Multiple Deeply Divergent Denisovan Ancestries in Papuans.

Genome sequences are known for two archaic hominins-Neanderthals and Denisovans-which interbred with anatomically modern humans as they dispersed out of Africa. We identified high-confidence archaic haplotypes in 161 new genomes spanning 14 island groups in Island Southeast Asia and New Guinea and found large stretches of DNA that are inconsistent with a single introgressing Denisovan origin. Instead, modern Papuans carry hundreds of gene variants from two deeply divergent Denisovan lineages that separated over 350 thousand years ago. Spatial and temporal structure among these lineages suggest that introgression from one of these Denisovan groups predominantly took place east of the Wallace line and continued until near the end of the Pleistocene. A third Denisovan lineage occurs in modern East Asians. This regional mosaic suggests considerable complexity in archaic contact, with modern humans interbreeding with multiple Denisovan groups that were geographically isolated from each other over deep evolutionary time.

Denisovan, modern human and mouse TNFAIP3 alleles tune A20 phosphorylation and immunity.

Resisting and tolerating microbes are alternative strategies to survive infection, but little is known about the evolutionary mechanisms controlling this balance. Here genomic analyses of anatomically modern humans, extinct Denisovan hominins and mice revealed a TNFAIP3 allelic series with alterations in the encoded immune response inhibitor A20. Each TNFAIP3 allele encoded substitutions at non-catalytic residues of the ubiquitin protease OTU domain that diminished IκB kinase-dependent phosphorylation and activation of A20. Two TNFAIP3 alleles encoding A20 proteins with partial phosphorylation deficits seemed to be beneficial by increasing immunity without causing spontaneous inflammatory disease: A20 T108A;I207L, originating in Denisovans and introgressed in modern humans throughout Oceania, and A20 I325N, from an N-ethyl-N-nitrosourea (ENU)-mutagenized mouse strain. By contrast, a rare human TNFAIP3 allele encoding an A20 protein with 95% loss of phosphorylation, C243Y, caused spontaneous inflammatory disease in humans and mice. Analysis of the partial-phosphorylation A20 I325N allele in mice revealed diminished tolerance of bacterial lipopolysaccharide and poxvirus inoculation as tradeoffs for enhanced immunity.

Regulation of Bacterial Ribonucleases.

Ribonucleases (RNases) are essential for almost every aspect of RNA metabolism. However, despite their important metabolic roles, RNases can also be destructive enzymes. As a consequence, cells must carefully regulate the amount, the activity, and the localization of RNases to avoid the inappropriate degradation of essential RNA molecules. In addition, bacterial cells often must adjust RNase levels as environmental situations demand, also requiring careful regulation of these critical enzymes. As the need for strict control of RNases has become more evident, multiple mechanisms for this regulation have been identified and studied, and these are described in this review. The major conclusion that emerges is that no common regulatory mechanism applies to all RNases, or even to a family of RNases; rather, a wide variety of processes have evolved that act on these enzymes, and in some cases, multiple regulatory mechanisms can even act on a single RNase.

Genetic architecture of gene regulation in Indonesian populations identifies QTLs associated with global and local ancestries.

Lack of diversity in human genomics limits our understanding of the genetic underpinnings of complex traits, hinders precision medicine, and contributes to health disparities. To map genetic effects on gene regulation in the underrepresented Indonesian population, we have integrated genotype, gene expression, and CpG methylation data from 115 participants across three island populations that capture the major sources of genomic diversity in the region. In a comparison with European datasets, we identify eQTLs shared between Indonesia and Europe as well as population-specific eQTLs that exhibit differences in allele frequencies and/or overall expression levels between populations. By combining local ancestry and archaic introgression inference with eQTLs and methylQTLs, we identify regulatory loci driven by modern Papuan ancestry as well as introgressed Denisovan and Neanderthal variation. GWAS colocalization connects QTLs detected here to hematological traits, and further comparison with European datasets reflects the poor overall transferability of GWAS statistics across diverse populations. Our findings illustrate how population-specific genetic architecture, local ancestry, and archaic introgression drive variation in gene regulation across genetically distinct and in admixed populations and highlight the need for performing association studies on non-European populations.

Denisovan introgression has shaped the immune system of present-day Papuans.

Modern humans have admixed with multiple archaic hominins. Papuans, in particular, owe up to 5% of their genome to Denisovans, a sister group to Neanderthals whose remains have only been identified in Siberia and Tibet. Unfortunately, the biological and evolutionary significance of these introgression events remain poorly understood. Here we investigate the function of both Denisovan and Neanderthal alleles characterised within a set of 56 genomes from Papuan individuals. By comparing the distribution of archaic and non-archaic variants we assess the consequences of archaic admixture across a multitude of different cell types and functional elements. We observe an enrichment of archaic alleles within cis-regulatory elements and transcribed regions of the genome, with Denisovan variants strongly affecting elements active within immune-related cells. We identify 16,048 and 10,032 high-confidence Denisovan and Neanderthal variants that fall within annotated cis-regulatory elements and with the potential to alter the affinity of multiple transcription factors to their cognate DNA motifs, highlighting a likely mechanism by which introgressed DNA can impact phenotypes. Lastly, we experimentally validate these predictions by testing the regulatory potential of five Denisovan variants segregating within Papuan individuals, and find that two are associated with a significant reduction of transcriptional activity in plasmid reporter assays. Together, these data provide support for a widespread contribution of archaic DNA in shaping the present levels of modern human genetic diversity, with different archaic ancestries potentially affecting multiple phenotypic traits within non-Africans.

Episodes of Diversification and Isolation in Island Southeast Asian and Near Oceanian Male Lineages.

Island Southeast Asia (ISEA) and Oceania host one of the world's richest assemblages of human phenotypic, linguistic, and cultural diversity. Despite this, the region's male genetic lineages are globally among the last to remain unresolved. We compiled ∼9.7 Mb of Y chromosome (chrY) sequence from a diverse sample of over 380 men from this region, including 152 first reported here. The granularity of this data set allows us to fully resolve and date the regional chrY phylogeny. This new high-resolution tree confirms two main population bursts: multiple rapid diversifications following the region's initial settlement ∼50 kya, and extensive expansions <6 kya. Notably, ∼40-25 kya the deep rooting local lineages of C-M130, M-P256, and S-B254 show almost no further branching events in ISEA, New Guinea, and Australia, matching a similar pause in diversification seen in maternal mitochondrial DNA lineages. The main local lineages start diversifying ∼25 kya, at the time of the last glacial maximum. This improved chrY topology highlights localized events with important historical implications, including pre-Holocene contact between Mainland and ISEA, potential interactions between Australia and the Papuan world, and a sustained period of diversification following the flooding of the ancient Sunda and Sahul continents as the insular landscape observed today formed. The high-resolution phylogeny of the chrY presented here thus enables a detailed exploration of past isolation, interaction, and change in one of the world's least understood regions.

The Bcvic1 and Bcvic2 vegetative incompatibility genes in Botrytis cinerea encode proteins with domain architectures involved in allorecognition in other filamentous fungi.

Vegetative incompatibility is a fungal allorecognition system characterised by the inability of genetically distinct conspecific fungal strains to form a viable heterokaryon and is controlled by multiple polymorphic loci termed vic (vegetative incompatibility) or het (heterokaryon incompatibility). We have genetically identified and characterised the first vic locus in the economically important, plant-pathogenic, necrotrophic fungus Botrytis cinerea. A bulked segregant approach coupled with whole genome Illumina sequencing of near-isogenic lines of B. cinerea was used to map a vic locus to a 60-kb region of the genome. Within that locus, we identified two adjacent, highly polymorphic open reading frames, Bcvic1 and Bcvic2, which encode predicted proteins that contain domain architectures implicated in vegetative incompatibility in other filamentous fungi. Bcvic1 encodes a predicted protein containing a putative serine esterase domain, a NACHT family of NTPases domain, and several Ankyrin repeats. Bcvic2 encodes a putative syntaxin protein containing a SNARE domain; such proteins typically function in vesicular transport. Deletion of Bcvic1 and Bcvic2 individually had no effect on vegetative incompatibility. However, deletion of the region containing both Bcvic1 and Bcvic2 resulted in mutant lines that were severely restricted in growth and showed loss of vegetative incompatibility. Complementation of these mutants by ectopic expression restored the growth and vegetative incompatibility phenotype, indicating that Bcvic1 and Bcvic2 are controlling vegetative incompatibility at this vic locus.

A role for REP sequences in regulating translation.

Repetitive extragenic palindromic (REP) sequences are highly structured elements found downstream of ∼500 genes in Escherichia coli that result in extensive stem-loop structures in their mRNAs. However, their physiological role has remained elusive. Here, we show that REP sequences can downregulate translation, but only if they are within 15 nt of a termination codon; a spacing of 16 nt has no effect, suggesting that the REP element acts to stall ribosome movement. Ribosome stalling leads to cleavage of the mRNA and induction of the trans-translation process. Using nrdAB as a model, we find that its regulation can be partially reversed by overexpression of RNA helicases and can be fully overcome upon UV stress, emphasizing the importance of this regulatory process. Since 50% of REP-associated genes have these elements within the critical 15 nt, these findings identify a regulatory mechanism with the potential to affect translation from a large number of genes.

Genome-wide DNA methylation and gene expression patterns reflect genetic ancestry and environmental differences across the Indonesian archipelago.

Indonesia is the world's fourth most populous country, host to striking levels of human diversity, regional patterns of admixture, and varying degrees of introgression from both Neanderthals and Denisovans. However, it has been largely excluded from the human genomics sequencing boom of the last decade. To serve as a benchmark dataset of molecular phenotypes across the region, we generated genome-wide CpG methylation and gene expression measurements in over 100 individuals from three locations that capture the major genomic and geographical axes of diversity across the Indonesian archipelago. Investigating between- and within-island differences, we find up to 10.55% of tested genes are differentially expressed between the islands of Sumba and New Guinea. Variation in gene expression is closely associated with DNA methylation, with expression levels of 9.80% of genes correlating with nearby promoter CpG methylation, and many of these genes being differentially expressed between islands. Genes identified in our differential expression and methylation analyses are enriched in pathways involved in immunity, highlighting Indonesia's tropical role as a source of infectious disease diversity and the strong selective pressures these diseases have exerted on humans. Finally, we identify robust within-island variation in DNA methylation and gene expression, likely driven by fine-scale environmental differences across sampling sites. Together, these results strongly suggest complex relationships between DNA methylation, transcription, archaic hominin introgression and immunity, all jointly shaped by the environment. This has implications for the application of genomic medicine, both in critically understudied Indonesia and globally, and will allow a better understanding of the interacting roles of genomic and environmental factors shaping molecular and complex phenotypes.

Reconstruction of gene innovation associated with major evolutionary transitions in the kingdom Fungi.

BACKGROUND: Fungi exhibit astonishing diversity with multiple major phenotypic transitions over the kingdom's evolutionary history. As part of this process, fungi developed hyphae, adapted to land environments (terrestrialization), and innovated their sexual structures. These changes also helped fungi establish ecological relationships with other organisms (animals and plants), but the genomic basis of these changes remains largely unknown. RESULTS: By systematically analyzing 304 genomes from all major fungal groups, together with a broad range of eukaryotic outgroups, we have identified 188 novel orthogroups associated with major changes during the evolution of fungi. Functional annotations suggest that many of these orthogroups were involved in the formation of key trait innovations in extant fungi and are functionally connected. These innovations include components for cell wall formation, functioning of the spindle pole body, polarisome formation, hyphal growth, and mating group signaling. Innovation of mitochondria-localized proteins occurred widely during fungal transitions, indicating their previously unrecognized importance. We also find that prokaryote-derived horizontal gene transfer provided a small source of evolutionary novelty with such genes involved in key metabolic pathways. CONCLUSIONS: The overall picture is one of a relatively small number of novel genes appearing at major evolutionary transitions in the phylogeny of fungi, with most arising de novo and horizontal gene transfer providing only a small additional source of evolutionary novelty. Our findings contribute to an increasingly detailed portrait of the gene families that define fungal phyla and underpin core features of extant fungi.

The Venturia inaequalis effector repertoire is dominated by expanded families with predicted structural similarity, but unrelated sequence, to avirulence proteins from other plant-pathogenic fungi.

BACKGROUND: Scab, caused by the biotrophic fungus Venturia inaequalis, is the most economically important disease of apples worldwide. During infection, V. inaequalis occupies the subcuticular environment, where it secretes virulence factors, termed effectors, to promote host colonization. Consistent with other plant-pathogenic fungi, many of these effectors are expected to be non-enzymatic proteins, some of which can be recognized by corresponding host resistance proteins to activate plant defences, thus acting as avirulence determinants. To develop durable control strategies against scab, a better understanding of the roles that these effector proteins play in promoting subcuticular growth by V. inaequalis, as well as in activating, suppressing, or circumventing resistance protein-mediated defences in apple, is required. RESULTS: We generated the first comprehensive RNA-seq transcriptome of V. inaequalis during colonization of apple. Analysis of this transcriptome revealed five temporal waves of gene expression that peaked during early, mid, or mid-late infection. While the number of genes encoding secreted, non-enzymatic proteinaceous effector candidates (ECs) varied in each wave, most belonged to waves that peaked in expression during mid-late infection. Spectral clustering based on sequence similarity determined that the majority of ECs belonged to expanded protein families. To gain insights into function, the tertiary structures of ECs were predicted using AlphaFold2. Strikingly, despite an absence of sequence similarity, many ECs were predicted to have structural similarity to avirulence proteins from other plant-pathogenic fungi, including members of the MAX, LARS, ToxA and FOLD effector families. In addition, several other ECs, including an EC family with sequence similarity to the AvrLm6 avirulence effector from Leptosphaeria maculans, were predicted to adopt a KP6-like fold. Thus, proteins with a KP6-like fold represent another structural family of effectors shared among plant-pathogenic fungi. CONCLUSIONS: Our study reveals the transcriptomic profile underpinning subcuticular growth by V. inaequalis and provides an enriched list of ECs that can be investigated for roles in virulence and avirulence. Furthermore, our study supports the idea that numerous sequence-unrelated effectors across plant-pathogenic fungi share common structural folds. In doing so, our study gives weight to the hypothesis that many fungal effectors evolved from ancestral genes through duplication, followed by sequence diversification, to produce sequence-unrelated but structurally similar proteins.

Papua New Guinean Genomes Reveal the Complex Settlement of North Sahul.

The settlement of Sahul, the lost continent of Oceania, remains one of the most ancient and debated human migrations. Modern New Guineans inherited a unique genetic diversity tracing back 50,000 years, and yet there is currently no model reconstructing their past population dynamics. We generated 58 new whole-genome sequences from Papua New Guinea, filling geographical gaps in previous sampling, specifically to address alternative scenarios of the initial migration to Sahul and the settlement of New Guinea. Here, we present the first genomic models for the settlement of northeast Sahul considering one or two migrations from Wallacea. Both models fit our data set, reinforcing the idea that ancestral groups to New Guinean and Indigenous Australians split early, potentially during their migration in Wallacea where the northern route could have been favored. The earliest period of human presence in Sahul was an era of interactions and gene flow between related but already differentiated groups, from whom all modern New Guineans, Bismarck islanders, and Indigenous Australians descend. The settlement of New Guinea was probably initiated from its southeast region, where the oldest archaeological sites have been found. This was followed by two migrations into the south and north lowlands that ultimately reached the west and east highlands. We also identify ancient gene flows between populations in New Guinea, Australia, East Indonesia, and the Bismarck Archipelago, emphasizing the fact that the anthropological landscape during the early period of Sahul settlement was highly dynamic rather than the traditional view of extensive isolation.

Breaking Free: The Genomics of Allopolyploidy-Facilitated Niche Expansion in White Clover.

The merging of distinct genomes, allopolyploidization, is a widespread phenomenon in plants. It generates adaptive potential through increased genetic diversity, but examples demonstrating its exploitation remain scarce. White clover (Trifolium repens) is a ubiquitous temperate allotetraploid forage crop derived from two European diploid progenitors confined to extreme coastal or alpine habitats. We sequenced and assembled the genomes and transcriptomes of this species complex to gain insight into the genesis of white clover and the consequences of allopolyploidization. Based on these data, we estimate that white clover originated ∼15,000 to 28,000 years ago during the last glaciation when alpine and coastal progenitors were likely colocated in glacial refugia. We found evidence of progenitor diversity carryover through multiple hybridization events and show that the progenitor subgenomes have retained integrity and gene expression activity as they traveled within white clover from their original confined habitats to a global presence. At the transcriptional level, we observed remarkably stable subgenome expression ratios across tissues. Among the few genes that show tissue-specific switching between homeologous gene copies, we found flavonoid biosynthesis genes strongly overrepresented, suggesting an adaptive role of some allopolyploidy-associated transcriptional changes. Our results highlight white clover as an example of allopolyploidy-facilitated niche expansion, where two progenitor genomes, adapted and confined to disparate and highly specialized habitats, expanded to a ubiquitous global presence after glaciation-associated allopolyploidization.

Cross-kingdom transcriptomic trends in the evolution of hybrid gene expression.

Hybridization is a route to speciation that occurs widely across the eukaryote tree of life. The success of allopolyploids (hybrid species with increased ploidy) and homoploid hybrids (with unchanged ploidy) is well documented. However, their formation and establishment is not straightforward, with a suite of near-instantaneous and longer term biological repercussions faced by the new species. Central to these challenges is the rewiring of gene regulatory networks following the merger of distinct genomes inherited from both parental species. Research on the evolution of hybrid gene expression has largely involved studies on a single hybrid species or a few gene families. Here, we present the first standardized transcriptome-wide study exploring the fates of genes following hybridization across three kingdoms: animals, plants and fungi. Within each kingdom, we pair an allopolyploid system with a closely related homoploid hybrid to decouple the influence of increased ploidy from genome merger. Genome merger, not changes in ploidy, has the greatest effect on posthybridization expression patterns across all study systems. Strikingly, we find that differentially expressed genes in parent species preferentially switch to more similar expression in hybrids across all kingdoms, likely as a consequence of regulatory trans-acting cross-talk within the hybrid nucleus. We also highlight the prevalence of gene loss or silencing among extremely differentially expressed genes in hybrid species across all kingdoms. These shared patterns suggest that the evolutionary process of hybridization leads to common high-level expression outcomes, regardless of the particular species or kingdom.

Genomic insights into the peopling of the Southwest Pacific.

The appearance of people associated with the Lapita culture in the South Pacific around 3,000 years ago marked the beginning of the last major human dispersal to unpopulated lands. However, the relationship of these pioneers to the long-established Papuan people of the New Guinea region is unclear. Here we present genome-wide ancient DNA data from three individuals from Vanuatu (about 3,100-2,700 years before present) and one from Tonga (about 2,700-2,300 years before present), and analyse them with data from 778 present-day East Asians and Oceanians. Today, indigenous people of the South Pacific harbour a mixture of ancestry from Papuans and a population of East Asian origin that no longer exists in unmixed form, but is a match to the ancient individuals. Most analyses have interpreted the minimum of twenty-five per cent Papuan ancestry in the region today as evidence that the first humans to reach Remote Oceania, including Polynesia, were derived from population mixtures near New Guinea, before their further expansion into Remote Oceania. However, our finding that the ancient individuals had little to no Papuan ancestry implies that later human population movements spread Papuan ancestry through the South Pacific after the first peopling of the islands.

Chromosome-level genomes provide insights into genome evolution, organization and size in Epichloe fungi.

Epichloe fungi are endophytes of cool season grasses, both wild species and commercial cultivars, where they may exhibit mutualistic or pathogenic lifestyles. The Epichloe-grass symbiosis is of great interest to agricultural research for the fungal bioprotective properties conferred to host grasses but also serves as an ideal system to study the evolution of fungal plant-pathogens in natural environments. Here, we assembled and annotated gapless chromosome-level genomes of two pathogenic Epichloe sibling species. Both genomes have a bipartite genome organization, with blocks of highly syntenic gene-rich regions separated by blocks of AT-rich DNA. The AT-rich regions show an extensive signature of RIP (repeat-induced point mutation) and the expansion of this compartment accounts for the large difference in genome size between the two species. This study reveals how the rapid evolution of repeat structure can drive divergence between closely related taxa and highlights the evolutionary role of dynamic compartments in fungal genomes.

Distal urethral carcinoma: Contemporary management with phallus preserving techniques.

INTRODUCTION: Primary urethral carcinoma is a rare clinical entity with an incidence of 1 case per million in the United Kingdom. Cancers of the distal urethra are most commonly of squamous subtype and often associated with Human Papilloma Virus infection. Penile preserving techniques are recommended in tumours of the pendulous urethra with a number of surgical approaches described. Herein, we describe the surgical management of 7 patients presenting with primary urethral carcinoma. METHODS: Seven patients diagnosed with primary urethral carcinoma of the distal urethra were identified using a prospectively maintained penile cancer database at our institution from May 2017 to November 2020. RESULTS: The mean age at presentation was 56.5 (33-80) years. Presenting symptoms included visible lesion, LUTS and a groin mass. Three patients had lesions located within the glanular urethra and had a distal urethrectomy and primary closure. Two patients with lesions extending proximal to the glanular urethra and into or beyond the fossa navicularis had a distal urethrectomy with a hypospadic neomeatus formation. One patient with tumour extending into the glans penis underwent distal urethrectomy and partial glansectomy with split thickness skin graft. A partial penectomy was performed for one patient with urethral tumour invading the corporal heads. Mean follow-up was 23.4 (±17.0) months. There have been no disease recurrences to date. CONCLUSION: Penile preserving techniques are feasible in patients with tumours of the pendulous urethra and do not appear to compromise local control.

Opportunities for Education in Heart Failure Pharmacotherapy Demonstrated by a Survey of Clinicians.

Aim We conducted a survey of practitioners' knowledge of the clinical application of the major drug classes in HF, with reference to the European Society of Cardiology guidelines. The aim was to identify areas for practice development through education, which may improve HF morbidity and mortality. Methods We distributed a 14 item questionnaire assessing doctors knowledge of indications and contraindications for the major HF drug classes. Results Total number of responses was 127: Intern (N=21), SHO (N=64), Registrar (N=12), SpR (N=14), Consultant (N=4), GP (N=2). Consultants and GPs were excluded from analysis due to underrepresentation. Median years of practice was 4. Indications were correctly identified in a mean of 78% of responses overall. Of participants who felt comfortable with initiation and up-titration of beta blockers (N=84), only 31% (N=26) correctly identified an optimal target heart rate of less than 70 beats per minute. Forty-five percent (N=50) identified serum potassium and creatinine concentrations generally considered safe as contraindications to the initiation of MRA. Twenty-five percent of respondents (N=28) were unaware of a specialist HF service that catered to their institution, and how to refer to it, but 99% (N=110) felt that their practice would benefit from further education on HF pharmacotherapy. Conclusion Results of this survey suggest a need, and indeed a demand, for further education for clinicians in order to reduce mortality, morbidity, and hospital readmission in HF, as well as their attendant costs.

Persisting Symptomatic Severe Secondary Mitral Regurgitation in Heart Failure Patients.

Aims We aimed to assess the rate of persisting severe symptomatic secondary mitral regurgitation (MR) in a newly diagnosed heart failure (HF) population following optimisation of guideline directed medical therapy (GDMT), cardiac resynchronisation therapy (CRT) and revascularisation. Methods We assessed all new patients referred to our hospital group's HF clinics. We retrospectively reviewed these patients at HF clinic enrolment, HF programme completion, as well as most recent follow up. Results Of the 242 new patients referred to our HF clinics, there were 10 patients (4.1%) who had either persisting symptomatic severe secondary MR at HF programme completion, or had undergone mitral valve surgery. There were no percutaneous mitral valve repairs at the time of these patients' referrals. The rates of ACE/ARB/ARNI, BB and MRA use were 87.8%, 94.1%, and 49.8% in those with mid ranged, or reduced ejection fraction. The rates of ICD and CRT therapy were 15.1% and 4.4% at follow up. Patients with severe MR had higher time adjusted rates of death or hospitalization for heart failure. Conclusion In a well-treated newly diagnosed HF population, repeat assessment at HF programme completion suggests 4.1% of patients have a persisting indication for percutaneous mitral valve repair based on persisting severe symptomatic secondary MR.

Bacterial ribonucleases and their roles in RNA metabolism.

Ribonucleases (RNases) are mediators in most reactions of RNA metabolism. In recent years, there has been a surge of new information about RNases and the roles they play in cell physiology. In this review, a detailed description of bacterial RNases is presented, focusing primarily on those from Escherichia coli and Bacillus subtilis, the model Gram-negative and Gram-positive organisms, from which most of our current knowledge has been derived. Information from other organisms is also included, where relevant. In an extensive catalog of the known bacterial RNases, their structure, mechanism of action, physiological roles, genetics, and possible regulation are described. The RNase complement of E. coli and B. subtilis is compared, emphasizing the similarities, but especially the differences, between the two. Included are figures showing the three major RNA metabolic pathways in E. coli and B. subtilis and highlighting specific steps in each of the pathways catalyzed by the different RNases. This compilation of the currently available knowledge about bacterial RNases will be a useful tool for workers in the RNA field and for others interested in learning about this area.