Bat Biology, Genomes, and the Bat1K Project: To Generate Chromosome-Level Genomes for All Living Bat Species

Abstract

Bats are unique among mammals, possessing some of the rarest mammalian adaptations, including true self-powered flight, laryngeal echolocation, exceptional longevity, unique immunity, contracted genomes, and vocal learning. They provide key ecosystem services, pollinating tropical plants, dispersing seeds, and controlling insect pest populations, thus driving healthy ecosystems. They account for more than 20% of all living mammalian diversity, and their crown-group evolutionary history dates back to the Eocene. Despite their great numbers and diversity, many species are threatened and endangered. Here we announce Bat1K, an initiative to sequence the genomes of all living bat species (n ∼ 1,300) to chromosome-level assembly. The Bat1K genome consortium unites bat biologists (>148 members as of writing), computational scientists, conservation organizations, genome technologists, and any interested individuals committed to a better understanding of the genetic and evolutionary mechanisms that underlie the unique adaptations of bats. Our aim is to catalog the unique genetic diversity present in all living bats to better understand the molecular basis of their unique adaptations; uncover their evolutionary history; link genotype with phenotype; and ultimately better understand, promote, and conserve bats. Here we review the unique adaptations of bats and highlight how chromosome-level genome assemblies can uncover the molecular basis of these traits. We present a novel sequencing and assembly strategy and review the striking societal and scientific benefits that will result from the Bat1K initiative.

Viruses in bats and potential spillover to animals and humans

“…Bats are not only rich in species diversity, but also have great variation in their geographical locations, dietary preferences, physiological range of body temperatures, social behaviour and navigation and vision systems [11]. It is therefore important to recognise that such immense diversity makes it difficult to generalize-specific associations relating to bats and viruses to all members of the chiropteran order.…”

Reprogrammed Pteropus Bat Stem Cells Present Distinct Immune Signature and are Highly Permissive for Henipaviruses

“…A large number of novel bat virus sequences 24 was identified in these two bat suborders, which diverged over 50 million years ago, suggesting a 25 long co-evolutionary history of bats and their viruses that have shaped unique host-pathogen 26 relationships 19 . In addition, bats harbor a markedly higher proportion of zoonotic viruses than other 27 mammalian orders 20,21 . Although bat serology and viral genome sequencing permit detection of a 28 number of bat viruses, isolating them has been far more challenging.…”

“…These 24 reprogrammed cells are much more highly susceptible to virus infection than the parental primary bat 25 cells, making them a new cell type that can be used to isolate novel bat viruses and study host- 26 pathogen interactions. Interestingly, in contrast to stem cells from other mammalian species, bat RSCs 27 are capable of both responding to and producing IFN-I, and present a unique interferon-stimulated 28 gene (ISG) transcriptomic signature, suggesting some fundamental differences between bats and 29 other mammals. This new cell model is an important experimental tool that will improve 30 understanding of the unique properties of bat/virus interactions and will help to decipher novel aspects 31 of bat biology.…”

“…1c, d). 25 Next, we screened additional transcription factors for their ability to induce somatic 26 reprogramming of bat PCs through delivery of doxycycline-inducible transposons and identified a 27 novel gene combination (ESRRB, CDX2, and c-MYC) as highly efficient at inducing marked and 28 stable morphological changes in transduced bat PCs. When cells were cultured in serum-free EPI 29 medium, foci showing typical stem cell morphology appeared at around 25 days after addition of 30 doxycycline ( Fig.…”

“…24 25 Bat RSCs are highly permissive for Henipavirus infection. As Pteropus bats are the recognized 26 natural reservoir of Henipaviruses, we tested the susceptibility of bat PCs and bat RSCs to infection 27 by two human NiV isolates (NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B)), one Pteropus 28 bat NiV isolate (NiV Cambodia (NiV-C)), and one equine HeV isolate. Viral entry into cells was 29 quantified using recombinant vesicular stomatitis virus (VSV), which lacks envelope glycoprotein G, 30 replaced by red fluorescent protein (rVSVΔG-RFP), pseudotyped with surface glycoproteins G and 31 F from each Henipavirus isolate.…”