Biology subjects

Davalos, L.

Publications and source records attributed to Davalos, L..

9 recordsLinked to original sources

bioRxiv2025

Gene expression reveals the pancreas of Aselli as a critical organ for plasma cell differentiation in the common shrew

Almost all mammals rely on the thymus and bone marrow to generate and differentiate B- and T cells essential for adaptive immunity. A few members of the family Soricidae, or true shrews, have also evolved the pancreas of Aselli, a kidney-sized organ hypothesized to serve this primary immune role, and whose gene expression profile is unknown. Here we introduce transcriptomes of juvenile Sorex araneus pancreas of Aselli, compare them to those of the spleen and chick bursa of Fabricius, an analogous and bird-specific organ, and explore differential expression overlaps with positively selected genes. While differential gene expression analyses revealed overexpression of genes that regulate the differentiation of B cells into long-term plasma cells (e.g., IRF4, XBP1, PRDM1) compared to the spleen and more convergent expression with the bursa of Fabricius than expected by chance (including IRF4), overlaps with positive selection were as expected and included PTPRCAP, which regulates both T and B cell antigen responses and lymph node size. Our results support the specialized role of the pancreas of Aselli in adaptive immunity, and we propose this unique organ evolved at the intersection between extreme metabolic demands and high parasite burdens in tiny yet very active shrews.

evolutionary biology↗

bioRxiv2023

Molecular mechanisms of seasonal brain shrinkage and regrowth inSorex araneus

To meet the challenge of wintering in place many high-latitude small mammals reduce energy demands through hibernation. In contrast, short-lived Eurasian common shrews, Sorex araneus, remain active and shrink, including energy-intensive organs in winter, regrowing in spring in an evolved strategy called Dehnels phenomenon. How this size change is linked to metabolic and regulatory changes to sustain their high metabolism is unknown. We analyzed metabolic, proteomic, and gene expression profiles spanning the entirety of Dehnels seasonal cycle in wild shrews. We show regulatory changes to oxidative phosphorylation and increased fatty acid metabolism during autumn-to-winter shrinkage, as previously found in hibernating species. But in shrews we also found upregulated winter expression of genes involved in gluconeogenesis: the biosynthesis of glucose from non-carbohydrate substrates. Co-expression models revealed changes in size and metabolic gene expression interconnect via FOXO signaling, whose overexpression reduces size and extends lifespan in many model organisms. We propose that while shifts in gluconeogenesis meet the challenge posed by high metabolic rate and active winter lifestyle, FOXO signaling is central to Dehnels phenomenon, with spring downregulation limiting lifespan in these shrews.

genetics↗

bioRxiv2023

Evolvability of cancer-associated genes under APOBEC3A/B selection

Evolvability is an emergent hallmark of cancer that depends on intra-tumor heterogeneity and, ultimately, genetic variation. Mutations generated by APOBEC3 cytidine deaminases can contribute to genetic variation and the consequences of APOBEC activation differ depending on the stage of cancer, with the most significant impact observed during the early stages. However, how APOBEC activity shapes evolutionary patterns of genes in the host genome and differential impacts on cancer-associated and non-cancer genes remain unclear. Analyzing over 40,000 human protein-coding transcripts, we identified distinct distribution patterns of APOBEC3A/B TC motifs between cancer-related genes and controls, suggesting unique associations with cancer. Studying a bat species with many more APOBEC3 genes, we found diverse motif patterns in orthologs of cancer genes compared to controls, similar to humans and suggesting APOBEC evolution to reduce impacts on the genome rather than the converse. Simulations confirmed that APOBEC-induced heterogeneity enhances cancer evolution, shaping clonal dynamics through bimodal introduction of mutations in certain classes of genes. Our results suggest that a major consequence of the bimodal distribution of APOBEC affects greater cancer heterogeneity. HighlightsO_LIUsing a measure of the extent which genes are affected by APOBEC activity, we found that many genes are maximally robust in the human genome. Interestingly, the distribution in the genome of a bat that has many APOBEC genes was similar. C_LIO_LIIn contrast, when analyzing the subset of cancer-associated genes the distribution is bimodal with many genes appearing to susceptible to APOBEC activity. C_LIO_LIAnalysis of orthologs of human genes and other species showed a wide range in the extent to which APOBEC affects genes having the same function. C_LIO_LIThe bimodal distribution of susceptibility to APOBEC drives greater heterogeneity in simulated clonal evolution of cancer. C_LI

cancer biology↗

bioRxiv2023

Evolutionary potential of the monkeypox genome arising from interactions with human APOBEC3 enzymes

APOBEC3, an enzyme subfamily that plays a role in virus restriction by generating mutations at particular DNA motifs or mutational "hotspots," can drive viral mutagenesis with host-specific preferential hotspot mutations contributing to pathogen variation. While previous analysis of viral genomes from the 2022 Mpox (formerly Monkeypox) disease outbreak has shown a high frequency of C>T mutations at TC motifs, suggesting recent mutations are human APOBEC3-mediated, how emerging monkeypox virus (MPXV) strains will evolve as a consequence of APOBEC3-mediated mutations remains unknown. By measuring hotspot under-representation, depletion at synonymous sites, and a combination of the two, we analyzed APOBEC3-driven evolution in human poxvirus genomes, finding varying hotspot under-representation patterns. While the native poxvirus molluscum contagiosum exhibits a signature consistent with extensive coevolution with human APOBEC3, including depletion of TC hotspots, variola virus shows an intermediate effect consistent with ongoing evolution at the time of eradication. MPXV, likely the result of recent zoonosis, showed many genes with more TC hotspots than expected by chance (over-representation) and fewer GC hotspots than expected (under-representation). These results suggest the MPXV genome: 1) may have evolved in a host with a particular APOBEC GC hotspot preference, 2) has inverted terminal repeat (ITR) regions -which may be exposed to APOBEC3 for longer during viral replication- and longer genes likely to evolve faster, and therefore 3) has a heightened potential for future human APOBEC3-meditated evolution as the virus spreads in the human population. Our predictions of MPXV mutational potential can both help guide future vaccine development and identification of putative drug targets and add urgency to the task of containing human Mpox disease transmission and uncovering the ecology of the virus in its reservoir host.

bioinformatics↗

bioRxiv2022

The macroevolutionary impact of recent and imminent mammal extinctions on Madagascar

Madagascars biota has suffered recent extinctions and many of its unique species are threatened. However, the severity of recent and potential extinctions in a global evolutionary context is unquantified. We compiled a phylogenetic dataset for the complete non-marine mammalian biota of Madagascar and estimated natural rates of extinction, colonization, and speciation. We measured how long it would take to restore Madagascars mammalian biodiversity under these rates, the "evolutionary return time" (ERT). We show the loss of currently threatened Malagasy mammal species would have a much deeper long-term impact than all the extinctions since human arrival to the island. A return from current to pre-human diversity would take 1.6 million years (Myr) for bats, and 2.9 Myr for non-volant mammals. However, if species currently classified as threatened go extinct, the ERT rises to 2.9 Myr for bats and 23 Myr for non-volant mammals. The evolutionary history currently under threat on Madagascar is much greater than on other islands, suggesting an extinction wave with deep evolutionary impact is imminent unless immediate conservation actions are taken.

evolutionary biology↗

bioRxiv2021

Ecological constraints on highly evolvable olfactory receptor genes and morphology

While evolvability of genes and traits may promote specialization during species diversification, how ecology subsequently restricts such variation remains unclear. Chemosensation requires animals to decipher a complex chemical background to locate fitness-related resources, and thus the underlying genomic architecture and morphology must cope with constant exposure to a changing odorant landscape; detecting adaptation amidst extensive chemosensory diversity is an open challenge. Phyllostomid bats, an ecologically diverse clade that evolved plant-visiting from an insectivorous ancestor, suggest the evolution of novel food detection mechanisms is a key innovation: phyllostomids behaviorally rely strongly on olfaction, while echolocation is supplemental. If this is true, exceptional variation in underlying olfactory genes and phenotypes may have preceded dietary diversification. We compared olfactory receptor (OR) genes sequenced from olfactory epithelium transcriptomes and olfactory epithelium surface area of bats with differing diets. Surprisingly, although OR evolution rates were quite variable and generally high, they are largely independent of diet. Olfactory epithelial surface area, however, is relatively larger in plant-visiting bats and there is an inverse relationship between OR evolution rates and surface area. Relatively larger surface areas suggest greater reliance on olfactory detection and stronger constraint on maintaining an already diverse OR repertoire. Instead of the typical case in which specialization and elaboration is coupled with rapid diversification of associated genes, here the relevant genes are already evolving so quickly that increased reliance on smell has led to stabilizing selection, presumably to maintain the ability to consistently discriminate among specific odorants -- a potential ecological constraint on sensory evolution. Significance StatementThe evolutionary relationship between genes and morphology is complex to decipher, and macroevolutionary trends are often measured independently; this is especially challenging to quantify in unstable genomic regions or hypervariable traits. Odorant cues are detected by proteins encoded by the largest and fasted-evolving gene family in the mammalian genome and expressed in epithelia distributed on elaborate bony structures in the nose, posing a challenge to quantification. Yet, the direct interaction of the olfactory system with environmental signals strongly suggest that selection shapes its immense diversity. In neotropical bats, where reliance on plant-visiting evolved from an insectivorous ancestor, we discovered clear dietary differences amongst species, but only after considering morphological and molecular data simultaneously, emphasizing the power of a coupled analysis.

evolutionary biology↗

bioRxiv2019

Targeted sequence capture outperforms RNA-Seq and degenerate-primer PCR cloning for sequencing the largest mammalian multi-gene family

Multigene families evolve from single-copy ancestral genes via duplication, and typically encode proteins critical to key biological processes. Molecular analyses of these gene families require high-confidence sequences, but the high sequence similarity of the members can create challenges for both sequencing and downstream analyses. Focusing on the common vampire bat, Desmodus rotundus, we evaluated how different sequencing approaches performed in recovering the largest mammalian protein-coding multigene family: olfactory receptors (OR). Using the common vampire bat genome as a reference, we determined the proportion of putatively protein-coding receptors recovered by: 1) amplicons from degenerate primers sequenced via Sanger technology, 2) RNA-Seq of the main olfactory epithelium, and 3) those genes \"captured\" with probes designed from transcriptomes of closely-related species. Our initial re-annotation of the high-quality vampire bat genome resulted in >400 intact OR genes, more than double the number based on original estimates. Sanger-sequenced amplicons performed the poorest among the three approaches, detecting <33% of receptors in the genome. In contrast, the transcriptome reliably recovered >50% of the annotated genomic ORs, and targeted sequence capture recovered nearly 75% of annotated genes. Each sequencing approach assembled high-quality sequences, even if it did not recover all putative receptors in the genome. Therefore, variation among assemblies was caused by low coverage of some receptors, rather than high rates of assembly error. Given this variability, we caution against using the counts of number of intact receptors per species to model the birth-death process of multigene families. Instead, our results support the use of orthologous sequences to explore and model the evolutionary processes shaping these genes.

genomics↗

bioRxiv2018

Evidence for multifactorial processes underlying phenotypic variation in bat visual opsins

Studies of opsin genes offer insights into the evolutionary history and molecular basis of vertebrate color vision, but most assume intact open reading frames equate to functional phenotypes. Despite known variation in opsin repertoires and associated visual phenotypes, the genetic basis of such patterns has not been examined at each step of the central dogma. By comparing sequences, gene expression, and protein localization across a hyperdiverse group of mammals, noctilionoid bats, we find evidence that independent losses of S-opsin arose through disruptions at different stages of protein synthesis, while maintenance relates to frugivory. Discordance between DNA, RNA, and protein reveals that the loss of short-wave sensitivity in some lineages resulted from transcriptional and post-transcriptional changes in addition to degradation of open reading frames. These mismatches imply that visual phenotypes cannot reliably be predicted from genotypes alone, and connect ecology to multiple mechanisms behind the loss of color in vertebrates.

genomics↗

bioRxiv2018

Expressed vomeronasal type-1 receptors (V1rs) in bats uncover conserved mechanisms of social chemical signaling

In mammals, social and reproductive behaviors are mediated by chemical cues encoded by hyperdiverse families of receptors expressed in the vomeronasal organ. Between species, the number of intact receptors can vary by orders of magnitude. However, the evolutionary processes behind variation in receptor number, and also its link to fitness-related behaviors are not well understood. From vomeronasal transcriptomes, we discovered the first evidence of intact vomeronasal type-1 receptor (V1r) genes in bats, and we tested whether putatively functional bat receptors were orthologous to those of related taxa, or whether bats have evolved novel receptors. We found that V1rs in bats and show high levels of orthology to those of their relatives, as opposed to lineage-specific duplications, and receptors are under purifying selection. Despite widespread vomeronasal organ loss in bats, V1r copies have been retained for >65 million years. The highly conserved nature of bat V1rs challenges our current understanding of mammalian V1r function and suggest roles other than conspecific recognition or mating initiation in social behavior.

evolutionary biology↗