Unraveling molecular mechanisms of immunity and cancer-resistance using the genomes of the Neotropical bats Artibeus jamaicensis and Pteronotus mesoamericanus

AbstractBats are exceptional among mammals for harbouring diverse pathogens and for their robust immune systems. In addition, bats are unusually long-lived and show low rates of cancer. Contiguous and complete reference genomes are needed to determine the genetic basis of these adaptations and establish bats as models for research into mammalian health. Here we sequenced and analysed the genomes of the Jamaican fruit bat (Artibeus jamaicensis) and the Mesoamerican mustached bat (Pteronotus mesoamericanus). We sequenced these two species using a mix of Illumina and Oxford Nanopore Technologies (ONT), assembling draft genomes with some of the highest contig N50s (28-29Mb) of bat genomes to date. Work is in progress to increase the base-level accuracies of these genomes. We conducted gene annotation and identified a set of 10,928 orthologs from bats and mammalian outgroups including humans, rodents, horses, pigs, and dogs. To detect positively selected genes as well as lineage-specific gene gains and losses, we carried out comprehensive branch-site likelihood ratio tests and gene family size analyses. Our analysis found signatures of rapid evolution in the innate immune response genes of bats, and evidence of past infections with diverse viral clades in Artibeus jamaicensis and Pteronotus mesoamericanus. We additionally found evidence of positive selection of tumor suppressors, which may play a role in the low cancer rates, in the most recent common ancestor of bats. These new genomic resources enable insights into the extraordinary adaptations of bats, with implications for mammalian evolutionary studies and public health.

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Ecoepidemiology and Complete Genome Comparison of Different Strains of Severe Acute Respiratory Syndrome-Related Rhinolophus Bat Coronavirus in China Reveal Bats as a Reservoir for Acute, Self-Limiting Infection That Allows Recombination Events

Journal of Virology ◽

10.1128/jvi.02219-09 ◽

2010 ◽

Vol 84 (6) ◽

pp. 2808-2819 ◽

Cited By ~ 149

Author(s):

Susanna K. P. Lau ◽

Kenneth S. M. Li ◽

Yi Huang ◽

Chung-Tong Shek ◽

Herman Tse ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Complete Genome ◽

Rapid Evolution ◽

Recent Common Ancestor ◽

Genome Comparison ◽

Most Recent Common Ancestor ◽

Body Weights ◽

Clock Analysis ◽

Different Strains ◽

Horseshoe Bats

ABSTRACT Despite the identification of severe acute respiratory syndrome-related coronavirus (SARSr-CoV) in Rhinolophus Chinese horseshoe bats (SARSr-Rh-BatCoV) in China, the evolutionary and possible recombination origin of SARSr-CoV remains undetermined. We carried out the first study to investigate the migration pattern and SARSr-Rh-BatCoV genome epidemiology in Chinese horseshoe bats during a 4-year period. Of 1,401 Chinese horseshoe bats from Hong Kong and Guangdong, China, that were sampled, SARSr-Rh-BatCoV was detected in alimentary specimens from 130 (9.3%) bats, with peak activity during spring. A tagging exercise of 511 bats showed migration distances from 1.86 to 17 km. Bats carrying SARSr-Rh-BatCoV appeared healthy, with viral clearance occurring between 2 weeks and 4 months. However, lower body weights were observed in bats positive for SARSr-Rh-BatCoV, but not Rh-BatCoV HKU2. Complete genome sequencing of 10 SARSr-Rh-BatCoV strains showed frequent recombination between different strains. Moreover, recombination was detected between SARSr-Rh-BatCoV Rp3 from Guangxi, China, and Rf1 from Hubei, China, in the possible generation of civet SARSr-CoV SZ3, with a breakpoint at the nsp16/spike region. Molecular clock analysis showed that SARSr-CoVs were newly emerged viruses with the time of the most recent common ancestor (tMRCA) at 1972, which diverged between civet and bat strains in 1995. The present data suggest that SARSr-Rh-BatCoV causes acute, self-limiting infection in horseshoe bats, which serve as a reservoir for recombination between strains from different geographical locations within reachable foraging range. Civet SARSr-CoV is likely a recombinant virus arising from SARSr-CoV strains closely related to SARSr-Rh-BatCoV Rp3 and Rf1. Such frequent recombination, coupled with rapid evolution especially in ORF7b/ORF8 region, in these animals may have accounted for the cross-species transmission and emergence of SARS.

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Rapid evolution of troglomorphic characters suggests selection rather than neutral mutation as a driver of eye reduction in cave crabs

Biology Letters ◽

10.1098/rsbl.2012.1098 ◽

2013 ◽

Vol 9 (2) ◽

pp. 20121098 ◽

Cited By ~ 28

Author(s):

Sebastian Klaus ◽

José C. E. Mendoza ◽

Jia Huan Liew ◽

Martin Plath ◽

Rudolf Meier ◽

...

Keyword(s):

Temporal Pattern ◽

Common Ancestor ◽

Rapid Evolution ◽

Genetic Distances ◽

Directional Selection ◽

Neutral Evolution ◽

Recent Common Ancestor ◽

Mitochondrial Markers ◽

Most Recent Common Ancestor ◽

Freshwater Crabs

This study asked whether reductive traits in cave organisms evolve at a slower pace (suggesting neutral evolution under relaxed selection) than constructive changes, which are likely to evolve under directional selection. We investigated 11 subterranean and seven surface populations of Sundathelphusa freshwater crabs on Bohol Island, Philippines, and examined constructive traits associated with improved food finding in darkness (increased leg and setae length) and reductive traits (reduced cornea size and eyestalk length). All changes occurred rapidly, given that the age of the most recent common ancestor was estimated to be 722–271 ka based on three mitochondrial markers. In order to quantify the speed of character change, we correlated the degree of morphological change with genetic distances between surface and subterranean individuals. The temporal pattern of character change following the transition to subterranean life was indistinguishable for constructive and reductive traits, characterized by an immediate onset and rapid evolutionary change. We propose that the evolution of these reductive traits—just like constructive traits—is most likely driven by strong directional selection.

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Pinpointing the PRDM9-PRDM7 Gene Duplication Event During Primate Divergence

Frontiers in Genetics ◽

10.3389/fgene.2021.593725 ◽

2021 ◽

Vol 12 ◽

Author(s):

Sacha Heerschop ◽

Zahra Fagrouch ◽

Ernst J. Verschoor ◽

Hans Zischler

Keyword(s):

Phylogenetic Tree ◽

Molecular Mechanisms ◽

Zinc Fingers ◽

Hybrid Sterility ◽

Duplication Event ◽

Model Systems ◽

Recent Common Ancestor ◽

Most Recent Common Ancestor ◽

Evolutionary Consequences ◽

Exon 10

Studies on the function of PRDM9 in model systems and its evolution during vertebrate divergence shed light on the basic molecular mechanisms of hybrid sterility and its evolutionary consequences. However, information regarding PRDM9-homolog, PRDM7, whose origin is placed in the primate evolutionary tree, as well as information about the fast-evolving DNA-binding zinc finger array of strepsirrhine PRDM9 are scarce. Thus, we aimed to narrow down the date of the duplication event leading to the emergence of PRDM7 during primate evolution by comparing the phylogenetic tree reconstructions of representative primate samples of PRDM orthologs and paralogs. To confirm our PRDM7 paralogization pattern, database-deposited sequences were used to test the presence/absence patterns expected from the paralogization timing. In addition, we extended the existing phylogenetic tree of haplorrhine PRDM9 zinc fingers with their strepsirrhine counterparts. The inclusion of strepsirrhine zinc fingers completes the PRDM9 primate phylogeny. Moreover, the updated phylogeny of PRDM9 zinc fingers showed distinct clusters of strepsirrhine, tarsier, and anthropoid degenerated zinc fingers. Here, we show that PRDM7 emerged on the branch leading to the most recent common ancestor of catarrhines; therefore, its origin is more recent than previously expected. A more detailed character evolutionary study suggests that PRDM7 may have evolved differently in Cercopithecoidea as compared to Hominoidea: it lacks the first four exons in Old World monkeys orthologs and exon 10 in Papionini orthologs. Dating the origin of PRDM7 is essential for further studies investigating why Hominoidea representatives need another putative histone methyltransferase in the testis.

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Allelic Genealogies in Sporophytic Self-Incompatibility Systems in Plants

Genetics ◽

10.1093/genetics/150.3.1187 ◽

1998 ◽

Vol 150 (3) ◽

pp. 1187-1198 ◽

Cited By ~ 9

Author(s):

Mikkel H Schierup ◽

Xavier Vekemans ◽

Freddy B Christiansen

Keyword(s):

Dominance Hierarchy ◽

Common Ancestor ◽

Recent Common Ancestor ◽

Self Incompatibility ◽

Most Recent Common Ancestor ◽

Dominance Interactions ◽

Turnover Process ◽

Neutral Gene ◽

Interspecific Comparisons ◽

Coalescence Times

Abstract Expectations for the time scale and structure of allelic genealogies in finite populations are formed under three models of sporophytic self-incompatibility. The models differ in the dominance interactions among the alleles that determine the self-incompatibility phenotype: In the SSIcod model, alleles act codominantly in both pollen and style, in the SSIdom model, alleles form a dominance hierarchy, and in SSIdomcod, alleles are codominant in the style and show a dominance hierarchy in the pollen. Coalescence times of alleles rarely differ more than threefold from those under gametophytic self-incompatibility, and transspecific polymorphism is therefore expected to be equally common. The previously reported directional turnover process of alleles in the SSIdomcod model results in coalescence times lower and substitution rates higher than those in the other models. The SSIdom model assumes strong asymmetries in allelic action, and the most recessive extant allele is likely to be the most recent common ancestor. Despite these asymmetries, the expected shape of the allele genealogies does not deviate markedly from the shape of a neutral gene genealogy. The application of the results to sequence surveys of alleles, including interspecific comparisons, is discussed.

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Molecular epidemiological characteristics of echovirus 6 in mainland China: extensive circulation of genotype F from 2007 to 2018

Archives of Virology ◽

10.1007/s00705-020-04934-7 ◽

2021 ◽

Author(s):

Wenjun Cheng ◽

Tianjiao Ji ◽

Shuaifeng Zhou ◽

Yong Shi ◽

Lili Jiang ◽

...

Keyword(s):

Common Ancestor ◽

Mainland China ◽

Recent Common Ancestor ◽

Genetic Characteristics ◽

Most Recent Common Ancestor ◽

Significant Difference ◽

Echovirus 6 ◽

Epidemiological Characteristics ◽

Highest Posterior Density ◽

Genotype F

AbstractEchovirus 6 (E6) is associated with various clinical diseases and is frequently detected in environmental sewage. Despite its high prevalence in humans and the environment, little is known about its molecular phylogeography in mainland China. In this study, 114 of 21,539 (0.53%) clinical specimens from hand, foot, and mouth disease (HFMD) cases collected between 2007 and 2018 were positive for E6. The complete VP1 sequences of 87 representative E6 strains, including 24 strains from this study, were used to investigate the evolutionary genetic characteristics and geographical spread of E6 strains. Phylogenetic analysis based on VP1 nucleotide sequence divergence showed that, globally, E6 strains can be grouped into six genotypes, designated A to F. Chinese E6 strains collected between 1988 and 2018 were found to belong to genotypes C, E, and F, with genotype F being predominant from 2007 to 2018. There was no significant difference in the geographical distribution of each genotype. The evolutionary rate of E6 was estimated to be 3.631 × 10-3 substitutions site-1 year-1 (95% highest posterior density [HPD]: 3.2406 × 10-3-4.031 × 10-3 substitutions site-1 year-1) by Bayesian MCMC analysis. The most recent common ancestor of the E6 genotypes was traced back to 1863, whereas their common ancestor in China was traced back to around 1962. A small genetic shift was detected in the Chinese E6 population size in 2009 according to Bayesian skyline analysis, which indicated that there might have been an epidemic around that year.

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Molecular epidemiology of coxsackievirus A16 circulating in children in Beijing, China from 2010 to 2019

World Journal of Pediatrics ◽

10.1007/s12519-021-00451-y ◽

2021 ◽

Author(s):

Ya-Fang Hu ◽

Li-Ping Jia ◽

Fang-Yuan Yu ◽

Li-Ying Liu ◽

Qin-Wei Song ◽

...

Keyword(s):

Molecular Epidemiology ◽

Evolutionary Rate ◽

Foot And Mouth Disease ◽

Recent Common Ancestor ◽

Rt Pcr ◽

Coxsackievirus A16 ◽

Most Recent Common Ancestor ◽

Etiological Agents ◽

High Level ◽

And Control

Abstract Background Coxsackievirus A16 (CVA16) is one of the major etiological agents of hand, foot and mouth disease (HFMD). This study aimed to investigate the molecular epidemiology and evolutionary characteristics of CVA16. Methods Throat swabs were collected from children with HFMD and suspected HFMD during 2010–2019. Enteroviruses (EVs) were detected and typed by real-time reverse transcription-polymerase chain reaction (RT-PCR) and RT-PCR. The genotype, evolutionary rate, the most recent common ancestor, population dynamics and selection pressure of CVA16 were analyzed based on viral protein gene (VP1) by bioinformatics software. Results A total of 4709 throat swabs were screened. EVs were detected in 3180 samples and 814 were CVA16 positive. More than 81% of CVA16-positive children were under 5 years old. The prevalence of CVA16 showed obvious periodic fluctuations with a high level during 2010–2012 followed by an apparent decline during 2013–2017. However, the activities of CVA16 increased gradually during 2018–2019. All the Beijing CVA16 strains belonged to sub-genotype B1, and B1b was the dominant strain. One B1c strain was detected in Beijing for the first time in 2016. The estimated mean evolutionary rate of VP1 gene was 4.49 × 10–3 substitution/site/year. Methionine gradually fixed at site-23 of VP1 since 2012. Two sites were detected under episodic positive selection, one of which (site-223) located in neutralizing linear epitope PEP71. Conclusions The dominant strains of CVA16 belonged to clade B1b and evolved in a fast evolutionary rate during 2010–2019 in Beijing. To provide more favorable data for HFMD prevention and control, it is necessary to keep attention on molecular epidemiological and evolutionary characteristics of CVA16.

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Transcriptome and metabolome profiling provide insights into molecular mechanism of pseudostem elongation in banana

BMC Plant Biology ◽

10.1186/s12870-021-02899-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Guiming Deng ◽

Fangcheng Bi ◽

Jing Liu ◽

Weidi He ◽

Chunyu Li ◽

...

Keyword(s):

Cell Wall ◽

Cell Elongation ◽

Molecular Mechanisms ◽

Specific Gene ◽

Wild Type ◽

Banana Plant ◽

Cell Wall Modification ◽

Dwarf Cultivar ◽

Important Trait ◽

Metabolome Profiling

AbstractBackgroundBanana plant height is an important trait for horticultural practices and semi-dwarf cultivars show better resistance to damages by wind and rain. However, the molecular mechanisms controlling the pseudostem height remain poorly understood. Herein, we studied the molecular changes in the pseudostem of a semi-dwarf banana mutant Aifen No. 1 (Musaspp. Pisang Awak sub-group ABB) as compared to its wild-type dwarf cultivar using a combined transcriptome and metabolome approach.ResultsA total of 127 differentially expressed genes and 48 differentially accumulated metabolites were detected between the mutant and its wild type. Metabolites belonging to amino acid and its derivatives, flavonoids, lignans, coumarins, organic acids, and phenolic acids were up-regulated in the mutant. The transcriptome analysis showed the differential regulation of genes related to the gibberellin pathway, auxin transport, cell elongation, and cell wall modification. Based on the regulation of gibberellin and associated pathway-related genes, we discussed the involvement of gibberellins in pseudostem elongation in the mutant banana. Genes and metabolites associated with cell wall were explored and their involvement in cell extension is discussed.ConclusionsThe results suggest that gibberellins and associated pathways are possibly developing the observed semi-dwarf pseudostem phenotype together with cell elongation and cell wall modification. The findings increase the understanding of the mechanisms underlying banana stem height and provide new clues for further dissection of specific gene functions.

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The Ancestry of a Sample of Sequences Subject to Recombination

Genetics ◽

10.1093/genetics/151.3.1217 ◽

1999 ◽

Vol 151 (3) ◽

pp. 1217-1228 ◽

Cited By ~ 1

Author(s):

Carsten Wiuf ◽

Jotun Hein

Keyword(s):

Genetic Distance ◽

Population Size ◽

Upper Bound ◽

Recombination Rate ◽

Common Ancestor ◽

Recent Common Ancestor ◽

Sequence Length ◽

Most Recent Common Ancestor ◽

The Mean ◽

Mean Time

Abstract In this article we discuss the ancestry of sequences sampled from the coalescent with recombination with constant population size 2N. We have studied a number of variables based on simulations of sample histories, and some analytical results are derived. Consider the leftmost nucleotide in the sequences. We show that the number of nucleotides sharing a most recent common ancestor (MRCA) with the leftmost nucleotide is ≈log(1 + 4N Lr)/4Nr when two sequences are compared, where L denotes sequence length in nucleotides, and r the recombination rate between any two neighboring nucleotides per generation. For larger samples, the number of nucleotides sharing MRCA with the leftmost nucleotide decreases and becomes almost independent of 4N Lr. Further, we show that a segment of the sequences sharing a MRCA consists in mean of 3/8Nr nucleotides, when two sequences are compared, and that this decreases toward 1/4Nr nucleotides when the whole population is sampled. A measure of the correlation between the genealogies of two nucleotides on two sequences is introduced. We show analytically that even when the nucleotides are separated by a large genetic distance, but share MRCA, the genealogies will show only little correlation. This is surprising, because the time until the two nucleotides shared MRCA is reciprocal to the genetic distance. Using simulations, the mean time until all positions in the sample have found a MRCA increases logarithmically with increasing sequence length and is considerably lower than a theoretically predicted upper bound. On the basis of simulations, it turns out that important properties of the coalescent with recombinations of the whole population are reflected in the properties of a sample of low size.

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Genome Sequence Analysis of First Ross River Virus Isolate from Papua New Guinea Indicates Long-Term, Local Evolution

Viruses ◽

10.3390/v13030482 ◽

2021 ◽

Vol 13 (3) ◽

pp. 482

Author(s):

Alice Michie ◽

John S. Mackenzie ◽

David W. Smith ◽

Allison Imrie

Keyword(s):

Papua New Guinea ◽

Large Scale ◽

Solomon Islands ◽

Febrile Illness ◽

New Guinea ◽

Recent Common Ancestor ◽

Ross River Virus ◽

Most Recent Common Ancestor ◽

Mean Time

Ross River virus (RRV) is the most medically significant mosquito-borne virus of Australia, in terms of human morbidity. RRV cases, characterised by febrile illness and potentially persistent arthralgia, have been reported from all Australian states and territories. RRV was the cause of a large-scale epidemic of multiple Pacific Island countries and territories (PICTs) from 1979 to 1980, involving at least 50,000 cases. Historical evidence of RRV seropositivity beyond Australia, in populations of Papua New Guinea (PNG), Indonesia and the Solomon Islands, has been documented. We describe the genomic characterisation and timescale analysis of the first isolate of RRV to be sampled from PNG to date. Our analysis indicates that RRV has evolved locally within PNG, independent of Australian lineages, over an approximate 40 year period. The mean time to most recent common ancestor (tMRCA) of the unique PNG clade coincides with the initiation of the PICTs epidemic in mid-1979. This may indicate that an ancestral variant of the PNG clade was seeded into the region during the epidemic, a period of high RRV transmission. Further epidemiological and molecular-based surveillance is required in PNG to better understand the molecular epidemiology of RRV in the general Australasian region.

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Desiccation-tolerance specific gene expression in leaf tissue of the resurrection plant Sporobolus stapfianus

Functional Plant Biology ◽

10.1071/fp06231 ◽

2007 ◽

Vol 34 (7) ◽

pp. 589 ◽

Cited By ~ 20

Author(s):

Tuan Ngoc Le ◽

Cecilia K. Blomstedt ◽

Jianbo Kuang ◽

Jennifer Tenlen ◽

Donald F. Gaff ◽

...

Keyword(s):

Drought Stress ◽

Desiccation Tolerance ◽

Molecular Mechanisms ◽

Leaf Tissue ◽

Resurrection Plant ◽

Specific Gene ◽

Irreversible Damage ◽

Cellular Processes ◽

Sporobolus Stapfianus ◽

Normal Metabolism

The desiccation tolerant grass Sporobolus stapfianus Gandoger can modulate cellular processes to prevent the imposition of irreversible damage to cellular components by water deficit. The cellular processes conferring this ability are rapidly attenuated by increased water availability. This resurrection plant can quickly restore normal metabolism. Even after loss of more than 95% of its total water content, full rehydration and growth resumption can occur within 24 h. To study the molecular mechanisms of desiccation tolerance in S. stapfianus, a cDNA library constructed from dehydration-stressed leaf tissue, was differentially screened in a manner designed to identify genes with an adaptive role in desiccation tolerance. Further characterisation of four of the genes isolated revealed they are strongly up-regulated by severe dehydration stress and only in desiccation-tolerant tissue, with three of these genes not being expressed at detectable levels in hydrated or dehydrating desiccation-sensitive tissue. The nature of the putative proteins encoded by these genes are suggestive of molecular processes associated with protecting the plant against damage caused by desiccation and include a novel LEA-like protein, and a pore-like protein that may play an important role in peroxisome function during drought stress. A third gene product has similarity to a nuclear-localised protein implicated in chromatin remodelling. In addition, a UDPglucose glucosyltransferase gene has been identified that may play a role in controlling the bioactivity of plant hormones or secondary metabolites during drought stress.

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