Deamidation of two asparagines activates a conditional PEST sequence to target Bcl-xL for degradation.
Templeton AR, Mills JC. Evolution of the human gastrokine locus and confounding factors regarding the pseudogenicity of GKN3. Physiol Genomics 45: 667-683, 2013. First published May 28, 2013 doi:10.1152/physiolgenomics.00169.2012.-In a screen for genes expressed specifically in gastric mucous neck cells, we identified GKN3, the recently discovered third member of the gastrokine family. We present confirmatory mouse data and novel porcine data showing that mouse GKN3 expression is confined to mucous cells of the corpus neck and antrum base and is prominently expressed in metaplastic lesions. GKN3 was proposed originally to be expressed in some human populations and a pseudogene in others. To investigate that hypothesis, we studied human GKN3 evolution in the context of its paralogous genomic neighbors, GKN1 and GKN2. Haplotype analysis revealed that GKN3 mimics GKN2 in patterns of exonic SNP allocation, whereas GKN1 appeared to be more stringently selected. GKN3 showed signatures of both directional selection and population based selective sweeps in humans. One such selective sweep includes SNP rs10187256, originally identified as an ancestral tryptophan to premature STOP codon mutation. The derived (nonancestral) allele went to fixation in Asia. We show that another SNP, rs75578132, identified 5 bp downstream of rs10187256, exhibits a second selective sweep in almost all Europeans, some Latinos, and some Africans, possibly resulting from a reintroduction of European genes during African colonization. Finally, we identify a mutation that would destroy the splice donor site in the putative exon3-intron3 boundary, which occurs in all human genomes examined to date. Our results highlight a stomach-specific human genetic locus, which has undergone various selective sweeps across European, Asian, and African populations and thus reflects geographic and ethnic patterns in genome evolution.
The spread of the corona virus around the world has spurred travel restrictions and community lockdowns to manage the transmission of infection. In the Philippines, with a large population of overseas Filipino contract workers (OFWs), as well as foreign workers in the local online gaming industry and visitors from nearby countries, the first reported cases were from a Chinese couple visiting the country in mid-January 2020. Three months on, by mid-March, the COVID-19 cases in the Philippines had reached its first 100, before it exploded to the present 178,022 cases (as of August 20, 2020). Here, we report a genomic survey of six (6) whole genomes of the SARS-CoV-2 virus collected from COVID-19 patients seen at the Philippine General Hospital, the major referral hospital for COVID-19 cases in Metro Manila at about the time the Philippines had over a hundred cases. Analysis of commonly observed variants did not reveal a clear pattern of the virus evolving towards a more infectious and severe strain. When combined with other available viral sequences from the Philippines and from GISAID, phylogenomic analysis reveal that the sequenced Philippine isolates can be classified into three primary groups based on collection dates and possible infection sources: (1) January samples collected in the early phases of the pandemic that are closely associated with isolates from Wuhan, China; (2) March samples that are mainly linked to the M/V Diamond Princess Cruise Ship outbreak; and (3) June samples that clustered with European isolates, one of which already harbor the globally prevalent D614G mutation which initially circulated in Europe. The presence of community-acquired viral transmission amidst compulsory and strict quarantine protocols, particularly for repatriated Filipino workers, highlights the need for a refinement of the quarantine, testing, and tracing strategies currently being implemented to adapt to the current pandemic situation.
We report the sequencing and detection of 39 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) samples containing lineage-defining mutations specific to viruses belonging to the B.1.1.7 lineage (UK variant) in the Philippines.
We report the sequencing and analysis of 60 XBC and 114 XBC.1 SARS-CoV-2 lineages detected in the Philippines from August to September 2022, which are regarded as recombinant lineages of the BA.2 Omicron and B.1.617.2 Delta (21I Clade) variants. The sequences described here place the Philippines as the country with the earliest and highest number of XBC and XBC.1 cases within the included period. Majority of the detected cases were sampled from the adjacent Davao and Soccskargen regions in southern Philippines, but have also been observed at lower proportions in other regions of the country. Time-scaled phylogenetic analysis with global samples from GISAID reaffirms the supposed root of XBC-like cases from the Philippines. Furthermore, the apparent clustering of some foreign cases separate from those collected in the country suggests several occurrences of cross-border transmissions resulting in the spread of XBC-like lineages within and among those countries. The consensus mutation profile shows regions harboring mutations specific to either the Omicron BA.2 or Delta B.1.617.2 lineages, supporting the recombinant nature of XBC. Finally, alternative allele fraction pattern and intrahost mutation analysis revealed that a relatively early case of XBC collected in March 2022 is likely to be an active co-infection event. This suggests that co-infection of Omicron and Delta was already occurring in the Philippines early in 2022, facilitating the generation of recombinants that may have further evolved and gained additional mutations enabling its spread across certain local populations at a later time.
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