Six new reference-quality bat genomes illuminate the molecular basis and evolution of bat adaptations

Background: Bats are one of the most fascinating groups of animals. With ~1400 species representing no less than 20% of mammals, they are considered to be an evolutionary success. Their particularity also lies in their range of specialized adaptations such as specialized sensory organs (including echolocation), unparalleled immune systems and the ability to tolerate viruses known to be lethal to other mammals, extreme morphological adaptations, the largest diversity of mammalian diets and an extreme longevity. But their origin remains somewhat unclear: while the incredible diversification of bats has been hypothesized to be linked to the acquisition of powered flight that allowed the occupation of a wide variety of ecological niches, their position within the mammalian tree is still debated. To understand what could have led to this extraordinary diversification and to set up new models for aging, sensory evolution and enhanced disease tolerance, studying genomes can bring some first clues by identifying genetic signatures responsible for these adaptations, as well as help resolve the position of bats in the tree of life. The preprint presents the genome of 6 bat species representative of bat diversity.

Methods: The key methods of this paper are to produce high quality, near-complete genomes that represent the state of the art of genome sequencing and assembly. To do so, the authors combined four different sequencing techniques of third generation sequencing (10x Genomics Illumina, PacBio long read, Bionano optical and HI-C Illumina) to allow a very reliable assembly with low errors. This is achieved by producing long reads (i.e. long fragments sequenced), optical mapping (that allows the physical placing of sequences onto the chromosomes), and chromosome conformation capture (that maps the 3D organization of the chromosome and the sequence in the nucleus). The authors integrated data from previously published bat and other mammalian genomes as well as de novo alignments and transcriptomes to produce a very accurate genome annotation.

Key findings:

• Placing Chiroptera within Laurasiatheria: The position of bats in the mammalian tree has been a long-standing question. Bats are nested in Laurasiatheria (the group that contains carnivorans and cattle) but their position within laurasiatherians has remained debated. As phylogenetic trees are based on molecular and genomic analysis, having 6 new complete genomes sequenced should incredibly enhance the resolution of problematic branches by comparison with other genomes. Taking advantage of the completeness of their genome annotations, the authors used almost 13000 orthologs (genes that are also present others species) of protein coding genes, but also non-coding elements as a base to reconstruct the phylogenetic tree. While these analyses did not definitely resolve the position of Chiroptera, they show that the majority of the genome supports Chiroptera as the sister clade of a group known as Ferungulata, comprising even-toed ungulate (goats, giraffes, cattle and cetaceans), carnivores, odd-toed ungulate and pangolins.

 

• Gene selection, losses and gains: As alleles under positive selection are the ones responsible for an advantageous phenotype, identifying them, in particular for the ancestral bat, can bring crucial information about the evolution of this group and its incredible adaptations. The authors discover 9 genes under strong positive selection among the nearly 13k genes retained for this test. Interestingly, three of these genes are hearing related, two of them being mutated in non-echolocating bats, while three are related to immunity and may be linked to the ability of bats to resist many mammalian diseases. Further analysis found 10 other genes under positive selection that are involved in pathogen response, cell proliferation, and anti-aging. As gene loss is more and more considered an important mechanism for the evolution of species, the authors also looked for significant gene losses among the different species of bats. This analysis sorted out 10 genes, two of them being linked to immunity, further supporting bats as a promising model for immunity. Strikingly, when the authors investigated gene family expansions and contractions in the ancestors of bats, they found, in particular, an expansion of the APOBEC family, which includes DNA/RNA editing enzymes that can contribute to viral tolerance.

 

• Integrated viruses in bat genomes: As bats are suspected to be a major reservoir for many viruses such as rabies, Ebola or MERs, the authors screen for the presence of endogenous viral elements (considered as traces of ancient viral infections) and ERVs (endogenous retroviruses) that could also explain the bat tolerance to these viruses. They identified three non-retroviral families in some family of bats showing that some species underwent and can resist to certain viral infections. Interestingly, they also discovered the presence of alpharetroviral-like elements, a viral group that was thought to be found only in avian genomes. Along with further analysis, these results revealed that bats possess a high diversity of ERV in their genomes suggesting complex interaction between bats and viruses that normally don’t endogenize.

 

• Change in non-coding RNAs: as the evolution of non-coding RNA can drive adaptation, the authors studied the evolution of these elements in the bat genomes. They found that the majority of bat lncRNA are shared with other mammals. The investigation of miRNA families, which are important gene expression regulators, reveal some contraction of some families, including one implicated in cancer, and a new burst of miRNA in bats. One single-copy miRNA was found to contain a mutation functionally unique to bats.

 

Conclusion – what I liked about this preprint: By providing high quality genomes, the authors were able to point out some important characteristics of bat genomes that constitute a first base for future investigations as well as revealing interesting characteristics of bats. As an evolutionary developmental biologist working on bats, I was particularly excited by 1) finally having the ability to explore the evolution of bat genomes and looking for signatures of adaptation, 2) the release of state-of-the-art high quality genomes that constitute the foundation for many experiments, including almost all kinds of gene expression analyses that are crucial to ask questions about the origin of bat diversity, the evolution of organ shape or type or the investigation of rules that govern species evolution.

Questions:

How does the observed phylogeny inform the fossil record? In the context of the bat1K, will the new data be sufficient to resolve the position of bats? Which analysis or data are the most promising to resolve the position of bats?

How can you explain this surprising trend of widespread miRNA family contraction in bats? What could be the possible consequences on the gene expression regulation network?

Given the high variability of ecological niches occupy by bats, how do you expect these genomic trends to be conserved in other species? What are you expecting to find for highly dietary or morphologically specialized species?

Tags: adaptation, bat, evolution, evolutionary biology, genome

doi: https://doi.org/10.1242/prelights.16759

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