Long-read sequencing reveals rapid evolution of immunity- and cancer-related genes in bats

Abstract

Bats are exceptional among mammals for harbouring diverse pathogens and for their robust immune systems. In addition, bats are unusually long-lived and show low rates of cancer. Contiguous and complete reference genomes are needed to determine the genetic basis of these adaptations and establish bats as models for research into mammalian health. Here we sequenced and analysed the genomes of the Jamaican fruit bat (Artibeus jamaicensis) and the Mesoamerican mustached bat (Pteronotus mesoamericanus). We sequenced these two species using a mix of Illumina and Oxford Nanopore Technologies (ONT), assembling draft genomes with some of the highest contig N50s (28-29Mb) of bat genomes to date. Work is in progress to increase the base-level accuracies of these genomes. We conducted gene annotation and identified a set of 10,928 orthologs from bats and mammalian outgroups including humans, rodents, horses, pigs, and dogs. To detect positively selected genes as well as lineage-specific gene gains and losses, we carried out comprehensive branch-site likelihood ratio tests and gene family size analyses. Our analysis found signatures of rapid evolution in the innate immune response genes of bats, and evidence of past infections with diverse viral clades in Artibeus jamaicensis and Pteronotus mesoamericanus. We additionally found evidence of positive selection of tumor suppressors, which may play a role in the low cancer rates, in the most recent common ancestor of bats. These new genomic resources enable insights into the extraordinary adaptations of bats, with implications for mammalian evolutionary studies and public health.

Gene losses in the common vampire bat illuminate molecular adaptations to blood feeding

“…This indicates a substantially higher gene completeness in our assemblies, similar to the most contiguous bat assemblies generated to date ( Fig. 1C ) ( 25 , 26 ).…”

Reference-quality bat genomes illuminate adaptations to viral tolerance and disease resistance

“…Consistent with a previous HiFi-based bat assembly 40 , we estimate a very high base accuracy (QV=61.8-69.7, indicating <1 error per megabase) for our nine HiFi-based assemblies. These base accuracy values are two orders of magnitude higher compared with previous PacBio CLR or Nanopore-based assemblies 28,29 .…”

“…For Chiroptera, we included the 10 new and ten previously published bat assemblies. 18 of these 20 bats were assembled from long sequencing reads 28,29,40 while the remaining two genomes were assembled from Illumina short-read data 149,150 (Supplementary Table 3). For five mammalian orders (Primates, Rodentia, Cetartiodactyla, Carnivora, Chiroptera), we selected exactly 20 species.…”

“…Genomic analyses revealed insights into immune system changes that may contribute to enhanced resistance to viral disease in bats, such as selection of viral entry factors and innate immune response genes 18,[25][26][27][28] , diversified activating and inhibiting natural killer cell receptors 18 , selection and losses of pro-inflammatory genes that regulate canonical NF-κB signaling 29 , expansions and contractions of type 1 interferon genes 18,28,30 , and the absence of PHYIN genes that activate inflammasomes 25,31 . Further studies have revealed a general dampening of the inflammasome system to multiple immune stimuli 32,33 .…”

Molecular, ecological, and behavioral drivers of the bat-virus relationship

“…However, this unique distribution and expression of IRF7 was not detected in other bat species, such as Rousettus aegyptiacus (Pavlovich et al, 2018), although similar results have been observed in some species of fish, such as the crucian carp (Carassius auratus L.) (Zhang et al, 2003). Thus, different bat species may have evolved alternative antiviral strategies, including a potential shift toward an IFNu driven response relative to IFNa in at least 10 bat species (Scheben et al, 2021). Additionally, positive selection of a serine residue at the 185 th position in IRF3 has been shown to have enhanced antiviral properties in E. fuscus and P. alecto bat cells (Banerjee et al, 2020d).…”