Biology subjects

Nemudraia, A.

Publications and source records attributed to Nemudraia, A..

5 recordsLinked to original sources

bioRxiv2023

The diverse evolutionary histories of domesticated metaviral capsid genes in mammals

Selfish genetic elements and their remnants comprise at least half of the human genome. Active transposons duplicate by inserting copies at new sites in a host genome. Following insertion, transposons can acquire mutations that render them inactive; the accrual of additional mutations can render them unrecognizable over time. However, in rare instances, segments of transposons become useful for the host, in a process called gene domestication. Using the first complete human genome assembly and 25 additional vertebrate genomes, we analyzed the evolutionary trajectories and functional potential of genes domesticated from the capsid genes of Metaviridae, a retroviral-like retrotransposon family. Our analysis reveals four families of domesticated capsid genes in placental mammals with varied evolutionary outcomes, ranging from universal retention to lineage-specific duplications or losses and from purifying selection to lineage-specific rapid evolution. The four families of domesticated capsid genes have divergent amino-terminal domains, inherited from four distinct ancestral metaviruses. Structural predictions reveal that many domesticated genes encode a previously unrecognized RNA-binding domain retained in multiple paralogs in mammalian genomes both adjacent to and independent from the capsid domain. Collectively, our study reveals diverse outcomes of domestication of diverse metaviruses, which led to structurally and evolutionarily diverse genes that encode important, but still largely-unknown functions in placental mammals.

bioinformatics↗

bioRxiv2023

Repair of CRISPR-guided RNA breaks enables site-specific RNA editing in human cells.

Genome editing with CRISPR RNA-guided endonucleases generates DNA breaks that are resolved by cellular DNA repair machinery. However, analogous methods to manipulate RNA remain unavailable. Here, we show that site-specific RNA breaks generated with RNA-targeting CRISPR complexes are repaired in human cells, and this repair can be used for programmable deletions in human transcripts that restore gene function. Collectively, this work establishes a technology for precise RNA manipulation with potential therapeutic applications. One-Sentence SummaryCRISPR-guided RNA breaks are repaired in human cells, and this RNA repair can be used for programmable editing of human transcriptomes.

molecular biology↗

bioRxiv2023

CRISPR-based engineering of RNA viruses

CRISPR RNA-guided endonucleases have enabled precise editing of DNA. However, options for editing RNA remain limited. Here, we combine sequence-specific RNA cleavage by CRISPR ribonucleases with programmable RNA repair to make precise deletions and insertions in RNA. This work establishes a new recombinant RNA technology with immediate applications for the facile engineering of RNA viruses. One-Sentence SummaryProgrammable CRISPR RNA-guided ribonucleases enable recombinant RNA technology.

molecular biology↗

bioRxiv2022

The rise and fall of SARS-CoV-2 variants and the emergence of competing Omicron lineages

In late December of 2019, high throughput sequencing technologies enabled rapid identification of SARS-CoV-2 as the etiological agent of COVID-19, and global sequencing efforts are now a critical tool for monitoring the ongoing spread and evolution of this virus. Here, we analyze a subset (n=83,204) of all publicly available SARS-CoV-2 genomes (n=~5.6 million) that were randomly selected, but equally distributed over the course of the pandemic. We plot the emergence and extinction of new variants of concern (VOCs) over time and show how this corresponds to the ongoing accumulation of mutations in SARS-CoV-2 genomes and individual proteins. While the accumulation of mutations generally follows a linear regression, non-synonymous mutations are significantly greater in Omicron viruses than in previous variants-especially in the spike and nucleoproteins-and these differences are more pronounced in a recently identified sub-lineage (BA.2) of Omicron. ImportanceOmicron is the fifth SARS-CoV-2 variant to be designated a Variant of Concern (VOC) by the World Health Organization (WHO). Here we provide a retrospective analysis of SARS-CoV-2 variants and explain how the Omicron variant is distinct. Our work shows that the spike and nucleoproteins have accumulated the most mutations in Omicron variants, but that the accessory proteins of SARS-CoV-2 sequences are changing most rapidly relative to their size. Collectively, this "Observation" provides a concise overview of SARS-CoV-2 evolution, reveals mutational differences between two Omicron lineages, and highlights changes in the SARS-CoV-2 proteome that have been under reported.

evolutionary biology↗

bioRxiv2021

The rise and fall of SARS-CoV-2 variants and the mutational profile of Omicron

In late December of 2019, high throughput sequencing technologies enabled rapid identification of SARS-CoV-2 as the etiological agent of COVID-19, and global sequencing efforts are now a critical tool for monitoring the ongoing spread and evolution of this virus. Here, we analyze a subset (n=87,032) of all publicly available SARS-CoV-2 genomes (n=[~]5.6 million) that were randomly selected, but equally distributed over the course of the pandemic. We plot the appearance of new variants of concern (VOCs) over time and show that the mutation rates in Omicron viruses are significantly greater than those in previously identified SARS-CoV-2 variants. Mutations in Omicron are primarily restricted to the spike protein, while 25 other viral proteins-- including those involved in SARS-CoV-2 replication--are highly conserved. Collectively, this suggests that the genetic distinction of Omicron primarily arose from selective pressures on the spike, and that the fidelity of replication of this variant has not been altered. ImportanceOmicron is the fifth SARS-CoV-2 variant to be designated a Variant of Concern (VOC) by the World Health Organization (WHO). Here we provide a retrospective analysis of SARS-CoV-2 variants and explain how the Omicron variant is distinct. Our work shows that the spike protein is a hotspot for viral evolution in all variants, suggesting that existing vaccines and diagnostics that target this protein may become less effective against Omicron and that our therapeutic and public health strategies will have to evolve along with the virus.

evolutionary biology↗