Biology subjects

Davalos, L. M.

Publications and source records attributed to Davalos, L. M..

14 recordsLinked to original sources

bioRxiv2026

Integrated genomics and transcriptomics reveal mechanisms of extreme dietary adaptation in vampire bats

Vampire bats are the only tetrapods that feed exclusively on blood. To uncover the molecular basis of this extreme dietary specialization, we generated six new reference genomes, including genomes of all three vampire bat species, and integrated comparative analyses of gene sequence evolution (selection signatures, duplications, and losses) with transcriptomic data from six major organs to identify shifts in gene expression. Our integrative analyses reveal sequence or expression changes in 150 genes that illuminate the genetic mechanisms underlying sanguivory. Through comparative analyses and experiments, we show that the enlarged vampire bat stomach has increased connective tissue content enabling extreme expansion, is pH-neutral, and exhibits reduced mucus production, together providing molecular insights into its shift from a digestive to an absorptive organ for water, electrolytes, and vitamins. We further uncover pathway-level molecular changes underlying altered gastrointestinal motility; trypsin-dependent protein digestion; upregulated amino acid catabolism with key aspects diverging from other mammals; impaired dietary fat digestion counterbalanced by increased fatty acid synthesis; defective sugar metabolism and natural insulin deficiency; enhanced heme iron absorption; and adult splenic erythropoiesis. Together, these findings reveal the molecular adaptations that enable one of the most extreme dietary transitions among vertebrates.

evolutionary biology↗

bioRxiv2026

Pathogenesis and host response to a novel Tacaribe virus isolate in experimentally-infected Jamaican fruit bats

Tacaribe virus (TCRV) was the first arenavirus discovered in the New World and was isolated from Artibeus bats in Trinidad and Tobago in the 1950s. One isolate, TRVL-11573, remains but it was passaged by intracranial inoculation of newborn mice 22 times that likely changed its biology. This isolate has been extensively used for arenavirus research, including our previous work that showed it can cause fatal neurological disease in Jamaican fruit bats (Artibeus jamaicensis). Another divergent TCRV, DOM2014, was recently identified in transcriptome data from a Jamaican fruit bat captured in the Dominican Republic that contained TCRV genome. A kidney fragment homogenate from this bat was inoculated into Jamaican fruit bats and all became infected with signs of mild liver disease. Experimental challenge of Jamaican fruit bats with DOM2014 led to nonfatal infection that persisted through the end of the study on day 21 and with contact transmission to naive bats. Histopathology, immunohistochemistry and serum chemistry confirmed infection and mild liver disease, but none of the bats produced neutralizing antibodies. B cell receptor transcripts suggested limited somatic hypermutation that could explain the lack of detectable neutralizing antibodies. Transcriptome profiling of livers and spleens showed signatures of a typical innate antiviral response; however, evidence of adaptive immune suppression was also present. Similarly, liver transcriptome analysis showed signatures of an expected innate antiviral response and metabolic dysfunction. The isolation of TCRV DOM2014 provides a relevant model for the study of a bat reservoir host, and which may challenge the extensive work previously conducted with TRVL-11573. IMPORTANCESeveral New World arenaviruses cause disease in humans and many are BSL-4 agents. TCRV strain TRVL-11573 has been used since the 1950s to study arenavirus biology; however, because it was intracranially passaged in newborn mice and Vero cells, it likely accumulated mutations that changed its biology. This assertion has been reinforced in recent years with discovery of divergent TCRV sequences in wild Artibeus bats that are substantially different than TRVL-11573, thus the prototype strain is unlikely to represent wildtype TCRV. The isolation of a new TCRV strain that has retained its genome fidelity allows a better understanding of TCRVs biology and pathogenic potential. The availability of pathogen-free Jamaican fruit bats and cell lines that are permissive for TCRV DOM2014 will also help retain the biological features of the virus. Collectively, this is among the most tractable bat reservoir host models developed and provides a system for dissection of how bats host viruses. Moreover, it may be a suitable model for the study of therapeutics and vaccines for New World arenaviruses.

microbiology↗

bioRxiv2026

Exon Targeted Retrieval and Classification Toolbox (ExTRaCT): a gene search pipeline to find APOBEC3 Z-domains in novel bat genomes

MotivationSeveral computation gene search tools exist to identify and annotate an ever-growing body of newly sequenced genomes of different species. Many annotation tools, however, fall short when the target species diverges from well-studied model organisms, and when searching for short genes with multiple copies. ResultsWe have developed the Exon Targeted Retrieval and Classification Toolbox, ExTRaCT, an automated pipeline to identify any gene exon with conserved structure in novel species genome assemblies. In the use cases presented here, we applied our search tool to 102 bat genomes to find APOBEC3 gene family members. We show that our homolog search algorithm is efficient (run time average of 5 hours for over 100 genomes), works well with reference sequences distantly related to the target (1 out of 498 misclassifications, 0 false positives and 2 false negatives), and is easy to use. As genomic sequencing becomes faster and more accessible, ExTRaCT has downstream applications in phylogenetic, biochemical and genomic studies. It is a simple computational tool that provides a solution to target gene identification, requiring neither whole-genome-assembly annotations, nor prior knowledge of closely related species. Availabilityhttps://doi.org/10.5281/zenodo.15769018 ContactBrenda.delamonica@stonybrook.edu Supplementary informationSupplementary data are available at Bioinformatics online.

genomics↗

bioRxiv2025

Developmental bias explains the evolutionary trend towards simple leaf shapes

The relative influence of developmental bias and natural selection on evolutionary outcomes remains a central, unresolved question in evolutionary biology. Here, we combine large-scale phylogenetic trees with herbarium data to confirm that, across the evolutionary history of angiosperms, transitions from complex to simple leaf shapes have occurred at a significantly higher rate than the reverse. To investigate whether this directional trend reflects an underlying developmental bias, we simulate evolutionary transitions by introducing random mutations into a well-established computational model of leaf development. Despite excluding selection, the transition rates produced by the model closely align with those observed in the phylogenetic data. This agreement indicates that a strong developmental bias, reflecting the relative ease with which gene regulatory networks generate simple over complex leaves, has played a major role in shaping the evolution of leaf morphology. Our findings echo recent work showing that similar biases towards simplicity influence the evolution of molecular structures, including RNA secondary structures and protein quaternary assemblies. Together, these results suggest that a developmental bias favouring simplicity may be a widespread and general feature of evolutionary systems.

evolutionary biology↗

bioRxiv2025

Seasonal brain regeneration and chromosome instability are linked to selection on DNA repair in Sorex araneus

Sorex araneus, the Eurasian common shrew, has seasonal brain size plasticity (Dehnels phenomenon) and abundant intraspecific chromosomal rearrangements, but genomic contributions to these traits remain unknown. We couple a chromosome-scale genome assembly with seasonal brain transcriptomes to discover relationships between molecular changes and both traits. Positively selected genes enriched the Fanconi anemia DNA repair pathway, which prevents the accumulation of chromosomal aberrations, and is likely involved in chromosomal rearrangements (FANCI, FAAP100). Genes involved in neurogenesis show either signatures of positive selection (PCDHA6), seasonal differential expression in the cortex and hippocampus (Notch signaling), or both (SOX9), suggesting a role for cellular proliferation in seasonal brain shrinkage and regrowth. Both positive selection and evolutionary upregulation in the shrew hypothalamus of VEGFA and SPHK2 indicate adaptations in hypothalamic metabolic homeostasis have evolved together with Dehnels phenomenon. These findings reveal genomic changes central to the evolution of both chromosomal instability and cyclical patterns in brain gene expression that characterizes mammalian brain size plasticity. TeaserGenomic and expression variations are key to chromosomal instability and seasonal brain plasticity in the common shrew.

evolutionary biology↗

bioRxiv2024

Human and bats genome robustness under COSMIC mutational signatures

Carcinogenesis is an evolutionary process, and mutations can fix the selected phenotypes in selective microenvironments. Both normal and neoplastic cells are robust to the mutational stressors in the microenvironment to the extent that secure their fitness. To test the robustness of genes under a range of mutagens, we developed a sequential mutation simulator, Sinabro, to simulate single base substitution under a given mutational process. Then, we developed a pipeline to measure the robustness of genes and cells under those mutagenesis processes. We discovered significant human genome robustness to the APOBEC mutational signature SBS2, which is associated with viral defense mechanisms and is implicated in cancer. Robustness evaluations across over 70,000 sequences against 41 signatures showed higher resilience under signatures predominantly causing C-to-T (G-to-A) mutations. Principal component analysis indicates the GC content at the codons wobble position significantly influences robustness, with increased resilience noted under transition mutations compared to transversions. Then, we tested our results in bats at extremes of the lifespan-to-mass relationship and found the long-lived bat is more robust to APOBEC than the short-lived one. By revealing robustness to APOBEC ranked highest in human (and bats with much more than number of APOBEC) genome, this work bolsters the key potential role of APOBECs in aging and cancer, as well as evolved countermeasures to this innate mutagenic process. It also provides the baseline of the human and bat genome robustness under mutational processes associated with aging and cancer. HighlightsO_LISinabro, the sequential mutation simulator, facilitates measuring the robustness of human protein-coding sequences under all COSMIC mutational signatures. C_LIO_LIRobustness under APOBEC mutational signatures showed the largest mean and standard deviation in the human genome. C_LIO_LIRobustness to mutational signatures analysis reveals the role of APOBECs is complementary to cancer in the evolvability of cancer cells in later stages. C_LIO_LIPrincipal component analysis indicates that the GC content at the codons wobble position significantly influences robustness. C_LIO_LIA long-lived bat (Myotis myotis) has higher robustness to APOBECs than a short-lived one (Molossus molossus) than humans. C_LI

genomics↗

bioRxiv2024

Seasonal and comparative evidence of adaptive gene expression in mammalian brain size plasticity

Contrasting almost all other mammalian wintering strategies, Eurasian common shrews, Sorex araneus, endure winter by shrinking their brain, skull, and most organs, only to then regrow to breeding size the following spring. How such tiny mammals achieve this unique brain size plasticity while maintaining activity through the winter remains unknown. To discover potential adaptations underlying this trait, we analyzed seasonal differential expression in the shrew hypothalamus, a brain region that both regulates metabolic homeostasis and drastically changes size, and compared hypothalamus expression across species. We discovered seasonal variation in suites of genes involved in energy homeostasis and apoptosis, shrew-specific upregulation of genes involved in the development of the hypothalamic blood brain barrier and calcium signaling, as well as overlapping seasonal and comparative gene expression divergence in genes implicated in the development and progression of human neurological and metabolic disorders, including CCDC22. With high metabolic rates and facing harsh winter conditions, Sorex araneus have evolved both adaptive and plastic mechanisms to sense and regulate their energy budget. Many of these expression changes mirrored those identified in human neurological and metabolic disease, highlighting the interactions between metabolic homeostasis, brain size plasticity, and longevity.

evolutionary biology↗

bioRxiv2024

Testing for reciprocal trait influence in plant-frugivore interactions using generalized joint attribute modeling

Under an adaptive hypothesis, the reciprocal influence between mutualistic plants and frugivores is expected to result in dispersal syndromes comprising both frugivore and plant traits that structure fruit consumption. Tests of this adaptive hypothesis, however, focus on traits of either fruits or frugivores but not both and often ignore within-species variation. To overcome these limitations, we analyze traits for the mutualistic ecological network comprising Carollia bats that feed on and disperse Piper seeds. For these analyses, we use generalized joint attribute modeling (GJAM), a Bayesian modeling approach that simultaneously accounts for multiple sources of variance across trait types. In support of the adaptive hypothesis and indicating niche partitioning among Carollia bats, we find differential consumption of a suite of Piper species influenced by bat traits such as body size; however, Piper morphological traits had no effect on bat consumption. Slow evolutionary rates, dispersal by other vertebrates, and unexamined fruit traits, such as Piper chemical bouquets, may explain the lack of association between bat Piper consumption and fruit morphological traits. We have identified a potential asymmetric influence of frugivore traits on plant-frugivore interactions, providing a template for future trait analyses of plant-animal networks.

ecology↗

bioRxiv2023

Large captivity effect based on gene expression comparisons between captive and wild shrew brains

Compared to their free-ranging counterparts, wild animals in captivity experience different conditions with lasting physiological and behavioral effects. Although shifts in gene expression are expected to occur upstream of these phenotypes, we found no previous gene expression comparisons of captive vs. free-ranging mammals. We assessed gene expression profiles of three brain regions (cortex, olfactory bulb, and hippocampus) of wild shrews (Sorex araneus) compared to shrews kept in captivity for two months and undertook sample drop-out to examine robustness given limited sample sizes. Consistent with captivity effects, we found hundreds of differentially expressed genes in all three brain regions, 104 overlapping across all three, that enriched pathways associated with neurodegenerative disease, oxidative phosphorylation, and genes encoding ribosomal proteins. In the shrew, transcriptomic changes detected under captivity resemble responses in several human pathologies, including major depressive disorder and neurodegeneration. While interpretations of individual genes are tempered by small sample sizes, we propose captivity influences brain gene expression and function and can confound analyses of natural processes in wild individuals under captive conditions.

genetics↗

bioRxiv2023

Chiropterans are a hotspot for horizontal transfer of DNA transposons in Mammalia

Horizontal transfer of transposable elements is an important mechanism contributing to genetic diversity and innovation. Bats (order Chiroptera) have repeatedly been shown to experience horizontal transfer of transposable elements at what appears to be a high rate compared to other mammals. We investigated the occurrence of horizontally transferred DNA transposons involving bats. We found over 200 putative horizontally transferred elements within bats; sixteen transposons were shared across distantly related mammalian clades and two other elements were shared with a fish and two lizard species. Our results indicate that bats are a hotspot for horizontal transfer of DNA transposons. These events broadly coincide with the diversification of several bat clades, supporting the hypothesis that DNA transposon invasions have contributed to genetic diversification of bats.

molecular biology↗

bioRxiv2022

Insights into mammalian TE diversity via the curation of 248 mammalian genome assemblies

We examined transposable element (TE) content of 248 placental mammal genome assemblies, the largest de novo TE curation effort in eukaryotes to date. We find that while mammals resemble one another in total TE content and diversity, they show substantial differences with regard to recent TE accumulation. This includes multiple recent expansion and quiescence events across the mammalian tree. Young TEs, particularly LINEs, drive increases in genome size while DNA transposons are associated with smaller genomes. Mammals tend to accumulate only a few types of TE at any given time, with one TE type dominating. We also found association between dietary habit and the presence of DNA transposon invasions. These detailed annotations will serve as a benchmark for future comparative TE analyses among placental mammals. One-Sentence SummaryA de novo assessment of TE content in 248 mammals finds informative trends in mammalian genome evolution.

genomics↗

bioRxiv2021

Diversity in olfactory receptor repertoires is associated with dietary specialization in a genus of frugivorous bat

Mammalian olfactory receptors (ORs) are a diverse family of genes encoding proteins that directly interact with environmental chemical cues. ORs evolve via gene duplication in a birth-death fashion, neofunctionalizing and pseudogenizing over time. Olfaction is a primary sense used for food detection in plant-visiting bats, but the relationship between dietary specialization and OR repertoires is unclear. Within neotropical Leaf-nosed bats (Phyllostomidae), many lineages are plant specialists, and some have a distinct OR repertoire compared to insectivorous species. Yet, whether specialization on particular plant genera is associated with the evolution of more specialized OR repertoires has never been tested. Using targeted sequence capture, we sequenced the OR repertoires of three sympatric species of short-tailed leaf-nosed bats (Carollia), which vary in their degree of specialization on the fruits of Piper plants. We characterized orthologous versus duplicated receptors among Carollia species, and identified orthologous receptors and associated paralogs to explore the diversity and redundancy of the receptor gene repertoire. The most dedicated Piper specialist, Carollia castanea, had lower OR diversity compared to the two more generalist species (sowelli, perspicillata), but we discovered a few unique sets of ORs within C. castanea with exceptional redundancy of similar gene duplicates. These unique receptors potentially enable C. castanea to detect Piper fruit odorants to an extent that the other species cannot. C. perspicillata, the species with the most generalist diet, had a larger diversity of functional receptors, suggesting the ability to detect a wider range of odorant molecules. The variation among ORs may be a factor in the coexistence of these sympatric species, facilitating the exploitation of different plant resources. Our study sheds light on how gene duplication plays a role in dietary adaptations and underlies patterns of ecological interactions between bats and plants. Impact Statement--though it asks for 3-4 sentencesThe sense of smell is essential to how many animals detect food, yet few studies have demonstrated how dietary evolution has shaped olfactory receptor genes, which encode proteins that bind to environmental scent cues, including food odorants. We compared the evolutionary history of olfactory receptor repertoires in three co-occurring neotropical bat species along a spectrum of dietary specialization on the fruits of Piper plants. We found the more generalist species possessed a more diverse olfactory receptor profile, potentially reflecting an ability to detect more diverse arrays of fruit scent compounds, while the specialist had a narrower profile that demonstrated more redundancy. By introducing creative approaches to measure diversity in large gene families and connecting diet specialization and molecular diversity, this study makes an unprecedented contribution to evolutionary biology.

evolutionary biology↗

bioRxiv2020

Species tree disequilibrium positively misleads models of gene family evolution

Gene duplication is a key source of evolutionary innovation, and multigene families evolve in a birth-death process, continuously duplicating and pseudogenizing through time. To empirically test hypotheses about adaptive expansion and contraction of multigene families across species, models infer gene gain and loss in light of speciation events and these inferred gene family expansions may lead to interpretations of adaptations in particular lineages. While the relative abundance of a gene subfamily in the subgenome may reflect its functional importance, tests based on this expectation can be confounded by the complex relationship between the birth-death process of gene subfamily evolution and the species phylogeny. Using simulations, we confirmed tree heterogeneity as a confounding factor in inferring multi-gene adaptation, causing spurious associations between shifts in birth-death rate and lineages with higher branching rates. We then used the olfactory receptor (OR) repertoire, the largest gene family in the mammalian genome, of different bat species with divergent diets to test whether expansions in olfactory receptors are associated with shifts to frugivorous diets. After accounting for tree heterogeneity, we robustly inferred that certain OR subfamilies exhibited expansions associated with dietary shifts to frugivory. Taken together, these results suggest ecological correlates of individual OR gene subfamilies can be identified, setting the stage for detailed inquiry into within-subfamily functional differences.

evolutionary biology↗

bioRxiv2019

Six new reference-quality bat genomes illuminate the molecular basis and evolution of bat adaptations

Bats account for ~20% of all extant mammal species and are considered exceptional given their extraordinary adaptations, including biosonar, true flight, extreme longevity, and unparalleled immune systems. To understand these adaptations, we generated reference-quality genomes of six species representing the key divergent lineages. We assembled these genomes with a novel pipeline incorporating state-of-the-art long-read and long-range sequencing and assembly techniques. The genomes were annotated using a maximal evidence approach, de novo predictions, protein/mRNA alignments, Iso-seq long read and RNA-seq short read transcripts, and gene projections from our new TOGA pipeline, retrieving virtually all (>99%) mammalian BUSCO genes. Phylogenetic analyses of 12,931 protein coding-genes and 10,857 conserved non-coding elements identified across 48 mammalian genomes helped to resolve bats closest extant relatives within Laurasiatheria, supporting a basal position for bats within Scrotifera. Genome-wide screens along the bat ancestral branch revealed (a) selection on hearing-involved genes (e.g LRP2, SERPINB6, TJP2), which suggest that laryngeal echolocation is a shared ancestral trait of bats; (b) selection (e.g INAVA, CXCL13, NPSR1) and loss of immunity related proteins (e.g. LRRC70, IL36G), including pro-inflammatory NF-kB signalling; and (c) expansion of the APOBEC family, associated with restricting viral infection, transposon activity and interferon signalling. We also identified unique integrated viruses, indicating that bats have a history of tolerating viral pathogens, lethal to other mammal species. Non-coding RNA analyses identified variant and novel microRNAs, revealing regulatory relationships that may contribute to phenotypic diversity in bats. Together, our reference-quality genomes, high-quality annotations, genome-wide screens and in-vitro tests revealed previously unknown genomic adaptations in bats that may explain their extraordinary traits.

genomics↗