Project description:Koala Retrovirus-A is spreading through wild koalas in a north to south wave while transducing the germline, generating heritable genetic modifications as it transitions to an endogenous retrovirus. In animals south of Brisbane, we previously found that KoRV-A is expressed in the germline, but the resulting unspliced genomic transcripts are processed into sense strand piRNAs, post-transcriptionally suppressing replication. Here we show that this initial “innate” response is prevalent in animals south of the Brisbane River, but KoRV-A promoters are methylated and the virus is transcriptionally silenced in a subpopulation of animals north of the river. Transcriptional silencing correlates with capture of an anti-sense KoRV-A provirus by the 3’UTR of the MAP4K4 gene. The resulting hybrid transcripts are processed into anti-sense piRNAs, which transcriptionally silence established endogenous retroviruses in the germline. This provirus is sweeping through northern koalas, supporting a direct role in adaptive evolution of KoRV-A transcriptional silencing.
Project description:Background Compelling evidence indicates that Shigella species, the etiologic agents of bacillary dysentery, as well as enteroinvasive Escherichia coli, are derived from multiple origins of Escherichia coli and form a single pathovar. To further understand the genome diversity and virulence evolution of Shigella, comparative genomic hybridization microarray analysis was employed to compare the gene content of E. coli K-12 with those of 43 Shigella strains from all serotypes. Results For the 43 strains subjected to CGH microarray analyses, the common backbone of the Shigella genome was estimated to contain more than 1,900 open reading frames, with a mean number of 729 undetectable ORFs. The mosaic distribution of absent regions indicated that insertions and/or deletions have led to the highly diversified genomes of pathogenic strains. Conclusion These results support the hypothesis that by gain and loss of functions, Shigella species became successful human pathogens through convergent evolution from diverse genomic backgrounds. Moreover, we also found many specific differences between different lineages, providing a window into understanding bacterial speciation and taxonomic relationships. Keywords: comparative genomic hybridization
Project description:Koala Retrovirus-A is spreading through wild koalas in a north to south wave while transducing the germline, generating heritable genetic modifications as it transitions to an endogenous retrovirus. In animals south of Brisbane, we previously found that KoRV-A is expressed in the germline, but the resulting unspliced genomic transcripts are processed into sense strand piRNAs, post-transcriptionally suppressing replication. Here we show that this initial “innate” response is prevalent in animals south of the Brisbane River, but KoRV-A promoters are methylated and the virus is transcriptionally silenced in a subpopulation of animals north of the river. Transcriptional silencing correlates with capture of an anti-sense KoRV-A provirus by the 3’UTR of the MAP4K4 gene. The resulting hybrid transcripts are processed into anti-sense piRNAs, which transcriptionally silence established endogenous retroviruses in the germline. This provirus is sweeping through northern koalas, supporting a direct role in adaptive evolution of KoRV-A transcriptional silencing.
Project description:Koala Retrovirus-A is spreading through wild koalas in a north to south wave while transducing the germline, generating heritable genetic modifications as it transitions to an endogenous retrovirus. In animals south of Brisbane, we previously found that KoRV-A is expressed in the germline, but the resulting unspliced genomic transcripts are processed into sense strand piRNAs, post-transcriptionally suppressing replication. Here we show that this initial “innate” response is prevalent in animals south of the Brisbane River, but KoRV-A promoters are methylated and the virus is transcriptionally silenced in a subpopulation of animals north of the river. Transcriptional silencing correlates with capture of an anti-sense KoRV-A provirus by the 3’UTR of the MAP4K4 gene. The resulting hybrid transcripts are processed into anti-sense piRNAs, which transcriptionally silence established endogenous retroviruses in the germline. This provirus is sweeping through northern koalas, supporting a direct role in adaptive evolution of KoRV-A transcriptional silencing.
Project description:Esophageal squamous cell carcinoma (ESCC) is an aggressive cancer with one of the highest world incidences in the Eastern Cape region of South Africa. Several genome wide studies have been performed on ESCC cohorts from Asian countries, North America, Malawi and other parts of the world but none has been conducted on ESCC tumors from South Africa to date, where the molecular pathology and etiology of this disease remains unclear. We report here tumor associated copy number changes observed in 51 ESCC patients’ samples from the Eastern Cape province of South Africa. We extracted tumor DNA from 51 archived ESCC specimens and interrogated tumor associated DNA copy number changes using Affymetrix® 500K SNP array technology. The Genomic Identification of Significant Targets in Cancer (GISTIC) algorithm was applied to identify significant focal regions of gains and losses. Gains of the top recurrent cancer genes were validated by fluorescence in situ hybridization and their protein expression assessed by immunohistochemistry. Twenty-three significant focal gains were identified across samples. Gains involving the CCND1, MYC, EGFR and JAG1 loci recapitulated those described in studies on Asian and Malawian cohorts. The two most significant gains involved the chromosomal sub-bands 3q28, encompassing the TPRG1 gene and 11q13.3 including the CTTN, PPFIA1and SHANK2 genes. There was no significant homozygous loss and the most recurrent hemizygous deletion involved the B3GAT1 gene on chromosome11q25. Focal gains on 11q13.3 in 37% of cases (19/51), consistently involved CTTN and SHANK2 genes. Twelve of these cases (23,5%), had a broader region of gain that also included the CCND1, FGF19, FGF4 and FGF3 genes. SHANK2 and CTTN are co-amplified in several cancers, these proteins interact functionally together and are involved in cell motility. Immunohistochemistry confirmed both Shank2 (79%) and cortactin (69%) protein overexpression in samples with gains of these genes. In contrast, cyclin D1 (65%) was moderately expressed in samples with CCND1 DNA gain. This study reports copy number changes in a South African ESCC cohort and highlights similarities and differences with cohorts from Asia and Malawi. Our results strongly suggest a role for CTTN and SHANK2 in the pathogenesis of ESCC in South Africa.
Project description:The emergence and fast global spread of COVID-19 has presented one of the greatest public health challenges in modern times with no proven cure or vaccine. Africa is still early in this epidemic, therefore the extent of disease severity is not yet clear. We used a mathematical model to fit to the observed cases of COVID-19 in South Africa to estimate the basic reproductive number and critical vaccination coverage to control the disease for different hypothetical vaccine efficacy scenarios. We also estimated the percentage reduction in effective contacts due to the social distancing measures implemented. Early model estimates show that COVID-19 outbreak in South Africa had a basic reproductive number of 2.95 (95% credible interval [CrI] 2.83–3.33). A vaccine with 70% efficacy had the capacity to contain COVID-19 outbreak but at very higher vaccination coverage 94.44% (95% Crl 92.44–99.92%) with a vaccine of 100% efficacy requiring 66.10% (95% Crl 64.72–69.95%) coverage. Social distancing measures put in place have so far reduced the number of social contacts by 80.31% (95% Crl 79.76–80.85%). These findings suggest that a highly efficacious vaccine would have been required to contain COVID-19 in South Africa. Therefore, the current social distancing measures to reduce contacts will remain key in controlling the infection in the absence of vaccines and other therapeutics.