exists about which hypotheses and variables best explain mammalian brain size variation. We use a new, high-coverage dataset of marsupial brain and body sizes, and the first phylogenetically imputed full datasets of 16 predictor variables, to model the prevalent hypotheses explaining brain size evolution using phylogenetically corrected Bayesian generalised linear mixed-effects modelling. Despite this comprehensive analysis, litter size emerges as the only significant predictor. Marsupials differ from the more frequently studied placentals in displaying much lower diversity of reproductive traits, which are known to interact extensively with many behavioural and ecological predictors of brain size. Our results therefore suggest that studies of relative brain size evolution in placental mammals may require targeted co-analysis or adjustment of reproductive parameters like litter size, weaning age, or gestation length. This supports suggestions that significant associations between behavioural or ecological variables with relative brain size may be due to a confounding influence of the extensive reproductive diversity of placental mammals.

evolutionary biology↗