Publications by authors named "Huabin Zhao"

46 Publications

ACE2 receptor usage reveals variation in susceptibility to SARS-CoV and SARS-CoV-2 infection among bat species.

Nat Ecol Evol 2021 Mar 1. Epub 2021 Mar 1.

State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.

Bats are the suggested natural hosts for severe acute respiratory syndrome coronavirus (SARS-CoV) and the causal agent of the coronavirus disease 2019 (COVID-19) pandemic, SARS-CoV-2. The interaction of viral spike proteins with their host receptor angiotensin-converting enzyme 2 (ACE2) is a critical determinant of potential hosts and cross-species transmission. Here we use virus-host receptor binding and infection assays to examine 46 ACE2 orthologues from phylogenetically diverse bat species, including those in close and distant contact with humans. We found that 24, 21 and 16 of them failed to support infection by SARS-CoV, SARS-CoV-2 or both viruses, respectively. Furthermore, we confirmed that infection assays in human cells were consistent with those in two bat cell lines. Additionally, we used genetic and functional analyses to identify critical residues in bat ACE2 receptors associated with viral entry restrictions. Our results suggest that many bat species may not be the potential hosts of one or both viruses and that no correlation was identified between proximity to humans and probability of being natural hosts of SARS-CoV or SARS-CoV-2. This study demonstrates dramatic variation in susceptibility to SARS-CoV and SARS-CoV-2 infection among bat species and adds knowledge towards a better understanding of coronavirus-bat interaction.
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http://dx.doi.org/10.1038/s41559-021-01407-1DOI Listing
March 2021

Loss of sweet taste despite the conservation of sweet receptor genes in insectivorous bats.

Proc Natl Acad Sci U S A 2021 Jan;118(4)

Department of Ecology, Tibetan Centre for Ecology and Conservation at Wuhan University-Tibet University, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, 430072 Wuhan, China;

The evolution of taste perception is usually associated with the ecology and dietary changes of organisms. However, the association between feeding ecology and taste receptor evolution is unclear in some lineages of vertebrate animals. One example is the sweet taste receptor gene Previous analysis of partial sequences has revealed that has undergone equally strong purifying selection between insectivorous and frugivorous bats. To test whether the sweet taste function is also important in bats with contrasting diets, we examined the complete coding sequences of both sweet taste receptor genes ( and ) in 34 representative bat species. Although these two genes are highly conserved between frugivorous and insectivorous bats at the sequence level, our behavioral experiments revealed that an insectivorous bat () showed no preference for natural sugars, whereas the frugivorous species () showed strong preferences for sucrose and fructose. Furthermore, while both sweet taste receptor genes are expressed in the taste tissue of insectivorous and frugivorous bats, our cell-based assays revealed striking functional divergence: the sweet taste receptors of frugivorous bats are able to respond to natural sugars whereas those of insectivorous bats are not, which is consistent with the behavioral preference tests, suggesting that functional evolution of sweet taste receptors is closely related to diet. This comprehensive study suggests that using sequence conservation alone could be misleading in inferring protein and physiological function and highlights the power of combining behavioral experiments, expression analysis, and functional assays in molecular evolutionary studies.
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http://dx.doi.org/10.1073/pnas.2021516118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848599PMC
January 2021

Molecular evolution and deorphanization of bitter taste receptors in a vampire bat.

Integr Zool 2020 Dec 2. Epub 2020 Dec 2.

Department of Ecology, Tibetan Centre for Ecology and Conservation at WHU-TU, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China.

Bats represent the largest dietary radiation in a single mammalian order, and have become an emerging model group for studying dietary evolution. Taste receptor genes have proven to be molecular signatures of dietary diversification in bats. For example, all 3 extant species of vampire bats have lost many bitter taste receptor genes (Tas2rs) in association with their dietary shift from insectivory to sanguivory. Indeed, only 8 full-length Tas2rs were identified from the high-quality genome of the common vampire bat (Desmodus rotundus). However, it is presently unknown whether these bitter receptors are functional, since the sense of taste is less important in vampire bats, which have an extremely narrow diet and rely on other senses for acquiring food. Here, we applied a molecular evolutionary analysis of Tas2rs in the common vampire bat compared with non-vampire bats. Furthermore, we provided the first attempt to deorphanize all bitter receptors of the vampire bat using a cell-based assay. We found that all Tas2r genes in the vampire bat have a level of selective pressure similar to that in non-vampire bats, suggesting that this species must have retained some bitter taste functions. We demonstrated that 5 of the 8 bitter receptors in the vampire bat can be activated by some bitter compounds, and observed that the vampire bat generally can not detect naturally occurring bitter compounds examined in this study. Our study demonstrates functional retention of bitter taste in vampire bats as suggested by cell-based functional assays, calling for an in-depth study of extra-oral functions of bitter taste receptors.
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http://dx.doi.org/10.1111/1749-4877.12509DOI Listing
December 2020

Genomic Analyses Reveal Genetic Adaptations to Tropical Climates in Chickens.

iScience 2020 Nov 3;23(11):101644. Epub 2020 Oct 3.

Department of Ecology, Tibetan Centre for Ecology and Conservation at WHU-TU, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, 299 Bayi Road, Wuhan, Hubei 430072, China.

The genetic footprints of adaptations to naturally occurring tropical stress along with domestication are poorly reported in chickens. Here, by conducting population genomic analyses of 67 chickens inhabiting distinct climates, we found signals of gene flow from Tibetan chickens to Sri Lankan and Saudi Arabian breeds and identified 12 positively selected genes that are likely involved in genetic adaptations to both tropical desert and tropical monsoon island climates. Notably, in tropical desert climate, advantageous alleles of and , which could inhibit replication of viruses in cells, suggest immune adaptation to the defense against zoonotic diseases in chickens. Furthermore, comparative genomic analysis showed that four genes (, , and ) involved in arachidonic acid metabolism have undergone convergent adaptation to tropical desert climate between birds and mammals. Our study offers insights into the genetic mechanisms of adaptations to tropical climates in birds and other animals and provides practical value for breeding design and medical research on avian viruses.
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http://dx.doi.org/10.1016/j.isci.2020.101644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578744PMC
November 2020

Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates.

Proc Natl Acad Sci U S A 2020 09 21;117(36):22311-22322. Epub 2020 Aug 21.

The Genome Center, University of California, Davis, CA 95616;

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of COVID-19. The main receptor of SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), is now undergoing extensive scrutiny to understand the routes of transmission and sensitivity in different species. Here, we utilized a unique dataset of ACE2 sequences from 410 vertebrate species, including 252 mammals, to study the conservation of ACE2 and its potential to be used as a receptor by SARS-CoV-2. We designed a five-category binding score based on the conservation properties of 25 amino acids important for the binding between ACE2 and the SARS-CoV-2 spike protein. Only mammals fell into the medium to very high categories and only catarrhine primates into the very high category, suggesting that they are at high risk for SARS-CoV-2 infection. We employed a protein structural analysis to qualitatively assess whether amino acid changes at variable residues would be likely to disrupt ACE2/SARS-CoV-2 spike protein binding and found the number of predicted unfavorable changes significantly correlated with the binding score. Extending this analysis to human population data, we found only rare (frequency <0.001) variants in 10/25 binding sites. In addition, we found significant signals of selection and accelerated evolution in the ACE2 coding sequence across all mammals, and specific to the bat lineage. Our results, if confirmed by additional experimental data, may lead to the identification of intermediate host species for SARS-CoV-2, guide the selection of animal models of COVID-19, and assist the conservation of animals both in native habitats and in human care.
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http://dx.doi.org/10.1073/pnas.2010146117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486773PMC
September 2020

Molecular adaptation and convergent evolution of frugivory in Old World and neotropical fruit bats.

Mol Ecol 2020 11 20;29(22):4366-4381. Epub 2020 Jul 20.

Department of Ecology, Tibetan Centre for Ecology and Conservation at WHU-TU, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China.

Although cases of independent adaptation to the same dietary niche have been documented in mammalian ecology, the molecular correlates of such shifts are seldom known. Here, we used genomewide analyses of molecular evolution to examine two lineages of bats that, from an insectivorous ancestor, have both independently evolved obligate frugivory: the Old World family Pteropodidae and the neotropical subfamily Stenodermatinae. New genome assemblies from two neotropical fruit bats (Artibeus jamaicensis and Sturnira hondurensis) provide a framework for comparisons with Old World fruit bats. Comparative genomics of 10 bat species encompassing dietary diversity across the phylogeny revealed convergent molecular signatures of frugivory in both multigene family evolution and single-copy genes. Evidence for convergent molecular adaptations associated with frugivorous diets includes the composition of three subfamilies of olfactory receptor genes, losses of three bitter taste receptor genes, losses of two digestive enzyme genes and convergent amino acid substitutions in several metabolic genes. By identifying suites of adaptations associated with the convergent evolution of frugivory, our analyses both reveal the extent of molecular mechanisms under selection in dietary shifts and will facilitate future studies of molecular ecology in mammals.
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http://dx.doi.org/10.1111/mec.15542DOI Listing
November 2020

Broad Host Range of SARS-CoV-2 Predicted by Comparative and Structural Analysis of ACE2 in Vertebrates.

bioRxiv 2020 Apr 18. Epub 2020 Apr 18.

The Genome Center, University of California Davis, Davis, CA 95616, USA.

The novel coronavirus SARS-CoV-2 is the cause of Coronavirus Disease-2019 (COVID-19). The main receptor of SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), is now undergoing extensive scrutiny to understand the routes of transmission and sensitivity in different species. Here, we utilized a unique dataset of 410 vertebrates, including 252 mammals, to study cross-species conservation of ACE2 and its likelihood to function as a SARS-CoV-2 receptor. We designed a five-category ranking score based on the conservation properties of 25 amino acids important for the binding between receptor and virus, classifying all species from to . Only mammals fell into the to categories, and only catarrhine primates in the category, suggesting that they are at high risk for SARS-CoV-2 infection. We employed a protein structural analysis to qualitatively assess whether amino acid changes at variable residues would be likely to disrupt ACE2/SARS-CoV-2 binding, and found the number of predicted unfavorable changes significantly correlated with the binding score. Extending this analysis to human population data, we found only rare (<0.1%) variants in 10/25 binding sites. In addition, we observed evidence of positive selection in ACE2 in multiple species, including bats. Utilized appropriately, our results may lead to the identification of intermediate host species for SARS-CoV-2, justify the selection of animal models of COVID-19, and assist the conservation of animals both in native habitats and in human care.
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http://dx.doi.org/10.1101/2020.04.16.045302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263403PMC
April 2020

COVID-19 drives new threat to bats in China.

Authors:
Huabin Zhao

Science 2020 03;367(6485):1436

Department of Ecology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.

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http://dx.doi.org/10.1126/science.abb3088DOI Listing
March 2020

Systematic analysis of the Hippo pathway organization and oncogenic alteration in evolution.

Sci Rep 2020 02 21;10(1):3173. Epub 2020 Feb 21.

Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, 92697, USA.

The Hippo pathway is a central regulator of organ size and a key tumor suppressor via coordinating cell proliferation and death. Initially discovered in Drosophila, the Hippo pathway has been implicated as an evolutionarily conserved pathway in mammals; however, how this pathway was evolved to be functional from its origin is still largely unknown. In this study, we traced the Hippo pathway in premetazoan species, characterized the intrinsic functions of its ancestor components, and unveiled the evolutionary history of this key signaling pathway from its unicellular origin. In addition, we elucidated the paralogous gene history for the mammalian Hippo pathway components and characterized their cancer-derived somatic mutations from an evolutionary perspective. Taken together, our findings not only traced the conserved function of the Hippo pathway to its unicellular ancestor components, but also provided novel evolutionary insights into the Hippo pathway organization and oncogenic alteration.
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http://dx.doi.org/10.1038/s41598-020-60120-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035326PMC
February 2020

Competitive oxidation and ubiquitylation on the evolutionarily conserved cysteine confer tissue-specific stabilization of Insig-2.

Nat Commun 2020 01 17;11(1):379. Epub 2020 Jan 17.

Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, 430072, China.

Insig-2 is an ER membrane protein negatively controlling lipid biosynthesis. Here, we find that Insig-2 is increased in the tissues, including liver, but unaltered in the muscle of gp78-deficient mice. In hepatocytes and undifferentiated C2C12 myoblasts, Insig-2 is ubiquitylated on Cys215 by gp78 and degraded. However, the C215 residue is oxidized by elevated reactive oxygen species (ROS) during C2C12 myoblasts differentiating into myotubes, preventing Insig-2 from ubiquitylation and degradation. The stabilized Insig-2 downregulates lipogenesis through inhibiting the SREBP pathway, helping to channel the carbon flux to ATP generation and protecting myotubes from lipid over-accumulation. Evolutionary analysis shows that the YECK (in which C represents Cys215 in human Insig-2) tetrapeptide sequence in Insig-2 is highly conserved in amniotes but not in aquatic amphibians and fishes, suggesting it may have been shaped by differential selection. Together, this study suggests that competitive oxidation-ubiquitylation on Cys215 of Insig-2 senses ROS and prevents muscle cells from lipid accumulation.
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http://dx.doi.org/10.1038/s41467-019-14231-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969111PMC
January 2020

Diet and Adaptive Evolution of Alanine-Glyoxylate Aminotransferase Mitochondrial Targeting in Birds.

Mol Biol Evol 2020 03;37(3):786-798

Department of Ecology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China.

Adaptations to different diets represent a hallmark of animal diversity. The diets of birds are highly variable, making them an excellent model system for studying adaptive evolution driven by dietary changes. To test whether molecular adaptations to diet have occurred during the evolution of birds, we examined a dietary enzyme alanine-glyoxylate aminotransferase (AGT), which tends to target mitochondria in carnivorous mammals, peroxisomes in herbivorous mammals, and both mitochondria and peroxisomes in omnivorous mammals. A total of 31 bird species were examined in this study, which included representatives of most major avian lineages. Of these, 29 have an intact mitochondrial targeting sequence (MTS) of AGT. This finding is in stark contrast to mammals, which showed a number of independent losses of the MTS. Our cell-based functional assays revealed that the efficiency of AGT mitochondrial targeting was greatly reduced in unrelated lineages of granivorous birds, yet it tended to be high in insectivorous and carnivorous lineages. Furthermore, we found that proportions of animal tissue in avian diets were positively correlated with mitochondrial targeting efficiencies that were experimentally determined, but not with those that were computationally predicted. Adaptive evolution of AGT mitochondrial targeting in birds was further supported by the detection of positive selection on MTS regions. Our study contributes to the understanding of how diet drives molecular adaptations in animals, and suggests that caution must be taken when computationally predicting protein subcellular targeting.
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http://dx.doi.org/10.1093/molbev/msz266DOI Listing
March 2020

Functional divergence of bitter taste receptors in a nectar-feeding bird.

Biol Lett 2019 09 25;15(9):20190461. Epub 2019 Sep 25.

Department of Ecology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan 430072, People's Republic of China.

Nectar may contain many secondary metabolites that are commonly toxic and bitter-tasting. It has been hypothesized that such bitter-tasting secondary metabolites might keep the nectar exclusive to only a few pollinators. To test this hypothesis, we examined functional changes of bitter taste receptor genes (s) in a species of nectar-feeding bird (Anna's hummingbird) by comparing these genes with those from two closely related insect-feeding species (chimney swift and chuck-will's widow). We previously identified a larger number of s in the hummingbird than in its close insectivorous relatives. In the present study, we demonstrate higher sensitivity and new functions in the hummingbird gene copies generated by a lineage-specific duplication, which has been shaped by positive selection. These results suggest that the bitter taste may lead to increased sensitivities and specialized abilities of the hummingbird to detect bitter-tasting nectar. Moreover, this study potentially supports the hypothesis that bitter-tasting nectar may have been specialized for some pollinators, thus enforcing plant-pollinator mutualism.
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http://dx.doi.org/10.1098/rsbl.2019.0461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769140PMC
September 2019

Convergent reduction of V1R genes in subterranean rodents.

BMC Evol Biol 2019 08 30;19(1):176. Epub 2019 Aug 30.

Department of Ecology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, 299 Bayi Road, Wuhan, 430072, Hubei, China.

Background: Vomeronasal type 1 receptor genes (V1Rs) are expected to detect intraspecific pheromones. It is believed that rodents rely heavily on pheromonal communication mediated by V1Rs, but pheromonal signals are thought to be confined in subterranean rodents that live in underground burrows. Thus, subterranean rodents may show a contrasting mode of V1R evolution compared with their superterranean relatives.

Results: We examined the V1R evolution in subterranean rodents by analyzing currently available genomes of 24 rodents, including 19 superterranean and 5 subterranean species from three independent lineages. We identified a lower number of putatively functional V1R genes in each subterranean rodent (a range of 22-40) compared with superterranean species (a range of 63-221). After correcting phylogenetic inertia, the positive correlation remains significant between the small V1R repertoire size and the subterranean lifestyle. To test whether V1Rs have been relaxed from functional constraints in subterranean rodents, we sequenced 22 intact V1Rs in 29 individuals of one subterranean rodent (Spalax galili) from two soil populations, which have been proposed to undergo incipient speciation. We found 12 of the 22 V1Rs to show significant genetic differentiations between the two natural populations, indicative of diversifying selection.

Conclusion: Our study demonstrates convergent reduction of V1Rs in subterranean rodents from three independent lineages. Meanwhile, it is noteworthy that most V1Rs in the two Spalax populations are under diversifying selection rather than relaxed selection, suggesting that functional constraints on these genes may have retained in some subterranean species.
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http://dx.doi.org/10.1186/s12862-019-1502-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717356PMC
August 2019

Origin and evolution of the major histocompatibility complex class I region in eutherian mammals.

Ecol Evol 2019 Jul 14;9(13):7861-7874. Epub 2019 Jun 14.

Department of Ecology, Hubei Key Laboratory of Cell Homeostasis, College of Life Science Wuhan University Wuhan China.

Major histocompatibility complex (MHC) genes in vertebrates are vital in defending against pathogenic infections. To gain new insights into the evolution of MHC Class I (MHCI) genes and test competing hypotheses on the origin of the MHCI region in eutherian mammals, we studied available genome assemblies of nine species in Afrotheria, Xenarthra, and Laurasiatheria, and successfully characterized the MHCI region in six species. The following numbers of putatively functional genes were detected: in the elephant, four, one, and eight in the extended class I region, and κ and β duplication blocks, respectively; in the tenrec, one in the κ duplication block; and in the four bat species, one or two in the β duplication block. Our results indicate that MHCI genes in the κ and β duplication blocks may have originated in the common ancestor of eutherian mammals. In the elephant, tenrec, and all four bats, some MHCI genes occurred outside the MHCI region, suggesting that eutherians may have a more complex MHCI genomic organization than previously thought. Bat-specific three- or five-amino-acid insertions were detected in the MHCI α1 domain in all four bats studied, suggesting that pathogen defense in bats relies on MHCIs having a wider peptide-binding groove, as previously assayed by a bat MHCI gene with a three-amino-acid insertion showing a larger peptide repertoire than in other mammals. Our study adds to knowledge on the diversity of eutherian MHCI genes, which may have been shaped in a taxon-specific manner.
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http://dx.doi.org/10.1002/ece3.5373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636196PMC
July 2019

Trehalase Gene as a Molecular Signature of Dietary Diversification in Mammals.

Mol Biol Evol 2019 10;36(10):2171-2183

Department of Ecology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China.

Diet is a key factor in determining and structuring animal diversity and adaptive radiations. The mammalian fossil record preserves phenotypic evidence of many dietary shifts, whereas genetic changes followed by dietary diversification in mammals remain largely unknown. To test whether living mammals preserve molecular evidence of dietary shifts, we examined the trehalase gene (Treh), which encodes an enzyme capable of digesting trehalose from insect blood, in bats and other mammals with diverse diets. Bats represent the largest dietary radiation among all mammalian orders, with independent origins of frugivory, nectarivory, carnivory, omnivory, and even sanguivory in an otherwise insectivorous clade. We found that Treh has been inactivated in unrelated bat lineages that independently radiated into noninsectivorous niches. Consistently, purifying selection has been markedly relaxed in noninsectivorous bats compared with their insectivorous relatives. Enzymatic assays of intestinal trehalase in bats suggest that trehalase activity tends to be lost or markedly reduced in noninsectivorous bats compared with their insectivorous relatives. Furthermore, our survey of Treh in 119 mammal species, which represent a deeper evolutionary timeframe, additionally identified a number of other independent losses of Treh in noninsectivorous species, recapitulating the evolutionary pattern that we found in bats. These results document a molecular record of dietary diversification in mammals, and suggest that such molecular signatures of dietary shifts would help us understand both historical and modern changes of animal diets.
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http://dx.doi.org/10.1093/molbev/msz127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759077PMC
October 2019

Sam50-Mic19-Mic60 axis determines mitochondrial cristae architecture by mediating mitochondrial outer and inner membrane contact.

Cell Death Differ 2020 01 16;27(1):146-160. Epub 2019 May 16.

Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072, China.

Mitochondrial cristae are critical for efficient oxidative phosphorylation, however, how cristae architecture is precisely organized remains largely unknown. Here, we discovered that Mic19, a core component of MICOS (mitochondrial contact site and cristae organizing system) complex, can be cleaved at N-terminal by mitochondrial protease OMA1 under certain physiological stresses. Mic19 directly interacts with mitochondrial outer-membrane protein Sam50 (the key subunit of SAM complex) and inner-membrane protein Mic60 (the key component of MICOS complex) to form Sam50-Mic19-Mic60 axis, which dominantly connects SAM and MICOS complexes to assemble MIB (mitochondrial intermembrane space bridging) supercomplex for mediating mitochondrial outer- and inner-membrane contact. OMA1-mediated Mic19 cleavage causes Sam50-Mic19-Mic60 axis disruption, which separates SAM and MICOS and leads to MIB disassembly. Disrupted Sam50-Mic19-Mic60 axis, even in the presence of SAM and MICOS complexes, causes the abnormal mitochondrial morphology, loss of mitochondrial cristae junctions, abnormal cristae distribution and reduced ATP production. Importantly, Sam50 displays punctate distribution at mitochondrial outer membrane, and acts as an anchoring point to guide the formation of mitochondrial cristae junctions. Therefore, we propose that Sam50-Mic19-Mic60 axis-mediated SAM-MICOS complexes integration determines mitochondrial cristae architecture.
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http://dx.doi.org/10.1038/s41418-019-0345-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206006PMC
January 2020

Evolution of digestive enzymes and dietary diversification in birds.

PeerJ 2019 25;7:e6840. Epub 2019 Apr 25.

Department of Ecology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China.

As the most species-rich class of tetrapod vertebrates, Aves possesses diverse feeding habits, with multiple origins of insectivory, carnivory, frugivory, nectarivory, granivory and omnivory. Since digestive enzymes mediate and limit energy and nutrient uptake, we hypothesized that genes encoding digestive enzymes have undergone adaptive evolution in birds. To test this general hypothesis, we identified 16 digestive enzyme genes (including seven carbohydrase genes (hepatic , pancreatic , salivary , , , and ), three lipase genes ( and ), two protease genes ( and ), two lysozyme genes ( and ) and two chitinase genes ( and )) from the available genomes of 48 bird species. Among these 16 genes, three (salivary , and ) were not found in all 48 avian genomes, which was further supported by our synteny analysis. Of the remaining 13 genes, eight were single-copy and five (, , , and ) were multi-copy. Moreover, the multi-copy genes , and were predicted to exhibit functional divergence among copies. Positively selected sites were detected in all of the analyzed digestive enzyme genes, except , , and , suggesting that different diets may have favored differences in catalytic capacities of these enzymes. Furthermore, the analysis also revealed that the pancreatic amylase gene and one of the lipase genes () have higher (the ratio of nonsynonymous to the synonymous substitution rates) values in species consuming a larger amount of seeds and meat, respectively, indicating an intense selection. In addition, the carbohydrase gene in species consuming a smaller amount of seeds, fruits or nectar, and a lipase gene () in species consuming less meat were found to be under relaxed selection. Thus, gene loss, gene duplication, functional divergence, positive selection and relaxed selection have collectively shaped the evolution of digestive enzymes in birds, and the evolutionary flexibility of these enzymes may have facilitated their dietary diversification.
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http://dx.doi.org/10.7717/peerj.6840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487185PMC
April 2019

Metal Ions Activate the Human Taste Receptor TAS2R7.

Chem Senses 2019 05;44(5):339-347

Monell Chemical Senses Center, Philadelphia, PA.

Divalent and trivalent salts exhibit a complex taste profile. They are perceived as being astringent/drying, sour, bitter, and metallic. We hypothesized that human bitter-taste receptors may mediate some taste attributes of these salts. Using a cell-based functional assay, we found that TAS2R7 responds to a broad range of divalent and trivalent salts, including zinc, calcium, magnesium, copper, manganese, and aluminum, but not to potassium, suggesting TAS2R7 may act as a metal cation receptor mediating bitterness of divalent and trivalent salts. Molecular modeling and mutagenesis analysis identified 2 residues, H943.37 and E2647.32, in TAS2R7 that appear to be responsible for the interaction of TAS2R7 with metallic ions. Taste receptors are found in both oral and extraoral tissues. The responsiveness of TAS2R7 to various mineral salts suggests it may act as a broad sensor, similar to the calcium-sensing receptor, for biologically relevant metal cations in both oral and extraoral tissues.
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http://dx.doi.org/10.1093/chemse/bjz024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538953PMC
May 2019

As Blind as a Bat? Opsin Phylogenetics Illuminates the Evolution of Color Vision in Bats.

Mol Biol Evol 2019 01;36(1):54-68

UCD School of Biology and Environmental Science, University College Dublin, Dublin 4, Ireland.

Through their unique use of sophisticated laryngeal echolocation bats are considered sensory specialists amongst mammals and represent an excellent model in which to explore sensory perception. Although several studies have shown that the evolution of vision is linked to ecological niche adaptation in other mammalian lineages, this has not yet been fully explored in bats. Recent molecular analysis of the opsin genes, which encode the photosensitive pigments underpinning color vision, have implicated high-duty cycle (HDC) echolocation and the adoption of cave roosting habits in the degeneration of color vision in bats. However, insufficient sampling of relevant taxa has hindered definitive testing of these hypotheses. To address this, novel sequence data was generated for the SWS1 and MWS/LWS opsin genes and combined with existing data to comprehensively sample species representing diverse echolocation types and niches (SWS1 n = 115; MWS/LWS n = 45). A combination of phylogenetic analysis, ancestral state reconstruction, and selective pressure analyses were used to reconstruct the evolution of these visual pigments in bats and revealed that although both genes are evolving under purifying selection in bats, MWS/LWS is highly conserved but SWS1 is highly variable. Spectral tuning analyses revealed that MWS/LWS opsin is tuned to a long wavelength, 555-560 nm in the bat ancestor and the majority of extant taxa. The presence of UV vision in bats is supported by our spectral tuning analysis, but phylogenetic analyses demonstrated that the SWS1 opsin gene has undergone pseudogenization in several lineages. We do not find support for a link between the evolution of HDC echolocation and the pseudogenization of the SWS1 gene in bats, instead we show the SWS1 opsin is functional in the HDC echolocator, Pteronotus parnellii. Pseudogenization of the SWS1 is correlated with cave roosting habits in the majority of pteropodid species. Together these results demonstrate that the loss of UV vision in bats is more widespread than was previously considered and further elucidate the role of ecological niche specialization in the evolution of vision in bats.
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http://dx.doi.org/10.1093/molbev/msy192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340466PMC
January 2019

Lineage-specific duplication and adaptive evolution of bitter taste receptor genes in bats.

Mol Ecol 2018 11 3;27(22):4475-4488. Epub 2018 Nov 3.

Department of Ecology and Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China.

By generating raw genetic material and diverse biological functions, gene duplication represents a major evolutionary mechanism that is of fundamental importance in ecological adaptation. The lineage-specific duplication events of bitter taste receptor genes (Tas2rs) have been identified in a number of vertebrates, but functional evolution of new Tas2r copies after duplication remains largely unknown. Here, we present the largest data set of bat Tas2rs to date, identified from existing genome sequences of 15 bat species and newly sequenced from 17 bat species, and demonstrate lineage-specific duplications of Tas2r16, Tas2r18 and Tas2r41 that only occurred in Myotis bats. Myotis bats are highly speciose and represent the only mammalian genus that is naturally distributed on every continent except Antarctica. The occupation of such diverse habitats might have driven the Tas2r gene expansion. New copies of Tas2rs in Myotis bats have shown molecular adaptation and functional divergence. For example, three copies of Tas2r16 in Myotis davidii showed differential sensitivities to arbutin and salicin that may occur in their insect prey, as suggested by cell-based functional assays. We hypothesize that functional differences among Tas2r copies in Myotis bats would increase their survival rate through preventing the ingestion of an elevated number of bitter-tasting dietary toxins from their insect prey, which may have facilitated their adaptation to diverse habitats. Our study demonstrates functional changes of new Tas2r copies after lineage-specific duplications in Myotis bats and highlights the potential role of taste perception in exploiting new environments.
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http://dx.doi.org/10.1111/mec.14873DOI Listing
November 2018

Testing the sensory trade-off hypothesis in New World bats.

Proc Biol Sci 2018 08 29;285(1885). Epub 2018 Aug 29.

Department of Ecology and Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan 430072, People's Republic of China

Detection of evolutionary shifts in sensory systems is challenging. By adopting a molecular approach, our earlier study proposed a sensory trade-off hypothesis between a loss of colour vision and an origin of high-duty-cycle (HDC) echolocation in Old World bats. Here, we test the hypothesis in New World bats, which include HDC echolocators that are distantly related to Old World HDC echolocators, as well as vampire bats, which have an infrared sensory system apparently unique among bats. Through sequencing the short-wavelength opsin gene () in 16 species (29 individuals) of New World bats, we identified a novel polymorphism in an HDC echolocator: one allele is pseudogenized but the other is intact, while both alleles are either intact or pseudogenized in other individuals. Strikingly, both alleles were found to be pseudogenized in all three vampire bats. Since pseudogenization, transcriptional or translational changes could separately result in functional loss of a gene, a pseudogenized indicates a loss of dichromatic colour vision in bats. Thus, the same sensory trade-off appears to have repeatedly occurred in the two divergent lineages of HDC echolocators, and colour vision may have also been traded off against the infrared sense in vampire bats.
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http://dx.doi.org/10.1098/rspb.2018.1523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125922PMC
August 2018

Intra and Interspecific Variations of Gene Expression Levels in Yeast Are Largely Neutral: (Nei Lecture, SMBE 2016, Gold Coast).

Mol Biol Evol 2017 09;34(9):2125-2139

Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI.

It is commonly, although not universally, accepted that most intra and interspecific genome sequence variations are more or less neutral, whereas a large fraction of organism-level phenotypic variations are adaptive. Gene expression levels are molecular phenotypes that bridge the gap between genotypes and corresponding organism-level phenotypes. Yet, it is unknown whether natural variations in gene expression levels are mostly neutral or adaptive. Here we address this fundamental question by genome-wide profiling and comparison of gene expression levels in nine yeast strains belonging to three closely related Saccharomyces species and originating from five different ecological environments. We find that the transcriptome-based clustering of the nine strains approximates the genome sequence-based phylogeny irrespective of their ecological environments. Remarkably, only ∼0.5% of genes exhibit similar expression levels among strains from a common ecological environment, no greater than that among strains with comparable phylogenetic relationships but different environments. These and other observations strongly suggest that most intra and interspecific variations in yeast gene expression levels result from the accumulation of random mutations rather than environmental adaptations. This finding has profound implications for understanding the driving force of gene expression evolution, genetic basis of phenotypic adaptation, and general role of stochasticity in evolution.
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http://dx.doi.org/10.1093/molbev/msx171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850415PMC
September 2017

Transcriptome sequencing and phylogenetic analysis of four species of luminescent beetles.

Sci Rep 2017 05 12;7(1):1814. Epub 2017 May 12.

Department of Ecology and Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, 430072, China.

The evolution of bioluminescence has prompted scientific attention to illuminate phylogenetic relationships of luminescent beetles. However, genomic resources are virtually lacking in rhagophthalmids (Rhagophthalmidae) and their related firefly beetles lampyrids (Lampyridae). Here, we employed the Illumina Hiseq 2000 platform and sequenced the whole-body transcriptomes of the four luminescent beetles: one rhagophthalmid (Rhagophthalmus sp.) and three fireflies (Asymmetricata circumdata, Aquatica ficta, and Pyrocoelia pectoralis). We obtained 55.4, 43.4, 38.6, and 36.7 million clean reads for the four species, respectively. All reads were assembled into contigs from which unigenes were derived. All unigenes were annotated by publicly available databases, and a total of 4325 orthologous genes were identified. Using multiple phylogenetic approaches, our transcriptome data confirmed the distinctiveness of Rhagophthalmidae from Lampyridae, which was also supported by our mitogenome analysis using three newly determined mitogenome sequences and 12 previously published ones. Together, this study is the first report of whole transcriptome sequencing data in Rhagophthalmidae and Lampyridae species, representing a valuable genomic resource for studying the origin and evolution of some remarkable traits in these beetles such as bioluminescence. Moreover, our transcriptome and mitogenome data provide useful phylogenetic information that could be of importance in future studies of phylogenetic inference.
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http://dx.doi.org/10.1038/s41598-017-01835-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431921PMC
May 2017

Two-Step Functional Innovation of the Stem-Cell Factors WUS/WOX5 during Plant Evolution.

Mol Biol Evol 2017 03;34(3):640-653

Institute for Advanced Studies, Wuhan University, Wuhan, China.

WUS and WOX5, which are expressed, respectively, in the organizing center (OC) and the quiescent center (QC), are essential for shoot/root apical stem-cell maintenance in flowering plants. However, little is known about how these stem-cell factors evolved their functions in flowering plants. Here, we show that the WUS/WOX5 proteins acquired two distinct capabilities by a two-step functional innovation process in the course of plant evolution. The first-step is the apical stem-cell maintenance activity of WUS/WOX5, which originated in the common ancestor of ferns and seed plants, as evidenced by the interspecies complementation experiments, showing that ectopic expression of fern Ceratopteris richardii WUS-like (CrWUL) surrounding OC/QC, or exclusive OC-/QC-expressed gymnosperms/angiosperms WUS/WOX5 in Arabidopsis wus-1 and wox5-1 mutants, could rescue their phenotypes. The second-step is the intercellular mobility that emerged in the common ancestor of seed plants after divergence from the ferns. Evidence for this includes confocal imaging of GFP fusion proteins, showing that WUS/WOX5 from seed plants, rather than from the fern CrWUL, can migrate into cells adjacent to the OC/QC. Evolutionary analysis showed that the WUS-like gene was duplicated into two copies prior to the divergence of gymnosperms/angiosperms. Then the two gene copies (WUS and WOX5) have undergone similar levels of purifying selection, which is consistent with their conserved functions in angiosperm shoot/root stem-cell maintenance and floral organ formation. Our results highlight the critical roles and the essential prerequisites that the two-step functional innovation of these genes performs and represents in the origin of flowering plants.
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http://dx.doi.org/10.1093/molbev/msw263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5400392PMC
March 2017

Penguins reduced olfactory receptor genes common to other waterbirds.

Sci Rep 2016 08 16;6:31671. Epub 2016 Aug 16.

Department of Ecology, College of Life Sciences, Wuhan University, Wuhan 430072, China.

The sense of smell, or olfaction, is fundamental in the life of animals. However, penguins (Aves: Sphenisciformes) possess relatively small olfactory bulbs compared with most other waterbirds such as Procellariiformes and Gaviiformes. To test whether penguins have a reduced reliance on olfaction, we analyzed the draft genome sequences of the two penguins, which diverged at the origin of the order Sphenisciformes; we also examined six closely related species with available genomes, and identified 29 one-to-one orthologous olfactory receptor genes (i.e. ORs) that are putatively functionally conserved and important across the eight birds. To survey the 29 one-to-one orthologous ORs in penguins and their relatives, we newly generated 34 sequences that are missing from the draft genomes. Through the analysis of totaling 378 OR sequences, we found that, of these functionally important ORs common to other waterbirds, penguins have a significantly greater percentage of OR pseudogenes than other waterbirds, suggesting a reduction of olfactory capability. The penguin-specific reduction of olfactory capability arose in the common ancestor of penguins between 23 and 60 Ma, which may have resulted from the aquatic specializations for underwater vision. Our study provides genetic evidence for a possible reduction of reliance on olfaction in penguins.
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http://dx.doi.org/10.1038/srep31671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4985648PMC
August 2016

Birds Generally Carry a Small Repertoire of Bitter Taste Receptor Genes.

Genome Biol Evol 2015 Sep 4;7(9):2705-15. Epub 2015 Sep 4.

Department of Ecology, College of Life Sciences, Wuhan University, Wuhan, China

As they belong to the most species-rich class of tetrapod vertebrates, birds have long been believed to possess an inferior taste system. However, the bitter taste is fundamental in birds to recognize dietary toxins (which are typically bitter) in potential food sources. To characterize the evolution of avian bitter taste receptor genes (Tas2rs) and to test whether dietary toxins have shaped the repertoire size of avian Tas2rs, we examined 48 genomes representing all but 3 avian orders. The total number of Tas2r genes was found to range from 1 in the domestic pigeon to 12 in the bar-tailed trogon, with an average of 4, which suggested that a much smaller Tas2r gene repertoire exists in birds than in other vertebrates. Furthermore, we uncovered a positive correlation between the number of putatively functional Tas2rs and the abundance of potential toxins in avian diets. Because plant products contain more toxins than animal tissues and insects release poisonous defensive secretions, we hypothesized that herbivorous and insectivorous birds may demand more functional Tas2rs than carnivorous birds feeding on noninsect animals. Our analyses appear to support this hypothesis and highlight the critical role of taste perception in birds.
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http://dx.doi.org/10.1093/gbe/evv180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4607536PMC
September 2015

Sympatric speciation revealed by genome-wide divergence in the blind mole rat Spalax.

Proc Natl Acad Sci U S A 2015 Sep 4;112(38):11905-10. Epub 2015 Sep 4.

Department of Ecology, College of Life Sciences, Wuhan University, Wuhan 430072, China;

Sympatric speciation (SS), i.e., speciation within a freely breeding population or in contiguous populations, was first proposed by Darwin [Darwin C (1859) On the Origins of Species by Means of Natural Selection] and is still controversial despite theoretical support [Gavrilets S (2004) Fitness Landscapes and the Origin of Species (MPB-41)] and mounting empirical evidence. Speciation of subterranean mammals generally, including the genus Spalax, was considered hitherto allopatric, whereby new species arise primarily through geographic isolation. Here we show in Spalax a case of genome-wide divergence analysis in mammals, demonstrating that SS in continuous populations, with gene flow, encompasses multiple widespread genomic adaptive complexes, associated with the sharply divergent ecologies. The two abutting soil populations of S. galili in northern Israel habituate the ancestral Senonian chalk population and abutting derivative Plio-Pleistocene basalt population. Population divergence originated ∼0.2-0.4 Mya based on both nuclear and mitochondrial genome analyses. Population structure analysis displayed two distinctly divergent clusters of chalk and basalt populations. Natural selection has acted on 300+ genes across the genome, diverging Spalax chalk and basalt soil populations. Gene ontology enrichment analysis highlights strong but differential soil population adaptive complexes: in basalt, sensory perception, musculature, metabolism, and energetics, and in chalk, nutrition and neurogenetics are outstanding. Population differentiation of chemoreceptor genes suggests intersoil population's mate and habitat choice substantiating SS. Importantly, distinctions in protein degradation may also contribute to SS. Natural selection and natural genetic engineering [Shapiro JA (2011) Evolution: A View From the 21st Century] overrule gene flow, evolving divergent ecological adaptive complexes. Sharp ecological divergences abound in nature; therefore, SS appears to be an important mode of speciation as first envisaged by Darwin [Darwin C (1859) On the Origins of Species by Means of Natural Selection].
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http://dx.doi.org/10.1073/pnas.1514896112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4586841PMC
September 2015

Genome-wide analysis of homeobox genes from Mesobuthus martensii reveals Hox gene duplication in scorpions.

Insect Biochem Mol Biol 2015 Jun 21;61:25-33. Epub 2015 Apr 21.

College of Life Sciences, Wuhan University, Wuhan, China. Electronic address:

Homeobox genes belong to a large gene group, which encodes the famous DNA-binding homeodomain that plays a key role in development and cellular differentiation during embryogenesis in animals. Here, one hundred forty-nine homeobox genes were identified from the Asian scorpion, Mesobuthus martensii (Chelicerata: Arachnida: Scorpiones: Buthidae) based on our newly assembled genome sequence with approximately 248 × coverage. The identified homeobox genes were categorized into eight classes including 82 families: 67 ANTP class genes, 33 PRD genes, 11 LIM genes, five POU genes, six SINE genes, 14 TALE genes, five CUT genes, two ZF genes and six unclassified genes. Transcriptome data confirmed that more than half of the genes were expressed in adults. The homeobox gene diversity of the eight classes is similar to the previously analyzed Mandibulata arthropods. Interestingly, it is hypothesized that the scorpion M. martensii may have two Hox clusters. The first complete genome-wide analysis of homeobox genes in Chelicerata not only reveals the repertoire of scorpion, arachnid and chelicerate homeobox genes, but also shows some insights into the evolution of arthropod homeobox genes.
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http://dx.doi.org/10.1016/j.ibmb.2015.04.002DOI Listing
June 2015

Molecular evidence for the loss of three basic tastes in penguins.

Curr Biol 2015 Feb;25(4):R141-2

Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, Michigan 48109, USA. Electronic address:

Sensing its biotic and abiotic environmental cues is critical to the survival and reproduction of any organism. Of the five traditionally recognized senses of vertebrates, taste is dedicated to the differentiation between nutritious and harmful foods, triggering either appetitive or rejective behaviors. Vertebrates typically can detect five basic taste qualities: sweet, umami, bitter, sour and salty. Remarkable progress in understanding the molecular basis of taste has opened the door to inferring taste abilities from genetic data. Based on genome and relevant gene sequences, we infer that the sweet, umami, and bitter tastes have been lost in all penguins, an order of aquatic flightless birds originating and still occupying the coldest ecological niche on Earth, the Antarctic.
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http://dx.doi.org/10.1016/j.cub.2015.01.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4333347PMC
February 2015

Vampire bats exhibit evolutionary reduction of bitter taste receptor genes common to other bats.

Proc Biol Sci 2014 Aug;281(1788):20141079

Department of Zoology, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China

The bitter taste serves as an important natural defence against the ingestion of poisonous foods and is thus believed to be indispensable in animals. However, vampire bats are obligate blood feeders that show a reduced behavioural response towards bitter-tasting compounds. To test whether bitter taste receptor genes (T2Rs) have been relaxed from selective constraint in vampire bats, we sampled all three vampire bat species and 11 non-vampire bats, and sequenced nine one-to-one orthologous T2Rs that are assumed to be functionally conserved in all bats. We generated 85 T2R sequences and found that vampire bats have a significantly greater percentage of pseudogenes than other bats. These results strongly suggest a relaxation of selective constraint and a reduction of bitter taste function in vampire bats. We also found that vampire bats retain many intact T2Rs, and that the taste signalling pathway gene Calhm1 remains complete and intact with strong functional constraint. These results suggest the presence of some bitter taste function in vampire bats, although it is not likely to play a major role in food selection. Together, our study suggests that the evolutionary reduction of bitter taste function in animals is more pervasive than previously believed, and highlights the importance of extra-oral functions of taste receptor genes.
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http://dx.doi.org/10.1098/rspb.2014.1079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4083806PMC
August 2014