Two Texas Tech University researchers were involved in analyzing the first six reference-quality bat genomes.
For the first time, the raw genetic material that codes for bats' unique adaptations and superpowers – such as the ability to fly, use sound to move effortlessly in complete darkness, survive and tolerate deadly diseases and resist aging and cancer – has been fully revealed and published in Nature.
Bat1K, a global consortium of scientists dedicated to sequencing the genomes of every one of the 1,421 living bat species, has generated and analyzed six highly accurate bat genomes that are 10 times more complete than any bat genome published to date, in order to begin to uncover bats' unique traits.
"Given these exquisite bat genomes, we can now better understand how bats tolerate viruses, slow down aging and have evolved flight and echolocation," said Emma Teeling of University College Dublin, co-founding director of Bat1K and senior author on the paper. "These genomes are the tools needed to identify the genetic solutions evolved in bats that ultimately could be harnessed to alleviate human aging and disease."
As part of the consortium, two researchers in Texas Tech University's Department of Biological Sciences, associate professor David A. Ray and doctoral candidate Kevin Sullivan, played a pivotal role in the genome analysis.
"Our lab was tasked with analyzing the portions of each genome that are made up of transposable elements, parts of the genome that can move around and potentially disrupt or alter function," Ray said. "We found that, unlike most other groups of mammals, bats have an exceptionally diverse transposable element repertoire. This suggests their genomes may have the ability to change and adapt to novel environments above and beyond what a 'typical' mammal can do. This may explain what appears to be their increased ability to tolerate viruses and live longer, healthier lives than would be expected given their size."
Ray explained that a perfectly assembled genome would have the same number of pieces as there are chromosomes for that species. For example, humans have 23 pairs of chromosomes so a very good assembly would consist of 23 pieces of assembled DNA. In contrast, bad genome assemblies have thousands of pieces, meaning the assembly is very fragmented. Because these bat genomes have very few pieces, the researchers refer to them as "exquisite" genomes.
To generate these exquisite bat genomes, the Bat1K team used the newest technologies of the DRESDEN-concept Genome Center, a shared technology resource in Dresden, Germany, to sequence the bat's DNA, and generated new methods to assemble these pieces into the correct order and to identify the genes present.
"Using the latest DNA sequencing technologies and new computing methods for such data, we have 96-99% of each bat genome in chromosome-level reconstructions – an unprecedented quality akin to, for example, the current human genome reference, which is the result of over a decade of intensive 'finishing' efforts," said senior author Eugene Myers, director of Max Planck Institute of Molecular Cell Biology and Genetics, and the Center for Systems Biology in Dresden. "As such, these bat genomes provide a superb foundation for experimentation and evolutionary studies of bats' fascinating abilities and physiological properties."
The team compared these bat genomes against 42 other mammals to address the unresolved question of where bats are located within the mammalian tree of life. Using novel phylogenetic methods and comprehensive molecular data sets, the team found the strongest support for bats being most closely related to a group called Ferreungulata that consists of carnivores (which includes dogs, cats and seals, among other species), pangolins, whales and ungulates (hooved mammals).
To uncover genomic changes that contribute to the unique adaptations found in bats, the team systematically searched for gene differences between bats and other mammals, identifying regions of the genome that have evolved differently in bats and the loss and gain of genes that may drive bats' unique traits.
"Our genome scans revealed changes in hearing genes that may contribute to echolocation, which bats use to hunt and navigate in complete darkness," said senior author Michael Hiller, research group leader in the Max Planck Institute of Molecular Cell Biology and Genetics, the Max Planck Institute for the Physics of Complex Systems and the Center for Systems Biology.
"Furthermore, we found expansions of anti-viral genes, unique selection on immune genes, and loss of genes involved in inflammation in bats. These changes may contribute to bats' exceptional immunity and points to their tolerance of coronaviruses."
The team also found evidence that bats' ability to tolerate viruses is reflected in their genomes. The exquisite genomes revealed "fossilized viruses," evidence of surviving past viral infections, and showed that bat genomes contained a higher diversity than other species providing a genomic record of historical tolerance to viral infection.
Given the quality of the bat genomes, the team uniquely identified and experimentally validated several non-coding regulatory regions that may govern bats' key evolutionary innovations.
"Having such complete genomes allowed us to identify regulatory regions that control gene expression that are unique to bats," said senior author Sonja Vernes of the Max Planck Institute for Psycholinguistics and co-founding director of Bat 1K. "Importantly, we were able to validate unique bat microRNAs in the lab to show their consequences for gene regulation. In the future we can use these genomes to understand how regulatory regions and epigenomics contributed to the extraordinary adaptations we see in bats."
This is just a beginning. The remaining approximately 1,400 living bat species exhibit an incredible diversity in ecology, longevity, sensory perception and immunology, and numerous questions remain regarding the genomic basis of these spectacular features. Bat1K will answer these questions as more and more exquisite bat genomes are sequenced, further uncovering the genetic basis of bats' rare and wonderful superpowers.
This study was funded in part by the Max Planck Society, the European Research Council, the Irish Research Council and the Human Frontier Science Program.
In addition to Texas Tech, the institutions contributing to the research are: University College Dublin; Max Planck Institute of Molecular Cell Biology and Genetics; Max Planck Institute for the Physics of Complex Systems; Center for Systems Biology; Max Planck Institute for Psycholinguistics; Australian National University; University of Oxford; Stony Brook University; John Jay College of Criminal Justice; University of Bristol; Max Planck Institute of Animal Behavior; University of Konstanz; Smithsonian Tropical Research Institute; University of Montpellier; University of Greifswald; The Rockefeller University; Howard Hughes Medical Institute; Donders Institute for Brain, Cognition and Behaviour; and Technical University Dresden.