A study published today in the leading academic journal Nature sequenced the genomes of six different species of live bats, including: Rhinolophus ferrumequinum, Egyptian fruit bat (Rousettus aegyptiacus), Phyllostomus discolor, rat ear bat (Myotis myotis), Pipistrellus kuhlii and Mastiff Molossus molossus.
This study reveals the genes behind certain "superpowers" of bats, such as unique flight capabilities, echolocation navigation capabilities, anti-aging ultra-long lifespans, and unique immunity/cancer-fighting viral abilities.
While genomes from other bats have been published before, the genomes released by the Bat1K Global Genome Consortium (http://bat1k.com) and the Vertebrate Genome Project (https://vertebrategenomesproject.org) are 10 times more complete than any bat genome published to date. This is the first high-quality reference genome for these 6 species of bats. A high-quality genome is critical to understanding the molecular basis and evolution of the above traits.
Figure 1: Assembly of six bat genomes.
Integrating the latest sequencing technology and assembly algorithms, the high-quality genomic data obtained by the research team this time is two orders of magnitude higher in continuity than the previously published bat genome sequences, and has reached nearly 100% genetic integrity. For about 20,000 genes encoding proteins in each bat, the researchers made highly complete gene annotations.
Through genome-wide screening, the researchers found that some immune-related genes were evolutionarily positively selected, suggesting that the common ancestor of bats began to evolve immunomodulatory mechanisms that were different from those of other mammals.
One aspect of the paper's findings suggests that gene expansion and loss in the APOBEC3 gene family led to evolution, and that the APOBEC3 gene plays an important role in viral immunity in other mammals.
The paper explains the details of this evolutionary process, laying the groundwork for studying how these genetic changes, found in bats but not found in other mammals, could help prevent other mammals, including humans, from contracting viral diseases.
In a second genome-wide screening, they systematically screened for gene loss using previously developed methods. This reveals that 10 genes are inactivated in 6 species of bats, but are also present in most non-bats in Laurasiatheria. Two of the lost genes have immunostimulatory functions (Figure 3a). For example, several genes that regulate the NF-κB signaling pathway and encode pro-inflammatory factors lose their activity.
Figure 3: Genome-wide screening shows genetic changes that may be involved in abnormal immunity in bats.
For the third time, they investigated changes in gene family size and found that 35 gene families showed significant expansion or contraction in bat ancestors. Among them, the amplification of the presumed APOBEC3 site led to the amplification of the APOBEC gene family (Figure 3c), and the APOBEC3 site is known to show a complex history of repetition and loss in the flying fox (winged fox) and other mammals. Detailed experimental analysis showed a small amplification of APOBEC3 in the ancestral lineage of bats, followed by multiple, lineage-specific amplifications involving up to 14 repetitive events, including the production of a second APOBEC3 locus in myositis. Amplification of the APOBEC3 gene in multiple bat lines may have contributed to the virus's tolerance in these lines.
Integrative viruses in bat genomes
There is growing evidence that bats tolerate and survive viral infections more than most mammals, thanks to the adaptability of their immune responses.
This is supported by the selection and deletion of immune-related genes identified in the study and the amplification of viral restrictions on the APOBEC3 gene. Because viral infections can leave traces in the host genome in the form of endogenous viral elements (EVEs), they screened the genomes of bats to determine whether they contained more numbers and diversity of EVEs than other mammals. First, they focused on nonretroviruses, which are typically found in smaller amounts in animal genomes than endogenous retroviruses (ERVs). In bat individuals and other mammalian populations, the researchers identified three main nonretroviral families — parvoviridae, adenoviridae, and bornaviridae (extended figure 8a). They also detected a partial filovirus in the vesicle linden family (Pipistrellus and Myotis), which is consistent with previous reports that vesicle linden bats have been exposed to filamentovirus infection in the past and survived.
"We are increasingly finding that the duplication and loss of genes is an important process in the evolution of new traits and functions throughout the tree of life. But if the genome is incomplete, it's hard to determine when genes replicate, and it's even harder to figure out if genes are missing. In extremely high-quality cases, the new bat genomes undoubtedly alter important gene families that cannot be found in low-mass genomes.
To generate the bat's genome, the team used the latest technology from Dresden,Germany's shared technology resource, dresden-Conceptual Genome Center, to sequence the bat's DNA and developed new ways to assemble the fragments in the correct order and then identify genes that currently exist.
While previous efforts have identified genes that may affect bats' unique biology, incomplete genomes complicate the discovery of how gene duplication affects this unique biology.
The team compared the bats' genomes with 42 other mammal species to understand where the bats were in the mammalian tree of life. Using new phylogenetic methods and comprehensive molecular datasets, the team found evidence that bats are the closest to the genomes of Fereuungulata, which consist of carnivores (including species such as dogs, cats, and seals), lepidoptera (pangolins), cetaceans (whales), and odd-ungulates (ungulate mammals).
To discover genomic changes that lead to changes in bats' unique adaptability, the team systematically searched for genetic differences between bats and other mammals, identifying regions of bat genomes that evolved differently, as well as genetic gains and losses that could lead to unique traits in bats.
"Thanks to a series of sophisticated statistical analyses, we began to discover the genes behind bats' 'superpowers,' including their apparent tolerance and ability to defeat RNA viruses," said Liliana M. Davalos, an evolutionary biologist and co-author at Stony Brook University.
The researchers found that the delicate genome revealed "viral fossils," demonstrating evidence of survival prior to viral infection and showing that the genomes of bats contained a higher diversity of viral residues than other species, providing a genomic record of interactions with viral infections in ancient times. These genomes also show signs of many other genetic elements besides ancient viral insertions, including "jumping genes" or transposing factors.
"These reference genomes will be an important tool for studying how bats tolerate coronavirus infections, or may enhance human viability in the face of diseases like COVID-19." The study authors noted in the paper. In addition, understanding the amazing immunity and life extension mechanisms of bats at the molecular level can also help to develop new targets for delaying human aging and treating diseases.
Compilation/Prospective Economist APP Information Group
Reference: https://scitechdaily.com/genetics-of-bat-superpowers-revealed-how-they-fly-survive-deadly-viruses-resist-aging-and-cancer/
https://www.nature.com/articles/s41586-020-2486-3
https://www.mirror.co.uk/science/scientists-discover-how-bats-survive-22397642
https://www.heraldscotland.com/news/18601393.bat-scientists-crack-code-behind-so-called-super-powers/