Genomic signatures of selection,local adaptation and production type characterisation of East Adriatic sheep breeds

Background The importance of sheep breeding in the Mediterranean part of the eastern Adriatic has a long tradition since its arrival during the Neolithic migrations.Sheep production system is extensive and generally carried out in traditional systems without intensive systematic breeding programmes for high uniform trait production(carcass,wool and milk yield).Therefore,eight indigenous Croatian sheep breeds from eastern Adriatic treated here as metapopulation(EAS),are generally considered as multipurpose breeds(milk,meat and wool),not specialised for a particular type of production,but known for their robustness and resistance to certain environmental conditions.Our objective was to identify genomic regions and genes that exhibit patterns of positive selection signatures,decipher their biological and productive functionality,and provide a"genomic"characterization of EAS adaptation and determine its production type.Results We identified positive selection signatures in EAS using several methods based on reduced local variation,linkage disequilibrium and site frequency spectrum(eROHi,iHS,nSL and CLR).Our analyses identified numerous genomic regions and genes(e.g.,desmosomal cadherin and desmoglein gene families)associated with environmental adaptation and economically important traits.Most candidate genes were related to meat/production and health/immune response traits,while some of the candidate genes discovered were important for domestication and evolutionary processes(e.g.,HOXa gene family and FSIP2).These results were also confirmed by GO and QTL enrichment analysis.Conclusions Our results contribute to a better understanding of the unique adaptive genetic architecture of EAS and define its productive type,ultimately providing a new opportunity for future breeding programmes.At the same time,the numerous genes identified will improve our understanding of ruminant(sheep)robustness and resistance in the harsh and specific Mediterranean environment.

Genetic assessment of inbred chicken lines indicates genomic signatures of resistance to Marek's disease

Background: Marek’s disease(MD) is a highly contagious pathogenic and oncogenic disease primarily affecting chickens. However, the mechanisms of genetic resistance for MD are complex and not fully understood. MD-resistant line 63and MD-susceptible line 72are two highly inbred progenitor lines of White Leghorn. Recombinant Congenic Strains(RCS) were developed from these two lines, which show varied susceptibility to MD.Results: We investigated genetic structure and genomic signatures across the genome, including the line 63and line72, six RCSs, and two reciprocally crossed flocks between the lines 63and 72(F1 63× 72and F1 72× 63) using Affymetrix~? Axiom~? HD 600 K genotyping array. We observed 18 chickens from RCS lines were specifically clustered into resistance sub-groups distributed around line 63. Additionally, homozygosity analysis was employed to explore potential genetic components related to MD resistance, while runs of homozygosity(ROH) are regions of the genome where the identical haplotypes are inherited from each parent. We found several genes including SIK, SOX1, LIG4, SIK1 and TNFSF13B were contained in ROH region identified in resistant group(line 63and RCS), and these genes have been reported that are contribute to immunology and survival. Based on FSTbased population differential analysis, we also identified important genes related to cell death and anti-apoptosis, including AKT1, API5, CDH13, CFDP and USP15,which could be involved in divergent selection during inbreeding process.Conclusions: Our findings offer valuable insights for understanding the genetic mechanism of resistance to MD and the identified genes could be considered as candidate biomarkers in further evaluation.

Genomic Signature for the Prognosis of Survival in Relation to the Tumor Microenvironment in Esophageal Adenocarcinoma

Objective:To establish a new genomic signature for the prognosis of survival in relation to the tumor microenvironment in esophageal adenocarcinoma.Methods:Data from The Cancer Genome Atlas(TCGA)were applied,and the stromal and immune scores of patients with esophageal adenocarcinoma(EAC)were generated through the ESTIMATE algorithm.Differentially expressed genes were obtained,and genes concerning immune prognosis were identified on the basis of these scores.Functional analysis showed that these genes were primarily involved in immunobiological processes.Additionally,CIBERSORT was used to analyze 22 subgroups of tumor-infiltrating immune cells in the tumor microenvironment.Results:The results of the genomic assessment shown on the Kaplan-Meier curve revealed that EAC patients with high-risk scores have the worst survival.The risk score is valid as an independent prognostic factor for the overall survival in EAC patients.The tumor microenvironment was systematically analyzed,and the immune-related prognostic biomarkers of EAC have been proposed.Conclusion:The expression of tumor-infiltrating immune cells and immune-related genes in EAC have been identified.Some previously overlooked genes may be used as additional biomarkers for EAC in the future.

Genomic and phenotypic signatures provide insights into the wide adaptation of a global plant invader

Invasive alien species are primary drivers of biodiversity loss and species extinction.Smooth cordgrass(Spartina alterniflora)is one of the most aggressive invasive plants in coastal ecosystems around the world.However,the genomic bases and evolutionary mechanisms underlying its invasion success have remained largely unknown.Here,we assembled a chromosome-level reference genome and performed phenotypic and population genomic analyses between native US and introduced Chinese populations.Our phenotypic comparisons showed that introduced Chinese populations have evolved competitive traits,such as earlyflowering time and greater plant biomass,during secondary introductions along China’s coast.Population genomic and transcriptomic inferences revealed distinct evolutionary trajectories of low-and high-latitude Chinese populations.In particular,genetic mixture among different source populations,together with in-dependent natural selection acting on distinct target genes,may have resulted in high genome dynamics of the introduced Chinese populations.Our study provides novel phenotypic and genomic evidence showing how smooth cordgrass rapidly adapts to variable environmental conditions in its introduced ranges.Moreover,candidate genes related toflowering time,fast growth,and stress tolerance(i.e.,salinity and submergence)provide valuable genetic resources for future improvement of cereal crops.

Genomic mutation signatures in primary breast cancer and their axillary metastatic lymph nodes

Breast cancer is one of the most common malignant tumors in women all over the world.Metastasis represents a major adverse progression of breast cancer,resulting in poor survival duration.Axillary lymph node metastasis is often the first step of systemic metastasis process of breast cancer.However,themechanismof lymph node metastasis and the genomic signatures of primary breast tumors and lymph node metastasis are still under exploration.Whole exome sequencing was applied to primary breast cancer,axillary metastatic lymph nodes,andwhite blood cells from10Chinesewomen patients in our study.Single nucleotide variants(SNVs)and copynumber variants(CNVs)were compared between primary tumors and lymph nodes for individual patients.There are somatic SNVs(average 5.58±2.56 per megabase)in primary breast cancers and somatic SNVs(average 5.46±2.66 per megabase)in axillary metastatic lymph nodes were identified,which is corresponding to a semblable mutation burden in two malignant sites(P=0.81).No difference was found in CNVs(P=0.33).In primary breast cancer,somatic SNVs(48.12±13.80%)and CNVs(61.72±35.00%)were overlapping with somatic SNVs(49.43±12.30%)and CNVs(72.01±24.31%)in axillary metastatic lymph nodes.Nine genes were screened for significant specificmutations in primary tumors,and 15 genes were significantly mutated in metastatic lymph nodes.Using MutSigCV screening,it was found that HRNR and AHNAK2 are lymph node metastasis-specific genes.In our study,primary breast tumors are directly related to axillary lymph node metastases together and there are most SNVs and CNVs which were overlapping in primary andmetastatic sites.These variants which are overlapping is closely related to themetastatic process of tumor invasion with early genetic variability.This is the first timeto prove the concept of polyclonalmetastaticmodel and in thismodelmore than one clonemigrates establish the metastases to axillary lymph nodes.This study was approved by the institutional review board(IRB)of the Cancer Hospital,Chinese Academy of Medical Sciences,and Peking Union Medical College,China(approval No.NCC2016G-030)on March 3,2016.

Carcinogens that induce the A：T 〉 T：A nucleotide substitutions in the genome

Recently, Ng et al. reported that the A：T 〉 T：A substitutions, proposed to be a signature of aristolochic acid （AA） exposure, were detected in 76/98 （78%） of patients with hepatocellular carcinoma （HCC） from the Taiwan Province of China, and 47% to 1.7% of HCCs from the Chinese mainland and other countries harbored the nucleotide changes. However, other carcinogens, e.g., tobacco carcinogens 4-aminobiphenyl and 1,3-butadiene, air toxic vinyl chloride and its reactive metabolites chloroethylene oxide, melphalan and chlorambucil, also cause this signature in the genome. Since tobacco smoke is a worldwide public health threat and vinyl chloride distributes globally and is an air pollutant in Taiwan Province, the estimation of the patients＇ exposure history is the key to determine the ＂culprit＂ of the A：T 〉 T：A mutations. Apparently, without estimation of the patients＇ exposure history, the conclusion of Ng et al, is unpersuasive and misleading.

Evolution and Variation of the SARS-CoV Genome

Knowledge of the evolution of pathogens is of great medical and biological significance to the prevention, diagnosis, and therapy of infectious diseases. In order to understand the origin and evolution of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus), we collected complete genome sequences of all viruses available in GenBank, and made comparative analyses with the SARS-CoV. Genomic signature analysis demonstrates that the coronaviruses all take the TGTT as their richest tetranucleotide except the SARS-CoV. A detailed analysis of the forty-two complete SARS-CoV genome sequences revealed the existence of two distinct genotypes, and showed that these isolates could be classified into four groups. Our manual analysis of the BLASTN results demonstrates that the HE (hemagglutinin-esterase) gene exists in the SARS-CoV, and many mutations made it unfamiliar to us.