Engineering topics

Nasir, Arshan

Publications and source records attributed to Nasir, Arshan.

7 records

DOE OSTI2021

Large Evolutionary Rate Heterogeneity among and within HIV-1 Subtypes and CRFs

HIV-1 is a fast-evolving, genetically diverse virus presently classified into several groups and subtypes. The virus evolves rapidly because of an error-prone polymerase, high rates of recombination, and selection in response to the host immune system and clinical management of the infection. The rate of evolution is also influenced by the rate of virus spread in a population and nature of the outbreak, among other factors. HIV-1 evolution is thus driven by a range of complex genetic, social, and epidemiological factors that complicates disease management and prevention. Here, we quantify the evolutionary (substitution) rate heterogeneity among major HIV-1 subtypes and recombinants by analyzing the largest collection of HIV-1 genetic data spanning the widest possible geographical (100 countries) and temporal (1981–2019) spread. We show that HIV-1 substitution rates vary substantially, sometimes by several folds, both across the virus genome and between major subtypes and recombinants, but also within a subtype. Across subtypes, rates ranged 3.5-fold from 1.34 × 10−3 to 4.72 × 10−3 in env and 2.3-fold from 0.95 × 10−3 to 2.18 × 10−3 substitutions site−1 year−1 in pol. Within the subtype, 3-fold rate variation was observed in env in different human populations. It is possible that HIV-1 lineages in different parts of the world are operating under different selection pressures leading to substantial rate heterogeneity within and between subtypes. We further highlight how such rate heterogeneity can complicate HIV-1 phylodynamic studies, specifically, inferences on epidemiological linkage of transmission clusters based on genetic distance or phylogenetic data, and can mislead estimates about the timing of HIV-1 lineages.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2021

The tree of life describes a tripartite cellular world

The canonical view of a 3-domain (3D) tree of life was recently challenged by the discovery of Asgardarchaeota encoding eukaryote signature proteins (ESPs), which were treated as missing links of a 2-domain (2D) tree. Here we revisit the debate. We discuss methodological limitations of building trees with alignment-dependent approaches, which often fail to satisfactorily address the problem of ‘‘gaps.’’ In addition, most phylogenies are reconstructed unrooted, neglecting the power of direct rooting methods. Alignment-free methodologies lift most difficulties but require employing realistic evolutionary models. We argue that the discoveries of Asgards and ESPs, by themselves, do not rule out the 3D tree, which is strongly supported by comparative and evolutionary genomic analyses and vast genomic and biochemical superkingdom distinctions. Given uncertainties of retrodiction and interpretation difficulties, we conclude that the 3D view has not been falsified but instead has been strengthened by genomic analyses. In turn, the objections to the 2D model have not been lifted. The debate remains open. Also see the video abstract here: https://youtu.be/-6TBN0bubI8

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2020

What Should Health Departments Do with HIV Sequence Data?

Many countries and US states have mandatory statues that require reporting of HIV clinical data including genetic sequencing results to the public health departments. Because genetic sequencing is a part of routine care for HIV infected persons, health departments have extensive sequence collections spanning years and even decades of the HIV epidemic. How should these data be used (or not) in public health practice? This is a complex, multi-faceted question that weighs personal risks against public health benefit. The answer is neither straightforward nor universal. However, to make that judgement—of how genetic sequence data should be used in describing and combating the HIV epidemic—we need a clear image of what a phylogenetically enhanced HIV surveillance system can do and what benefit it might provide. In this paper, we present a positive case for how up-to-date analysis of HIV sequence databases managed by health departments can provide unique and actionable information of how HIV is spreading in local communities. We discuss this question broadly, with examples from the US, as it is globally relevant for all health authorities that collect HIV genetic data.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2020

The origin and evolution of viruses inferred from fold family structure

The canonical frameworks of viral evolution describe viruses as cellular predecessors, reduced forms of cells, or entities that escaped cellular control. The discovery of giant viruses has changed these standard paradigms. Their genetic, proteomic and structural complexities resemble those of cells, prompting a redefinition and reclassification of viruses. In a previous genome-wide analysis of the evolution of structural domains in proteomes, with domains defined at the fold superfamily level, we found the origins of viruses intertwined with those of ancient cells. In this review, we extend these data-driven analyses to the study of fold families confirming the co-evolution of viruses and ancient cells and the genetic ability of viruses to foster molecular innovation. The results support our suggestion that viruses arose by genomic reduction from ancient cells and validate a co-evolutionary ‘symbiogenic’ model of viral origins.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2020

Editorial: Viruses, Genetic Exchange, and the Tree of Life

We live in exciting times for microbiology research. The significant technological and scientific advancements in the past decades have now enabled scientists to pursue discovery and description of novel microbial and viral linages from previously uncharted Earth habitats. Two such discoveries are particularly exciting and noteworthy in this regard. First, the discovery of the first ‘giant virus’, Acanthamoeba polyphaga mimivirus, in 2003, and several others thereafter, posed intriguing questions regarding virus origins, evolution, classification, and their place in the ‘tree of life’. Second, the discoveries of ‘Lokiarchaeota’ and several other closelyrelated archaeal members that encode several eukaryote-specific proteins challenged the threedomain canonical structure of the tree of life. These discoveries have reopened debates on central questions in evolutionary biology research such as the origin of viruses, the origin of eukaryotes, evolutionary relationship between Archaea and Eukarya, and the structure and topology of the tree of life. In this Research Topic, we received a broad range of contributions addressing these and other related questions.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2020

Complete genome of Polaromonas vacuolata KCTC 22033 T isolated from beneath Antarctic Sea ice

Polaromonas vacuolata KCTC 22033 T is an obligate aerobic, Gram-negative, psychrophilic and rod-shaped bacterium isolated from beneath the sea ice off the coast of the Palmer Peninsula, Anvers Islands, Antarctica. P. vacuolata is the type species of Polaromonas genus and the first example of gas vacuolate Betaproteobacteria isolated from marine habitats. In this study, we report a complete genome of P. vacuolata KCTC 22033 T , which consists of 3,837,686 bp (G + C content of 52.07%) with a single chromosome, 3461 protein-coding genes, 56 tRNAs and 6 rRNA operons. Genomic analysis revealed the presence of genes involved in bacterial adaptation under saline conditions, cold adaptation via the production of gas vesicles and cell adhesion proteins, and a photoheterotrophic lifestyle when challenged by starvation. Intriguingly, several of these genes were likely acquired from species outside the Polaromonas genus. The genomic information therefore describes the unique evolution and adaptation of P. vacuolata to its extraordinary habitat, i.e., beneath the Antarctic sea ice.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2020

Bacterial Origin and Reductive Evolution of the CPR Group

The candidate phyla radiation (CPR) is a proposed subdivision within the bacterial domain comprising several candidate phyla. CPR organisms are united by small genome and physical sizes, lack several metabolic enzymes, and populate deep branches within the bacterial subtree of life. Here, these features raise intriguing questions regarding their origin and mode of evolution. In this study, we performed a comparative and phylogenomic analysis to investigate CPR origin and evolution. Unlike previous gene/protein sequence-based reports of CPR evolution, we used protein domain superfamilies classified by protein structure databases to resolve the evolutionary relationships of CPR with non-CPR bacteria, Archaea, Eukarya, and viruses. Across all supergroups, CPR shared maximum superfamilies with non-CPR bacteria and were placed as deep branching bacteria in most phylogenomic trees. CPR contributed 1.22% of new superfamilies to bacteria including the ribosomal protein L19e and encoded four core superfamilies that are likely involved in cell-to-cell interaction and establishing episymbiotic lifestyles. Although CPR and non-CPR bacterial proteomes gained common superfamilies over the course of evolution, CPR and Archaea had more common losses. These losses mostly involved metabolic superfamilies. In fact, phylogenies built from only metabolic protein superfamilies separated CPR and non-CPR bacteria. These findings indicate that CPR are bacterial organisms that have probably evolved in an Archaea-like manner via the early loss of metabolic functions. We also discovered that phylogenies built from metabolic and informational superfamilies gave contrasting views of the groupings among Archaea, Bacteria, and Eukarya, which add to the current debate on the evolutionary relationships among superkingdoms.

59 BASIC BIOLOGICAL SCIENCES↗