Genomics of exceptions to scaling of longevity to body size
Professor of Conservation Biology
I’m interested in how biology and the environment shape biodiversity in time and space.
- Immunological adaptations in bats to moderate the effect of coronavirus infection
- Regrowing the brain; evolution and mechanisms of seasonal reversible size changes in a mammal
- Discovering genomic and developmental mechanisms that underlie sensory innovations critical to adaptive diversification
- Global Union of Bat Diversity Networks (GBatNet)
- Bat goblet cells as immuno-hotspots for infection of coronavirus
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.
A de novo assessment of TE content in 248 mammals finds informative trends in mammalian genome evolution.
Austin B. Osmanski, Nicole S. Paulat, Jenny Korstian, Jenna R. Grimshaw, Michaela Halsey, Kevin A.M. Sullivan, Diana D. Moreno-Santillán, Claudia Crookshanks, Jacquelyn Roberts, Carlos Garcia, Matthew G. Johnson, Llewellyn D. Densmore, Richard D. Stevens, Zoonomia Consortium, Jeb Rosen, Jessica M. Storer, Robert Hubley, Arian F.A. Smit, Liliana M. Dávalos, Kerstin Lindblad-Toh, Elinor K. Karlsson, David A. Ray
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.
Nicole S. Paulat, Jessica M. Storer, Diana D. Moreno-Santillán, Austin B. Osmanski, Kevin A.M. Sullivan, Jenna R Grimshaw, Jennifer Korstian, Michaela Halsey, Carlos Garcia, Claudia Crookshanks, Jaquelyn Roberts, Arian F.A. Smit, Robert Hubley, Jeb Rosen, Emma C. Teeling, Sonja C. Vernes, Eugene Myers, Martin Pippel, Thomas Brown, Michael Hiller, Zoonomia Consortium, Danny Rojas, Liliana M. Dávalos, Kerstin Lindblad-Toh, Elinor K. Karlsson, David A. Ray
Bats carry viruses that can cause severe disease in other mammals. Asymptomatic infections in bats suggest limited tissue-damaging inflammation and immunopathology. To investigate the genomic basis of disease resistance, the Bat1K project generated reference-quality genomes of ten bat species. A systematic analysis showed that signatures of selection in immune genes are more prevalent in bats compared with other mammals. We found an excess of immune gene adaptations in the ancestral Chiroptera and many descending bat lineages, highlighting viral entry and detection factors, and regulators of antiviral and inflammatory responses. ISG15, an antiviral gene contributing to hyperinflammation during COVID-19, exhibits a deletion of a cysteine, required for homodimer formation, in rhinolophid and hipposiderid bats. Cellular infection experiments showed enhanced intracellular protein conjugation of bat ISG15 and lack of secretion into extracellular space, where human ISG15 stimulates inflammation. Our work highlights molecular mechanisms contributing to viral tolerance and disease resistance in bats.
Ariadna E. Morales, Yue Dong, Thomas Brown, Kaushal Baid, Dimitrios - Georgios Kontopoulos, Victoria Gonzalez, Zixia Huang, Alexis-Walid Ahmed, Leon Hilgers, Sylke Winkler, Graham M. Hughes, Xiaomeng Li, Bogdan M. Kirilenko, Paolo Devanna, Tanya M. Lama, Yomiran Nissan, Martin Pippel, Liliana M. Dávalos, Sonja C. Vernes, Sebastien J. Puechmaille, Stephen J. Rossiter, Yossi Yovel, Joseph B. Prescott, Andreas Kurth, David A. Ray, Burton K. Lim, Eugene Myers, Emma C. Teeling, Arinjay Banerjee, Aaron T. Irving, Michael Hiller
Ecological constraints on highly evolvable olfactory receptor genes and morphology in neotropical bats
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. In phyllostomid bats, an ecologically diverse clade that evolved plant-visiting from an insectivorous ancestor, the evolution of novel food detection mechanisms is suggested to be a key innovation, as plant-visiting species rely strongly on olfaction, supplementarily using echolocation. 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 are 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.
Laurel R. Yohe, Matteo Fabbri, Daniela Lee, Kalina T. J. Davies, Thomas P. Yohe, Miluska K.R. Sanchez, Edgardo M. Rengifo, Ronald P. Hall, Gregory L. Mutumi, Brandon P. Hedrick, Alexa Sadier, Nancy B. Simmons, Karen E. Sears, Elizabeth R. Dumont, Stephen J. Rossiter, Bhart-Anjan Bullar, Liliana M. Dávalos
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 repertoire diversity 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 specialized OR repertoires with narrower diversity has never been tested. Using targeted sequence capture, we sequenced the OR repertoires of three sympatric species of short-tailed fruit 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 explored the diversity and redundancy of the receptor gene repertoire. At the species level, the most dedicated Piper specialist, Carollia castanea, had lower OR diversity compared to the two generalists (C. sowelli, C. perspicillata), but we discovered a few unique sets of ORs within C. castanea with high redundancy of similar gene duplicates. These unique receptors potentially enable C. castanea to detect Piper fruit odorants better than its two congeners. Carollia perspicillata, the species with the most generalist diet, had a higher diversity of intact receptors, suggesting the ability to detect a wider range of odorant molecules. 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 and changes in OR diversity may play a role in dietary adaptations and underlies patterns of ecological interactions between bats and plants.
Comprising more than 1,400 species, bats possess adaptations unique among mammals including powered flight, unexpected longevity, and …
Diana D. Moreno-Santillán, Tanya Lama, Yocelyn Gutiérrez Guerrero, Alexis Brown, Paul Donat, Huabin Zhao, Stephen Rossiter, Laurel R. Yohe, Joshua Potter, Emma C. Teeling, Sonja Vernes, Kalina T.J. Davies, Eugene Myers, Graham M. Hughes, Zixia Huang, Federico G. Hoffmann, Angelique P. Corthals, David Ray, Liliana M. Dávalos
Where the wild things were: intrinsic and extrinsic extinction predictors in the world's most depleted mammal fauna
Preventing extinctions requires understanding macroecological patterns of vulnerability or persistence. However, correlates of risk can …
Bats possess extraordinary adaptations, including flight, echolocation, extreme longevity and unique immunity. High-quality genomes are crucial for understanding the molecular basis and evolution of these traits. Here we incorporated long-read sequencing and state-of-the-art scaffolding protocols1 to generate, to our knowledge, the first reference-quality genomes of six bat species (Rhinolophus ferrumequinum, Rousettus aegyptiacus, Phyllostomus discolor, Myotis myotis, Pipistrellus kuhlii and Molossus molossus). We integrated gene projections from our ‘Tool to infer Orthologs from Genome Alignments’ (TOGA) software with de novo and homology gene predictions as well as short- and long-read transcriptomics to generate highly complete gene annotations. To resolve the phylogenetic position of bats within Laurasiatheria, we applied several phylogenetic methods to comprehensive sets of orthologous protein-coding and noncoding regions of the genome, and identified a basal origin for bats within Scrotifera. Our genome-wide screens revealed positive selection on hearing-related genes in the ancestral branch of bats, which is indicative of laryngeal echolocation being an ancestral trait in this clade. We found selection and loss of immunity-related genes (including pro-inflammatory NF-κB regulators) and expansions of anti-viral APOBEC3 genes, which highlights molecular mechanisms that may contribute to the exceptional immunity of bats. Genomic integrations of diverse viruses provide a genomic record of historical tolerance to viral infection in bats. Finally, we found and experimentally validated bat-specific variation in microRNAs, which may regulate bat-specific gene-expression programs. Our reference-quality bat genomes provide the resources required to uncover and validate the genomic basis of adaptations of bats, and stimulate new avenues of research that are directly relevant to human health and disease1.
David Jebb, Zixia Huang, Martin Pippel, Graham M. Hughes, Ksenia Lavrichenko, Paolo Devanna, Sylke Winkler, Lars S. Jermiin, Emilia C. Skirmuntt, Aris Katzourakis, Lucy Burkitt-Gray, David A. Ray, Kevin A. M. Sullivan, Juliana G. Roscito, Bogdan M. Kirilenko, Liliana M. Dávalos, Angelique P. Corthals, Megan L. Power, Gareth Jones, Roger D. Ransome, Dina Dechmann, Andrea G. Locatelli, Sebastien J. Puechmaille, Olivier Fedrigo, Erich D. Jarvis, Mark S. Springer, Michael Hiller, Sonja C. Vernes, Eugene W. Myers, Emma C. Teeling
Within‐clade allometric relationships represent standard laws of scaling between energy and size, and their outliers provide new …
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.
As high-throughput sequencing technologies advance, standardized methods for high quality tissue acquisition and preservation allow for …