Black fruit bats, Pteropus alecto |
Genomic Basis of Bat Superpowers Revealed: Like How They Survive Deadly Viruses | | SBU News
There is a sudden surge of interest in biological circles about bats and in particular why they are the source of so many deadly viral diseases, probably as a result of the Covid-19 pandemic and sciences attempt to understand it and find better treatments and a cure.
While I've been working on my next book, "The Malevolent Designer: Why Nature's God is not Good", a book also prompted by the Covid-19 pandemic, a couple of papers were published which suggest, if we accept for a moment the Creationist intelligent [sic] design argument, that their putative designer uses bats as laboratories for developing ever more deadly viruses such as SARS-CoV-2, the coronavirus which causes Covid-19, MERS, rabies and ebola.
More and more, we find gene duplications and losses as important processes in the evolution of new features and functions across the Tree of Life. But, determining when genes have duplicated is difficult if the genome is incomplete, and it is even harder to figure out if genes have been lost. At extremely high quality, the new bat genomes leave no doubts about changes in important gene families that could not be discovered otherwise with lower-quality genomes.
It appears that bats have unique immune systems, evolved in part by a loss of a family of genes, APOBEC3, that most mammals have as part of their immune systems. This was discovered by a Stony Brook University team who have produced the most detailed bat genomes to date from six widely divergent bat species.Professor Liliana M. Dávalos, co-author,
Department of Ecology and Evolution
College of Arts and Sciences
Stony Brook University.
Department of Ecology and Evolution
College of Arts and Sciences
Stony Brook University.
The team also discovered that bat genomes contain 'fossil' remnants of past viral infections in the junk DNA showing that bats have a history of association with viruses and of surviving previous infections. And they also showed that bats are most closely related to a group called Fereuungulata that consists of carnivorans (which includes dogs, cats and seals, among other species), pangolins, whales and ungulates (hooved mammals). The distant relationship to the pangolin is interesting, given that this species has been cited as a possible intermediate host for the coronavirus SARS-CoV before it finally mutated to give SARS-CoV-2.
This team published their work, open access in Nature.
Abstract
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 protocols1 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 disease1.
David Jebb, Zixia Huang, Martin Pippel, Graham M. Hughes, Ksenia Lavrichenko, Paolo Devanna, Sylke Winkler, Lars S. Jermiin, Emilia C. Skirmuntt, Aris Katzourakis, Lucy Burkitt-Gray, David A. Ray, Kevin A. M. Sullivan, Juliana G. Roscito, Bogdan M. Kirilenko, Liliana M. Dávalos, Angelique P. Corthals, Megan L. Power, Gareth Jones, Roger D. Ransome, Dina K. N. Dechmann, Andrea G. Locatelli, Sébastien J. Puechmaille, Olivier Fedrigo, Erich D. Jarvis, Michael Hiller, Sonja C. Vernes, Eugene W. Myers & Emma C. Teeling
Six reference-quality genomes reveal evolution of bat adaptations
Nature 583, 578–584 (2020) DOI: 10.1038/s41586-020-2486-3
Copyright: © 2020 The authors
Published by Springer Nature. Open access
Reprinted under a Creative Commons Attribution 4.0 International License (CC BY 4.0)
Cover of forthcoming book. Artwork by Catherine Hounslow |
There's Something Special About Bat Immunity That Makes Them Ideal Viral Incubators
The second paper adds to this work by going some way to explain how exactly bats can be vectors for so many viruses which are deadly to other mammals, including humans, yet remain relatively unharmed by them, although they are sometimes victims of the rabies virus they often carry. It was the work of a combined American and German team of researchers led by Cara E Brook of the Department of Integrative Biology, University of California, Berkeley, USA and of the Department of Ecology and Evolutionary Biology, Princeton University, Princeton, USA.
They used cell cultures from different bat lines to investigate the molecular response of cells to viruses. What they found was that some bats have a response permanently turned on that in most mammals only activates when the cell is infected. This means that bats react instantaneously, compared to the much slower response of most mammals. The response produces interferon which alerts neighbouring cells which can then prepare for an immune response. However, the drawback to having this switched on in most mammals is that it also produces an inflammatory response that can do more damage in the long run than the virus does. In the human response to SARS-CoV-2, for example, a prolonged production of interferon I and III is believed to do much of the long term damage and is a leading cause of death due to destruction of lungs and other organs.
This suggests that having a really robust interferon system would help these viruses persist within the host... When you have a higher immune response, you get these cells that are protected from infection, so the virus can actually ramp up its replication rate without causing damage to its host. But when it spills over into something like a human, we don't have those same sorts of antiviral mechanism, and we could experience a lot of pathology.
However, in bats, which appear to be able to cope with the inflammatory effects of interferon, the downside is that it doesn't kill the viruses, but allows them to live in the cells almost with impunity, where they can mutate in a process of natural selection in response to the bat's immune system. A process that almost seems designed to promote experimentation with new mutations to create ever-more infectious variants. Bats can thus act as repositories for these viruses while being a source of mutant, more infectious, forms of them.Cara Brook, lead author
Department of Integrative Biology
University of California, Berkeley, Berkeley, USA
Department of Integrative Biology
University of California, Berkeley, Berkeley, USA
This teams results are published open access in eLife:
Abstract
Bats host virulent zoonotic viruses without experiencing disease. A mechanistic understanding of the impact of bats’ virus hosting capacities, including uniquely constitutive immune pathways, on cellular-scale viral dynamics is needed to elucidate zoonotic emergence. We carried out virus infectivity assays on bat cell lines expressing induced and constitutive immune phenotypes, then developed a theoretical model of our in vitro system, which we fit to empirical data. Best fit models recapitulated expected immune phenotypes for representative cell lines, supporting robust antiviral defenses in bat cells that correlated with higher estimates for within-host viral propagation rates. In general, heightened immune responses limit pathogen-induced cellular morbidity, which can facilitate the establishment of rapidly-propagating persistent infections within-host. Rapidly-transmitting viruses that have evolved with bat immune systems will likely cause enhanced virulence following emergence into secondary hosts with immune systems that diverge from those unique to bats.
Cara E Brook, Mike Boots, Kartik Chandran, Andrew P Dobson, Christian Drosten, Andrea L Graham, Bryan T Grenfell, Marcel A Müller, Melinda Ng, Lin-Fa Wang, Anieke van Leeuwen
Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence
eLife 2020; 9:e48401 DOI: 10.7554/eLife.48401
Copyright: © 2020 The authors
Published by eLifeScience. Open access
Reprinted under a Creative Commons Attribution License 4.0 (CC BY 4.0)
So, creationists, what are we to make of this? Has your intelligent [sic] designer simply decided to give bats a superior immune system that it could have give us but prefers us to die of the nasty viruses that it produces, or has it set bats up to act as random generators of these lethal viruses by a process of evolution by natural selection in the environment of bats' bodies?
Or, rather than make your creator god look like a malevolent, misanthropic, genocidal sadist, would you prefer to attribute all this to a mindless, natural process of evolution by natural selection? This latter question will be posed over and over again in my forthcoming book, "The Malevolent Designer: Why Nature's God is not Good"
Your god; your choice.
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