Gene-Environment Interactions: My Unique Journey.

I am deeply honored to be invited to write this scientific autobiography. As a physician-scientist, pediatrician, molecular biologist, and geneticist, I have authored/coauthored more than 600 publications in the fields of clinical medicine, biochemistry, biophysics, pharmacology, drug metabolism, toxicology, molecular biology, cancer, standardized gene nomenclature, developmental toxicology and teratogenesis, mouse genetics, human genetics, and evolutionary genomics. Looking back, I think my career can be divided into four distinct research areas, which I summarize mostly chronologically in this article: (a) discovery and characterization of the AHR/CYP1 axis, (b) pharmacogenomics and genetic prediction of response to drugs and other environmental toxicants, (c) standardized drug-metabolizing gene nomenclature based on evolutionary divergence, and (d) discovery and characterization of the SLC39A8 gene encoding the ZIP8 metal cation influx transporter. Collectively, all four topics embrace gene-environment interactions, hence the title of my autobiography.

Ambiviricota, a novel ribovirian phylum for viruses with viroid-like properties.

Fungi harbor a vast diversity of mobile genetic elements (MGEs). Recently, novel fungal MGEs, tentatively referred to as 'ambiviruses,' were described. 'Ambiviruses' have single-stranded RNA genomes of about 4-5 kb in length that contain at least two open reading frames (ORFs) in non-overlapping ambisense orientation. Both ORFs are conserved among all currently known 'ambiviruses,' and one of them encodes a distinct viral RNA-directed RNA polymerase (RdRP), the hallmark gene of ribovirian kingdom Orthornavirae. However, 'ambivirus' genomes are circular and predicted to replicate via a rolling-circle mechanism. Their genomes are also predicted to form rod-like structures and contain ribozymes in various combinations in both sense and antisense orientations-features reminiscent of viroids, virusoids, ribozyvirian kolmiovirids, and yet-unclassified MGEs (such as 'epsilonviruses,' 'zetaviruses,' and some 'obelisks'). As a first step toward the formal classification of 'ambiviruses,' the International Committee on Taxonomy of Viruses (ICTV) recently approved the establishment of a novel ribovirian phylum, Ambiviricota, to accommodate an initial set of 20 members with well-annotated genome sequences.

Promotion of order Bunyavirales to class Bunyaviricetes to accommodate a rapidly increasing number of related polyploviricotine viruses.

Prior to 2017, the family Bunyaviridae included five genera of arthropod and rodent viruses with tri-segmented negative-sense RNA genomes related to the Bunyamwera virus. In 2017, the International Committee on Taxonomy of Viruses (ICTV) promoted the family to order Bunyavirales and subsequently greatly expanded its composition by adding multiple families for non-segmented to polysegmented viruses of animals, fungi, plants, and protists. The continued and accelerated discovery of bunyavirals highlighted that an order would not suffice to depict the evolutionary relationships of these viruses. Thus, in April 2024, the order was promoted to class Bunyaviricetes. This class currently includes two major orders, Elliovirales (Cruliviridae, Fimoviridae, Hantaviridae, Peribunyaviridae, Phasmaviridae, Tospoviridae, and Tulasviridae) and Hareavirales (Arenaviridae, Discoviridae, Konkoviridae, Leishbuviridae, Mypoviridae, Nairoviridae, Phenuiviridae, and Wupedeviridae), for hundreds of viruses, many of which are pathogenic for humans and other animals, plants, and fungi.

Changes in fungal taxonomy: mycological rationale and clinical implications.

Numerous fungal species of medical importance have been recently subjected to and will likely continue to undergo nomenclatural changes as a result of the application of molecular approaches to fungal classification together with abandonment of dual nomenclature. Here, we summarize those changes affecting key groups of fungi of medical importance, explaining the mycological (taxonomic) rationale that underpinned the changes and the clinical relevance/importance (where such exists) of the key nomenclatural revisions. Potential mechanisms to mitigate unnecessary taxonomic instability are suggested, together with approaches to raise awareness of important changes to minimize potential clinical confusion.

"Deoxy" to be or "Desoxy" not to be-a century-old tale in the history of DNA nomenclature.

This commentary discusses a comprehensive history of the first-ever use of pertinent words directly related to DNA, such as desoxyribose, deoxyribose, desoxyribonucleic acid, and deoxyribonucleic acid. With almost 100 years of the identification and nomenclature of desoxyribose sugar and desoxyribonucleic acid, the term "desoxy" continues to see limited use. We hope that whenever young researchers come across the sporadic occurrence of "desoxy" in any published text, they will not consider it a mistake.

Phenotypic and spatial heterogeneity of CD8+ tumour infiltrating lymphocytes.

CD8+ T cells are the workhorses executing adaptive anti-tumour response, and targets of various cancer immunotherapies. Latest advances have unearthed the sheer heterogeneity of CD8+ tumour infiltrating lymphocytes, and made it increasingly clear that the bulk of the endogenous and therapeutically induced tumour-suppressive momentum hinges on a particular selection of CD8+ T cells with advantageous attributes, namely the memory and stem-like exhausted subsets. A scrutiny of the contemporary perception of CD8+ T cells in cancer and the subgroups of interest along with the factors arbitrating their infiltration contextures, presented herein, may serve as the groundwork for future endeavours to probe further into the regulatory networks underlying their differentiation and migration, and optimise T cell-based immunotherapies accordingly.

Proposal for a Global Classification and Nomenclature System for A/H9 Influenza Viruses.

Influenza A/H9 viruses circulate worldwide in wild and domestic avian species, continuing to evolve and posing a zoonotic risk. A substantial increase in human infections with A/H9N2 subtype avian influenza viruses (AIVs) and the emergence of novel reassortants carrying A/H9N2-origin internal genes has occurred in recent years. Different names have been used to describe the circulating and emerging A/H9 lineages. To address this issue, an international group of experts from animal and public health laboratories, endorsed by the WOAH/FAO Network of Expertise on Animal Influenza, has created a practical lineage classification and nomenclature system based on the analysis of 10,638 hemagglutinin sequences from A/H9 AIVs sampled worldwide. This system incorporates phylogenetic relationships and epidemiologic characteristics designed to trace emerging and circulating lineages and clades. To aid in lineage and clade assignment, an online tool has been created. This proposed classification enables rapid comprehension of the global spread and evolution of A/H9 AIVs.

An expert discussion on the atypical hemolytic uremic syndrome nomenclature-identifying a road map to precision: a report of a National Kidney Foundation Working Group.

The term atypical hemolytic uremic syndrome has been in use since the mid-1970s. It was initially used to describe the familial or sporadic form of hemolytic uremic syndrome as opposed to the epidemic, typical form of the disease. Over time, the atypical hemolytic uremic syndrome term has evolved into being used to refer to anything that is not Shiga toxin-associated hemolytic uremic syndrome. The term describes a heterogeneous group of diseases of disparate causes, a circumstance that makes defining disease-specific natural history and/or targeted treatment approaches challenging. A working group of specialty-specific experts in the thrombotic microangiopathies was convened to review the validity of this broad term in an era of swiftly advancing science and targeted therapeutics. A Delphi approach was used to define and interrogate some of the key issues related to the atypical hemolytic uremic syndrome nomenclature.

A guide to naming human non-coding RNA genes.

Research on non-coding RNA (ncRNA) is a rapidly expanding field. Providing an official gene symbol and name to ncRNA genes brings order to otherwise potential chaos as it allows unambiguous communication about each gene. The HUGO Gene Nomenclature Committee (HGNC, www.genenames.org) is the only group with the authority to approve symbols for human genes. The HGNC works with specialist advisors for different classes of ncRNA to ensure that ncRNA nomenclature is accurate and informative, where possible. Here, we review each major class of ncRNA that is currently annotated in the human genome and describe how each class is assigned a standardised nomenclature.

Valid and accepted novel bacterial taxa isolated from non-domestic animals and taxonomic revisions published in 2023.

Continued investigation into the bacteria associated with non-domestic animals provides important information for recognizing normal flora, assessing the health status of these unique species of animals, and identifying new or emerging pathogens of concern. In this summary of novel taxa and taxonomic revisions, considerable additions have been made toward understanding fecal and mucosal flora in multiple wild animal species. In addition, novel pathogenic bacteria are discussed, including multiple Chlamydia spp. causing disease in a hawk and crocodile, two Corynebacterium spp. causing oral lesions in penguins and a lesser-known genus, Mergibacter within Family Pasteurellaceae, causing disease in multiple wild bird species. Finally, a few revisions to bacteria isolated from normal non-domestic animal body sites are mentioned.

Twenty years of big plant genera.

In 2004, David Frodin published a landmark review of the history and concepts of big plant genera. Two decades of taxonomic activity have taken place since, coinciding with a revolution in phylogenetics and taxonomic bioinformatics. Here we use data from the World Flora Online (WFO) to provide an updated list of big (more than 500 species) and megadiverse (more than 1000 species) flowering plant genera and highlight changes since 2004. The number of big genera has increased from 57 to 86; today one of every four plant species is classified as a member of a big genus, with 14% in just 28 megadiverse genera. Most (71%) of the growth in big genera since 2000 is the result of new species description, not generic re-circumscription. More than 15% of all currently accepted flowering plant species described in the last two decades are in big genera, suggesting that groups previously considered intractable are now being actively studied taxonomically. Despite this rapid growth in big genera, they remain a significant yet understudied proportion of plant diversity. They represent a significant proportion of global plant diversity and should remain a priority not only for taxonomy but for understanding global diversity patterns and plant evolution in general.

How to classify antipsychotics: time to ditch dichotomies?

The dichotomies of 'typical/atypical' or 'first/second generation' have been employed for several decades to classify antipsychotics, but justification for their use is not clear. In the current analysis we argue that this classification is flawed from both clinical and pharmacological perspectives. We then consider what approach should ideally be employed in both clinical and research settings.

Formation of prokaryote names from personal names: a review of current practice and a proposal to emend Appendix 9 of the International Code of Nomenclature of Prokaryotes.

The practice of naming elements from the natural world after notable individuals stretches back to ancient times. This practice of creating eponyms-terms derived from personal names-has been carried forward into prokaryotic nomenclature, where the International Code of Nomenclature of Prokaryotes (ICNP) sets guidelines for creating scientific names from personal names. However, these guidelines can be seen as culturally biased, disjointed and, on occasion, misguided. Here, with the goal of modernizing these recommendations to render them more user-friendly, coherent and inclusive, I review current practice in the light of precedents and key linguistic and cultural principles, while questioning the applicability of the first-name/last-name paradigm for many cultural traditions. Procedural challenges include romanization of the personal name (including handling of diacritics), creation of a short and agreeable latinized stem, assignment of the stem to a declension and addition of suffixes or compound word components to create genus names or species epithets, customizing the approach for names and stems that end in a vowel. I review the pros and cons of stem augmentation, which involves addition of an extra 'i' to the original stem. Next, I formulate a coherent workflow, which I incorporate into a Python script to enable computer-based automation of name creation. Rather than following the ICNP in limiting discussion to a few dozen mainly European names, I examine how these principles work out when applied to the tens of thousands of last names under which scientists publish in the PubMed database, focusing on edge cases where conventional approaches fail, particularly very short and very long names. Drawing on these explorations and analyses, I propose emendations to the advice currently presented in the ICNP to usher in a modern, consistent, pragmatic and globally inclusive approach to the creation of prokaryotic eponyms.

Proposals to revise the Statutes of the International Committee on Systematics of Prokaryotes.

The International Committee on Systematics of Prokaryotes serves to administer the rules of prokaryotic nomenclature via the International Code of Nomenclature of Prokaryotes, ensures the publication of the International Journal of Systematic and Evolutionary Microbiology, and works to represent the interests of the microbiological disciplines regarding prokaryotic nomenclature. The functions and mechanisms of operation of the International Committee on Systematics of Prokaryotes (ICSP) are defined in its Statutes, which were last revised in 2019. As members of the 2020-2023 and the 2023-2026 ICSP Executive Board and the Judicial Commission, we propose here some further revisions to help improve the clarity and functionality of the Statutes.

Valid publication of names for bacterial species from the chicken gut.

This article is a follow-up to Gilroy R, Ravi A, Getino M, Pursley I, Horton DL, et al. PeerJ 2021;9:e10941, detailing accession numbers from culture collections to ensure that names for 33 new species conform to the Rules of the International Code of Nomenclature of Prokaryotes required for valid publication of names for cultured species. The following species names are now proposed to be recognized as validly published: Acinetobacter pecorum sp. nov., Arthrobacter gallicola sp. nov., Arthrobacter pullicola sp. nov., Bacillus norwichensis sp. nov., Brevibacterium gallinarum sp. nov., Brevundimonas guildfordensis sp. nov., Cellulomonas avistercoris sp. nov., Clostridium gallinarum sp. nov., Comamonas avium sp. nov., Corynebacterium gallinarum sp. nov., Cytobacillus stercorigallinarum sp. nov., Escherichia whittamii sp. nov., Kaistella pullorum sp. nov., Luteimonas colneyensis sp. nov., Microbacterium commune sp. nov., Microbacterium gallinarum sp. nov., Microbacterium pullorum sp. nov., Oceanitalea stevensii sp. nov., Ochrobactrum gallinarum sp. nov., Oerskovia douganii sp. nov., Oerskovia gallyi sp. nov., Oerskovia merdavium sp. nov., Oerskovia rustica sp. nov., Paenibacillus gallinarum sp. nov., Phocaeicola gallinarum sp. nov., Planococcus wigleyi sp. nov., Psychrobacter communis sp. nov., Serpens gallinarum sp. nov., Solibacillus faecavium sp. nov., Sporosarcina gallistercoris sp. nov., Sporosarcina quadrami sp. nov., Stenotrophomonas pennii sp. nov. and Ureibacillus galli sp. nov.

Judicial Opinion 129.

Opinion 129 addresses the status of Firmicutes corrig. Gibbons and Murray 1978 (Approved Lists 1980). The name has the category 'division' and was included in the Approved Lists of Bacterial Names, although that category had previously been removed from the International Code of Nomenclature of Bacteria (1975 revision onwards). When the category 'phylum' was introduced into the International Code of Nomenclature of Prokaryotes (ICNP) in 2021, equivalence between 'phylum' and 'division' was not stipulated. Since the definition of the taxonomic categories and their relative order is one of the principal tasks of every code of nomenclature, the inclusion of Firmicutes corrig. Gibbons and Murray 1978 in the Approved Lists was an error. The name is either not validly published or illegitimate because its category is not covered by the ICNP. If Firmicutes corrig. Gibbons and Murray 1978 (Approved Lists 1980) was a validly published phylum name, it would be illegitimate because it would contravene Rule 8, which does not permit any deviation from the requirement to derive a phylum name from the name of the type genus. Since Firmicutes corrig. Gibbons and Murray 1978 is also part of a 'misfitting megaclassification' recognized in Opinion 128, the name is rejected, without any pre-emption regarding a hypothetically validly published name Firmicutes at the rank of phylum. Gracilicutes Gibbons and Murray 1978 (Approved Lists 1980) and Anoxyphotobacteriae Gibbons and Murray 1978 (Approved Lists 1980) are also rejected. The validly published phylum names have a variety of advantages over their not validly published counterparts and cannot be replaced with ad hoc names suggested in the literature. To ease the transition, it is recommended to mention the not validly published phylum names which strongly deviate in spelling from their validly published counterparts along with the latter in publications during the next years.

The dynamic history of prokaryotic phyla: discovery, diversity and division.

Here, I review the dynamic history of prokaryotic phyla. Following leads set by Darwin, Haeckel and Woese, the concept of phylum has evolved from a group sharing common phenotypes to a set of organisms sharing a common ancestry, with modern taxonomy based on phylogenetic classifications drawn from macromolecular sequences. Phyla came as surprising latecomers to the formalities of prokaryotic nomenclature in 2021. Since then names have been validly published for 46 prokaryotic phyla, replacing some established names with neologisms, prompting criticism and debate within the scientific community. Molecular barcoding enabled phylogenetic analysis of microbial ecosystems without cultivation, leading to the identification of candidate divisions (or phyla) from diverse environments. The introduction of metagenome-assembled genomes marked a significant advance in identifying and classifying uncultured microbial phyla. The lumper-splitter dichotomy has led to disagreements, with experts cautioning against the pressure to create a profusion of new phyla and prominent databases adopting a conservative stance. The Candidatus designation has been widely used to provide provisional status to uncultured prokaryotic taxa, with phyla named under this convention now clearly surpassing those with validly published names. The Genome Taxonomy Database (GTDB) has offered a stable, standardized prokaryotic taxonomy with normalized taxonomic ranks, which has led to both lumping and splitting of pre-existing phyla. The GTDB framework introduced unwieldy alphanumeric placeholder labels, prompting recent publication of over 100 user-friendly Latinate names for unnamed prokaryotic phyla. Most candidate phyla remain 'known unknowns', with limited knowledge of their genomic diversity, ecological roles, or environments. Whether phyla still reflect significant evolutionary and ecological partitions across prokaryotic life remains an area of active debate. However, phyla remain of practical importance for microbiome analyses, particularly in clinical research. Despite potential diminishing returns in discovery of biodiversity, prokaryotic phyla offer extensive research opportunities for microbiologists for the foreseeable future.

Proposal to add a Note to Rule 8 of the International Code of Nomenclature of Prokaryotes to clarify the meaning of the term 'stem'.

According to the Rules of the International Code of Nomenclature of Prokaryotes (ICNP) and its appendices, names of higher taxa are formed by the addition of the appropriate suffix to the stem of the name of the type genus, and word stems derived from Latin and/or Greek are combined to compound names by means of an appropriate connecting vowel. The way the word 'stem' is used in the ICNP differs from the meaning of this term in textbooks of Latin and Greek grammar. We therefore propose to add a Note to Rule 8, clarifying that the term 'stem' when used in the ICNP corresponds with that part of the word that does not vary among the forms of the noun in the oblique cases, i.e., cases other than the nominative, and which can be obtained by deleting the ending of the genitive singular.

Valid publication of names of two domains and seven kingdoms of prokaryotes.

The International Code of Nomenclature of Prokaryotes (ICNP) now includes the categories domain and kingdom. For the purpose of the valid publication of their names under the ICNP, we consider here the two known domains, 'Bacteria' and 'Archaea', as well as a number of taxa suitable for the rank of kingdom, based on previous phylogenetic and taxonomic studies. It is proposed to subdivide the domain Bacteria into the kingdoms Bacillati, Fusobacteriati, Pseudomonadati and Thermotogati. This arrangement reflects contemporary phylogenetic hypotheses as well as previous taxonomic proposals based on cell wall structure, including 'diderms' vs. 'monoderms', Gracilicutes vs. Firmicutes, 'Negibacteria' vs. 'Unibacteria', 'Hydrobacteria' vs. 'Terrabacteria', and 'Hydrobacterida' vs. 'Terrabacterida'. The domain Archaea is proposed to include the kingdoms Methanobacteriati, Nanobdellati and Thermoproteati, reflecting the previous division into 'Euryarchaeota', 'DPANN superphylum' and 'TACK superphylum'.

Is the bacterial genus name Rhodococcus Zopf 1891 illegitimate? Request for an Opinion.

In 2014, it was reported that the bacterial genus name Rhodococcus Zopf 1891 was illegitimate due to the priority of the cyanobacterial genus name Rhodococcus Hansgirg 1884. Since that time, the consequences of this conclusion have been largely ignored, whilst changes have been made to relevant Rules of the International Code of Nomenclature of Prokaryotes, including significant changes to the way in which the Code treats the names of members of Cyanobacteriota. Given the complexity of the nomenclatural issues, we request the opinion of the Judicial Commission of the International Committee on Systematics of Prokaryotes as to whether the genus name Rhodococcus Zopf 1891 (Approved Lists 1980) is illegitimate.