Deep phylogeny of cancer drivers and compensatory mutations

Rochman, Nash D.; Wolf, Yuri I.; Koonin, Eugene V.

doi:10.1038/s42003-020-01276-7

Cited by 23 publications

(14 citation statements)

References 75 publications

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“…3 D and SI Appendix , Table S3 ; see Brief Methods ), in which the central hubs are D614G in the spike (S) protein and two adjacent substitutions in the nucleocapsid (N) protein, R203K and G204R, the three most common positively selected mutations ( Figs. 1 B and 3 D ) ( 35 ).…”

Section: Resultsmentioning

confidence: 99%

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Ongoing global and regional adaptive evolution of SARS-CoV-2

Rochman

Wolf

Faure

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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209

154

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Understanding the trends in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution is paramount to control the COVID-19 pandemic. We analyzed more than 300,000 high-quality genome sequences of SARS-CoV-2 variants available as of January 2021. The results show that the ongoing evolution of SARS-CoV-2 during the pandemic is characterized primarily by purifying selection, but a small set of sites appear to evolve under positive selection. The receptor-binding domain of the spike protein and the region of the nucleocapsid protein associated with nuclear localization signals (NLS) are enriched with positively selected amino acid replacements. These replacements form a strongly connected network of apparent epistatic interactions and are signatures of major partitions in the SARS-CoV-2 phylogeny. Virus diversity within each geographic region has been steadily growing for the entirety of the pandemic, but analysis of the phylogenetic distances between pairs of regions reveals four distinct periods based on global partitioning of the tree and the emergence of key mutations. The initial period of rapid diversification into region-specific phylogenies that ended in February 2020 was followed by a major extinction event and global homogenization concomitant with the spread of D614G in the spike protein, ending in March 2020. The NLS-associated variants across multiple partitions rose to global prominence in March to July, during a period of stasis in terms of interregional diversity. Finally, beginning in July 2020, multiple mutations, some of which have since been demonstrated to enable antibody evasion, began to emerge associated with ongoing regional diversification, which might be indicative of speciation.

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Section: Resultsmentioning

confidence: 99%

“…Ancestral states were estimated using Fitch Traceback ( 16 ). Statistical associations between mutations were computed largely as previously described ( 35 ) Fig. 3 D and E ( SI Appendix , Table S3 and Fig.…”

Section: Brief Methodsmentioning

confidence: 99%

Ongoing global and regional adaptive evolution of SARS-CoV-2

Rochman

Wolf

Faure

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

209

154

View full text Add to dashboard Cite

show abstract

“…1D and Table S3, see Methods), in which the central hubs are D614G in the spike (S) protein and two adjacent substitutions in the nucleocapsid (N) protein, R203K and G204R, the three most common positively selected mutations (Fig. 1C) (35). Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Statistical associations between mutations were computed in a manner similar to that previously described (24) . Briefly, sequences were leaf-weighted based on the branch lengths of the ultrameterized, tree.…”

Section: Methodsmentioning

confidence: 99%

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Ongoing Global and Regional Adaptive Evolution of SARS-CoV-2

Rochman

Wolf

Faure

et al. 2020

Preprint

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106

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Unprecedented sequencing efforts have, as of October 2020, produced over 100,000 genomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is responsible for the ongoing COVID-19 crisis. Understanding the trends in SARS-CoV-2 evolution is paramount to control the pandemic. Although this extensive data availability quickly facilitated the development of vaccine candidates1, major challenges in the analysis of this enormous dataset persist, limiting the ability of public health officials to translate science into policy. Having evolved over a short period of time, the SARS-CoV-2 isolates show low diversity, necessitating analysis of trees built from genome-scale data. Here we provide a complete ancestral genome reconstruction for SARS-CoV-2 leveraging Fitch Traceback2. We show that the ongoing evolution of SARS-CoV-2 over the course of the pandemic is characterized primarily by purifying selection. However, a small set of sites, including the extensively studied spike 6143, harbor mutations which recurred on multiple, independent occasions, indicative of positive selection. These mutations form a strongly connected network of apparent epistatic interactions. The phylogenetic tree of SARS-CoV-2 consists of 7 major clades which show distinct global and temporal dynamics. Periods of regional diversification of SARS-CoV-2 are short and, despite dramatically reduced travel4, globalization of the virus is apparent.

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