Biology subjects

Mcbroome, J.

Publications and source records attributed to Mcbroome, J..

3 recordsLinked to original sources

bioRxiv2021

Pandemic-Scale Phylogenomics Reveals Elevated Recombination Rates in the SARS-CoV-2 Spike Region

Accurate and timely detection of recombinant lineages is crucial for interpreting genetic variation, reconstructing epidemic spread, identifying selection and variants of interest, and accurately performing phylogenetic analyses. During the SARS-CoV-2 pandemic, genomic data generation has exceeded the capacities of existing analysis platforms, thereby crippling real-time analysis of viral recombination. Low SARS-CoV-2 mutation rates make detecting recombination difficult. Here, we develop and apply a novel phylogenomic method to exhaustively search a nearly comprehensive SARS-CoV-2 phylogeny for recombinant lineages. We investigate a 1.6M sample tree, and identify 606 recombination events. Approximately 2.7% of sequenced SARS-CoV-2 genomes have recombinant ancestry. Recombination breakpoints occur disproportionately in the Spike protein region. Our method empowers comprehensive real time tracking of viral recombination during the SARS-CoV-2 pandemic and beyond.

evolutionary biology↗

bioRxiv2021

A new SARS-CoV-2 lineage that shares mutations with known Variants of Concern is rejected by automated sequence repository quality control

We report a SARS-CoV-2 lineage that shares N501Y, P681H, and other mutations with known variants of concern, such as B.1.1.7. This lineage, which we refer to as B.1.x (COG-UK sometimes references similar samples as B.1.324.1), is present in at least 20 states across the USA and in at least six countries. However, a large deletion causes the sequence to be automatically rejected from repositories, suggesting that the frequency of this new lineage is underestimated using public data. Recent dynamics based on 339 samples obtained in Santa Cruz County, CA, USA suggest that B.1.x may be increasing in frequency at a rate similar to that of B.1.1.7 in Southern California. At present the functional differences between this variant B.1.x and other circulating SARS-CoV-2 variants are unknown, and further studies on secondary attack rates, viral loads, immune evasion and/or disease severity are needed to determine if it poses a public health concern. Nonetheless, given what is known from well-studied circulating variants of concern, it seems unlikely that the lineage could pose larger concerns for human health than many already globally distributed lineages. Our work highlights a need for rapid turnaround time from sequence generation to submission and improved sequence quality control that removes submission bias. We identify promising paths toward this goal.

genomics↗

bioRxiv2019

Fine-mapping complex inversion breakpoints and investigating somatic pairing in the Anopheles gambiae species complex using proximity-ligation sequencing

Chromosomal inversions are fundamental drivers of genome evolution. In the main afro-tropical malaria vector species, belonging to the Anopheles gambiae species complex, inversions play an important role in local adaptation and have a rich history of cytological study. Despite the importance and ubiquity of some chromosomal inversions across the species complex, inversion breakpoints are often challenging to map molecularly due to the presence of large repetitive regions. Here, we develop an approach that uses Hi-C sequencing data to molecularly fine-map the breakpoints of inversions 2Rbc and 2Rd in A. coluzzii. We found that inversion breakpoints occur in large repetitive regions, and strikingly among three inversions analyzed, two breakpoints appear to be reused in two separate inversions. Additionally, we use heterozygous individuals to quantitatively investigate somatic pairing disruption in the regions immediately surrounding inversion breakpoints, and we find that pairing disruption is undetectable beyond approximately 250 Kb from the inversion breakpoints.

evolutionary biology↗