Spain has been one of the main global pandemic epicenters for coronavirus disease 2019(COVID-19).Here,we analyzed>41000 genomes(including>26000 high-quality(HQ)genomes)downloaded from the GISAID repository,inclu...Spain has been one of the main global pandemic epicenters for coronavirus disease 2019(COVID-19).Here,we analyzed>41000 genomes(including>26000 high-quality(HQ)genomes)downloaded from the GISAID repository,including 1245(922 HQ)sampled in Spain.The aim of this study was to investigate genome variation of novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and reconstruct phylogeographic and transmission patterns in Spain.Phylogeographic analysis suggested at least 34 independent introductions of SARS-CoV-2 to Spain at the beginning of the outbreak.Six lineages spread very successfully in the country,probably favored by super-spreaders,namely,A2 a4(7.8%),A2 a5(38.4%),A2 a10(2.8%),B3 a(30.1%),and B9(8.7%),which accounted for 87.9% of all genomes in the Spanish database.One distinct feature of the Spanish SARS-Cov-2 genomes was the higher frequency of B lineages(39.3%,mainly B3 a+B9)than found in any other European country.While B3 a,B9,(and an important sub-lineage of A2 a5,namely,A2 a5 c)most likely originated in Spain,the other three haplogroups were imported from other European locations.The B3 a strain may have originated in the Basque Country from a B3 ancestor of uncertain geographic origin,whereas B9 likely emerged in Madrid.The time of the most recent common ancestor(TMRCA)of SARS-CoV-2 suggested that the first coronavirus entered the country around 11 February 2020,as estimated from the TMRCA of B3 a,the first lineage detected in the country.Moreover,earlier claims that the D614 G mutation is associated to higher transmissibility is not consistent with the very high prevalence of COVID-19 in Spain when compared to other countries with lower disease incidence but much higher frequency of this mutation(56.4% in Spain vs.82.4% in rest of Europe).Instead,the data support a major role of genetic drift in modeling the micro-geographic stratification of virus strains across the country as well as the role of SARS-CoV-2 super-spreaders.展开更多
DEAR EDITOR,Analysis of SARS-CoV-2 genome variation using a minimal number of selected informative sites conforming a genetic barcode presents several drawbacks.We show that purely mathematical procedures for site sel...DEAR EDITOR,Analysis of SARS-CoV-2 genome variation using a minimal number of selected informative sites conforming a genetic barcode presents several drawbacks.We show that purely mathematical procedures for site selection should be supervised by known phylogeny(i)to ensure that solid tree branches are represented instead of mutational hotspots with poor phylogeographic proprieties,and(ii)to avoid phylogenetic redundancy.We propose a procedure that prevents information redundancy in site selection by considering the cumulative informativeness of previously selected sites(as a proxy for phylogenetic-based criteria).This procedure demonstrates that,for short barcodes(e.g.,11 sites),there are thousands of informative site combinations that improve previous proposals.We also show that barcodes based on worldwide databases inevitably prioritize variants located at the basal nodes of the phylogeny,such that most representative genomes in these ancestral nodes are no longer in circulation.Consequently,coronavirus phylodynamics cannot be properly captured by universal genomic barcodes because most SARS-CoV-2 variation is generated in geographically restricted areas by the continuous introduction of domestic variants.展开更多
Pneumonia is an inflammatory condition of the lung with symptoms that include productive dry cough,fever,chest pain,and difficulty breathing,and it is usually caused by viruses and bacteria,but also other microorganis...Pneumonia is an inflammatory condition of the lung with symptoms that include productive dry cough,fever,chest pain,and difficulty breathing,and it is usually caused by viruses and bacteria,but also other microorganisms(such as fungi and parasites).Community-acquired pneumonia(CAP)is a major cause of infectious diseases,hospitalization,and mortality,especially in the elderly population.展开更多
Progressive osseous heteroplasia(POH)is an ultra-rare autosomal dominant disabling disorder characterized by heterotopic ossification(HO).It is caused by heterozygous inactivating mutations in the GNAS(guanine nucleot...Progressive osseous heteroplasia(POH)is an ultra-rare autosomal dominant disabling disorder characterized by heterotopic ossification(HO).It is caused by heterozygous inactivating mutations in the GNAS(guanine nucleotide-binding protein alpha-stimulating activity polypeptide)gene.However,the molecular mechanisms underlying HO remain poorly understood.As a treatment for POH is not yet available,the identification of the mechanisms driving POH in affected tissues using gene expression may be of great help to underestand the molecular basis of POH and develop new therapeutic approaches.展开更多
A frozen mummy was found in Cerro Aconcagua (Argentina)in 1985(Fig.1a-c).Archaeologists identified this mummy as a seven-year-old Inca sacrifice victim living at the time of the Inca Civilization about 500years ago [1...A frozen mummy was found in Cerro Aconcagua (Argentina)in 1985(Fig.1a-c).Archaeologists identified this mummy as a seven-year-old Inca sacrifice victim living at the time of the Inca Civilization about 500years ago [1].The child was sacrificed following an Incan ritual known as capacocha.The complete mitochondrial DNA (mtDNA) genome of this mummy was recently analyzed in Gomez-Carballa et al.[2].This mitogenome belongs to a new sub-branch of the Native American phylogeny named C1bi dated to approximately 14 thousand years ago (loja).Information retrieved from a large database of mtDNA profiles indicated the existence of a few closely related haplotypes in Peru (including one haplotype retrieved from ancient DNA of an individual belonging to the Wari Empire)and the Aymaras from Bolivia.Overall these data suggested a Peruvian Inca origin for this C1bi haplotype,in good agreement with archaeological reports [1].展开更多
Research on biogeographical ancestry(BGA)is becoming of growing interest in forensic genetics and in the biomedical literature(1)Thus,for instance,the need to predict ethnicity of an unknown suspect based on DNA profi...Research on biogeographical ancestry(BGA)is becoming of growing interest in forensic genetics and in the biomedical literature(1)Thus,for instance,the need to predict ethnicity of an unknown suspect based on DNA profiles found at the crime scene is of maximum interest in criminalistics[2],and several autosomal SNP panels have been designed and tested for BGA investigations[3,4].Most of these panels aim at discriminating three main continental groups(sub-Saharan Africans,Europeans,and Asians)by way of testing a number of ancestry informative markers(AIMs)that run from a few dozens to a few hundred[5](see more background in Supplementary data online).展开更多
基金supported by the Instituto de Salud Carlos Ⅲ project Ge PEM(Instituto de Salud Carlos Ⅲ(ISCⅢ)/PI16/01478/Cofinanciado FEDER)DIAVIR(Instituto de Salud Carlos Ⅲ(ISCⅢ)/DTS19/00049/Cofinanciado FEDER+6 种基金Proyecto de Desarrollo Tecnológico en Salud)Resvi-Omics(Instituto de Salud Carlos Ⅲ(ISCⅢ)/PI19/01039/Cofinanciado FEDER)project BI-BACVIR(PRIS-3Agencia de Conocimiento en Salud(ACIS)—Servicio Gallego de Salud(SERGAS)—Xunta de GaliciaSpain)given to A.S.project Re SVinext(Instituto de Salud Carlos Ⅲ(ISCⅢ)/PI16/01569/Cofinanciado FEDER)Enterogen(Instituto de Salud Carlos Ⅲ(ISCⅢ)/PI19/01090/Cofinanciado FEDER)given to F.M.-T。
文摘Spain has been one of the main global pandemic epicenters for coronavirus disease 2019(COVID-19).Here,we analyzed>41000 genomes(including>26000 high-quality(HQ)genomes)downloaded from the GISAID repository,including 1245(922 HQ)sampled in Spain.The aim of this study was to investigate genome variation of novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and reconstruct phylogeographic and transmission patterns in Spain.Phylogeographic analysis suggested at least 34 independent introductions of SARS-CoV-2 to Spain at the beginning of the outbreak.Six lineages spread very successfully in the country,probably favored by super-spreaders,namely,A2 a4(7.8%),A2 a5(38.4%),A2 a10(2.8%),B3 a(30.1%),and B9(8.7%),which accounted for 87.9% of all genomes in the Spanish database.One distinct feature of the Spanish SARS-Cov-2 genomes was the higher frequency of B lineages(39.3%,mainly B3 a+B9)than found in any other European country.While B3 a,B9,(and an important sub-lineage of A2 a5,namely,A2 a5 c)most likely originated in Spain,the other three haplogroups were imported from other European locations.The B3 a strain may have originated in the Basque Country from a B3 ancestor of uncertain geographic origin,whereas B9 likely emerged in Madrid.The time of the most recent common ancestor(TMRCA)of SARS-CoV-2 suggested that the first coronavirus entered the country around 11 February 2020,as estimated from the TMRCA of B3 a,the first lineage detected in the country.Moreover,earlier claims that the D614 G mutation is associated to higher transmissibility is not consistent with the very high prevalence of COVID-19 in Spain when compared to other countries with lower disease incidence but much higher frequency of this mutation(56.4% in Spain vs.82.4% in rest of Europe).Instead,the data support a major role of genetic drift in modeling the micro-geographic stratification of virus strains across the country as well as the role of SARS-CoV-2 super-spreaders.
基金This study was supported by the GePEM(Instituto de Salud Carlos III(ISCIII)/PI16/01478/Cofinanciado FEDER)DIAVIR(Instituto de Salud Carlos III(ISCIII)/DTS19/00049/Cofinanciado FEDER+7 种基金Proyecto de Desarrollo Tecnológico en Salud),Resvi-Omics(Instituto de Salud Carlos III(ISCIII)/PI19/01039/Cofinanciado FEDER),BI-BACVIR(PRIS-3Agencia de Conocimiento en Salud(ACIS)-Servicio Gallego de Salud(SERGAS)-Xunta de GaliciaSpain),Programa Traslaciona Covid-19(ACIS-Servicio Gallego de Salud(SERGAS)-Xunta de GaliciaSpain)and Axencia Galega de Innovación(GAININ607B 2020/08-Xunta de GaliciaSpain)to A.S.and ReSVinext(Instituto de Salud Carlos III(ISCIII)/PI16/01569/Cofinanciado FEDER),and Enterogen(Instituto de Salud Carlos III(ISCIII)/PI19/01090/Cofinanciado FEDER)to F.M.-TWe gratefully acknowledge GISAID and contributing laboratories(Supplementary Table S1)for giving us access to the SAR-CoV-2 genomes used in the present study.
文摘DEAR EDITOR,Analysis of SARS-CoV-2 genome variation using a minimal number of selected informative sites conforming a genetic barcode presents several drawbacks.We show that purely mathematical procedures for site selection should be supervised by known phylogeny(i)to ensure that solid tree branches are represented instead of mutational hotspots with poor phylogeographic proprieties,and(ii)to avoid phylogenetic redundancy.We propose a procedure that prevents information redundancy in site selection by considering the cumulative informativeness of previously selected sites(as a proxy for phylogenetic-based criteria).This procedure demonstrates that,for short barcodes(e.g.,11 sites),there are thousands of informative site combinations that improve previous proposals.We also show that barcodes based on worldwide databases inevitably prioritize variants located at the basal nodes of the phylogeny,such that most representative genomes in these ancestral nodes are no longer in circulation.Consequently,coronavirus phylodynamics cannot be properly captured by universal genomic barcodes because most SARS-CoV-2 variation is generated in geographically restricted areas by the continuous introduction of domestic variants.
基金sponsored by Pfizer.It also received support from Instituto de Salud Carlos III ([ISCIII]TRINEO:No.PI22/00162,DIAVIR:No.DTS19/00049,Resvi-Omics:No.Pl19/01039 (to A.S.)Res Vinext:No.Pl16/01569+7 种基金Enterogen:No.PI19/01090 (to F.M.-T).cofinanciados FEDER,GAIN:Grupos con Potential de Crecimiento No.IN607B 2020/08Grupos de Referencia Competitiva No.IN607A 2023/02 (to A.S.)ACIS:BI-BACVIR No.PRIS-3 (to A.S.),Covid Phy No.SA 304C (to A.S.)consorcio Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias No.CB21/06/00103 (to F.M.-T.)GEN-COVID No.IN845D2020/23 (to F.M.-T.)Grupos de Referencia Competitiva No.IIN607A2021/05 (to F.M.-T).
文摘Pneumonia is an inflammatory condition of the lung with symptoms that include productive dry cough,fever,chest pain,and difficulty breathing,and it is usually caused by viruses and bacteria,but also other microorganisms(such as fungi and parasites).Community-acquired pneumonia(CAP)is a major cause of infectious diseases,hospitalization,and mortality,especially in the elderly population.
文摘Progressive osseous heteroplasia(POH)is an ultra-rare autosomal dominant disabling disorder characterized by heterotopic ossification(HO).It is caused by heterozygous inactivating mutations in the GNAS(guanine nucleotide-binding protein alpha-stimulating activity polypeptide)gene.However,the molecular mechanisms underlying HO remain poorly understood.As a treatment for POH is not yet available,the identification of the mechanisms driving POH in affected tissues using gene expression may be of great help to underestand the molecular basis of POH and develop new therapeutic approaches.
文摘A frozen mummy was found in Cerro Aconcagua (Argentina)in 1985(Fig.1a-c).Archaeologists identified this mummy as a seven-year-old Inca sacrifice victim living at the time of the Inca Civilization about 500years ago [1].The child was sacrificed following an Incan ritual known as capacocha.The complete mitochondrial DNA (mtDNA) genome of this mummy was recently analyzed in Gomez-Carballa et al.[2].This mitogenome belongs to a new sub-branch of the Native American phylogeny named C1bi dated to approximately 14 thousand years ago (loja).Information retrieved from a large database of mtDNA profiles indicated the existence of a few closely related haplotypes in Peru (including one haplotype retrieved from ancient DNA of an individual belonging to the Wari Empire)and the Aymaras from Bolivia.Overall these data suggested a Peruvian Inca origin for this C1bi haplotype,in good agreement with archaeological reports [1].
基金support from the project Ge PEM ISCIII/PI16/01478/Cofinanciado FEDER of the Instituto de Salud Carlos IIIsupport from project Re SVinext ISCIII/PI16/01569/Cofinanciado FEDER
文摘Research on biogeographical ancestry(BGA)is becoming of growing interest in forensic genetics and in the biomedical literature(1)Thus,for instance,the need to predict ethnicity of an unknown suspect based on DNA profiles found at the crime scene is of maximum interest in criminalistics[2],and several autosomal SNP panels have been designed and tested for BGA investigations[3,4].Most of these panels aim at discriminating three main continental groups(sub-Saharan Africans,Europeans,and Asians)by way of testing a number of ancestry informative markers(AIMs)that run from a few dozens to a few hundred[5](see more background in Supplementary data online).
