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Despite a small genome size, bats have comparable diversity of retroviral and non-retroviral endogenous sequences to other mammals. These include Class I and Class II retroviral sequences, foamy viruses, and deltaretroviruses, as well as filovirus, bornavirus, and parvovirus endogenous viral elements. Some of these endogenous viruses are sufficiently preserved in bat genomes to be expressed, with potential effects for host biology. It is clear that the bat immune system differs when compared with other mammals, yet the role that virus-derived endogenous elements may have played in the evolution of bat immunity is poorly understood. In this review, we discuss some of the bat-specific immune mechanisms that may have resulted in a virus-tolerant phenotype and link these to the long-standing virus-host coevolution that may have allowed a large diversity of endogenous retroviruses and other endogenous viral elements to colonize bat genomes. We also consider the possible effects of endogenization in the evolution of the bat immune system.

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 protocols 1 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 disease 1 .

Bats are the primary reservoirs and carriers of a wide range of viruses of unknown infectivity and pathogenic potential. Some of those if transmitted to other species can cause enormous economic losses in agriculture, and mortality in humans. Bats can be persistently infected with viruses while not showing any symptoms of disease, despite having high virus titre levels in their tissues and shedding virions for months or years after primary infection. It has been suggested that the lack of symptoms of viral infections and low mortality rate in bats might be due to immune adaptations that result from their long-term co-evolution with viruses. In this study, we screened all publicly available bat genomes from six bat families within which we have identified several envelope sequences of retroviral origin (gammaretroviruses). We analysed the identified sequences with Bayesian methods and maximum-likelihood inference to generate a phylogenetic tree with additional reference sequences of known endogenous and exogenous viral envelope genes. We also identified groups of orthologous viral envelopes and analysed them to determine if any of them might be an EVE (endogenous virus element) with an EDI (EVE- derived immunity) function or a candidate for a bat syncytin gene, which is an endogenized viral envelope, mostly known from its function in placentation in animals. Our study shows that bat genomes contain a substantial number of large, intact envelopes with open reading frames, which were found clustering closely on a phylogenetic tree reconstruction with syncytin sequences of other species. That might indicate that such sequences are good candidates for further bat-syncytin/EDI search., (Copyright © 2019. Published by Elsevier B.V.)