Terminal regions of a protein are a hotspot for low complexity regions and selection.

Volatile low complexity regions (LCRs) are a novel source of adaptive variation, functional diversification and evolutionary novelty. An interplay of selection and mutation governs the composition and length of low complexity regions. High %GC and mutations provide length variability because of mechanisms like replication slippage. Owing to the complex dynamics between selection and mutation, we need a better understanding of their coexistence. Our findings underscore that positively selected sites (PSS) and low complexity regions prefer the terminal regions of genes, co-occurring in most Tetrapoda clades. We observed that positively selected sites within a gene have position-specific roles. Central-positively selected site genes primarily participate in defence responses, whereas terminal-positively selected site genes exhibit non-specific functions. Low complexity region-containing genes in the Tetrapoda clade exhibit a significantly higher %GC and lower ω (dN/dS: non-synonymous substitution rate/synonymous substitution rate) compared with genes without low complexity regions. This lower ω implies that despite providing rapid functional diversity, low complexity region-containing genes are subjected to intense purifying selection. Furthermore, we observe that low complexity regions consistently display ubiquitous prevalence at lower purity levels, but exhibit a preference for specific positions within a gene as the purity of the low complexity region stretch increases, implying a composition-dependent evolutionary role. Our findings collectively contribute to the understanding of how genetic diversity and adaptation are shaped by the interplay of selection and low complexity regions in the Tetrapoda clade.

Genomic and Transcriptomic Analyses Illuminates Unique Traits of Elusive Night Flowering Jasmine Parijat (Nyctanthes arbor-tristis).

The night-flowering Jasmine, Nyctanthes arbor-tristis also known as Parijat, is a perennial woody shrub belonging to the family of Oleaceae. It is popular for its fragrant flowers that bloom in the night and is a potent source of secondary metabolites. However, knowledge about its genome and the expression of genes regulating flowering or secondary metabolite accumulation is lacking. In this study, we generated whole genome sequencing data to assemble the first de novo assembly of Parijat and use it for comparative genomics and demographic history reconstruction. The temporal dynamics of effective population size (Ne ) experienced a positive influence of colder climates suggesting the switch to night flowering may have provided an evolutionary advantage. We employed multi-tissue transcriptome sequencing of floral stages/parts to obtain insights into the transcriptional regulation of nocturnal flower development and the production of volatiles/metabolites. Tissue-specific transcripts for mature flowers revealed key players in circadian regulation and flower development, including the auxin pathway and cell wall modifying genes. Furthermore, we identified tissue-specific transcripts responsible for producing numerous secondary metabolites, mainly terpenoids and carotenoids. The diversity and specificity of Terpene Synthase (TPS) and CCDs (Carotenoid Cleavage Deoxygenases) mediate the bio-synthesis of specialised metabolites in Parijat. Our study establishes Parijat as a novel non-model species to understand the molecular mechanisms of nocturnal blooming and secondary metabolite production.

HIV-1 Vpr induces ciTRAN to prevent transcriptional repression of the provirus.

The functional consequences of circular RNA (circRNA) expression on HIV-1 replication are largely unknown. Using a customized protocol involving direct RNA nanopore sequencing, here, we captured circRNAs from HIV-1-infected T cells and identified ciTRAN, a circRNA that modulates HIV-1 transcription. We found that HIV-1 infection induces ciTRAN expression in a Vpr-dependent manner and that ciTRAN interacts with SRSF1, a protein known to repress HIV-1 transcription. Our results suggest that HIV-1 hijacks ciTRAN to exclude serine/arginine-rich splicing factor 1 (SRSF1) from the viral transcriptional complex, thereby promoting efficient viral transcription. In addition, we demonstrate that an SRSF1-inspired mimic can inhibit viral transcription regardless of ciTRAN induction. The hijacking of a host circRNA thus represents a previously unknown facet of primate lentiviruses in overcoming transmission bottlenecks.

Concurrent loss of ciliary genes WDR93 and CFAP46 in phylogenetically distant birds.

The respiratory system is the primary route of infection for many contagious pathogens. Mucociliary clearance of inhaled pathogens is an important innate defence mechanism sustained by the rhythmic movement of epithelial cilia. To counter host defences, viral pathogens target epithelial cells and cilia. For instance, the avian influenza virus that targets ciliated cells modulates the expression of WDR93, a central ciliary apparatus C1d projection component. Lineage-specific prevalence of such host defence genes results in differential susceptibility. In this study, the comparative analysis of approximately 500 vertebrate genomes from seven taxonomic classes spanning 73 orders confirms the widespread conservation of WDR93 across these different vertebrate groups. However, we established loss of the WDR93 in landfowl, geese and other phylogenetically independent bird species due to gene-disrupting changes. The lack of WDR93 transcripts in species with gene loss in contrast to its expression in species with an intact gene confirms gene loss. Notably, species with WDR93 loss have concurrently lost another C1d component, CFAP46, through large segmental deletions. Understanding the consequences of such gene loss may provide insight into their role in host-pathogen interactions and benefit global pathogen surveillance efforts by prioritizing species missing host defence genes and identifying putative zoonotic reservoirs.

Decoding the fibromelanosis locus complex chromosomal rearrangement of black-bone chicken: genetic differentiation, selective sweeps and protein-coding changes in Kadaknath chicken.

Black-bone chicken (BBC) meat is popular for its distinctive taste and texture. A complex chromosomal rearrangement at the fibromelanosis (Fm) locus on the 20th chromosome results in increased endothelin-3 (EDN3) gene expression and is responsible for melanin hyperpigmentation in BBC. We use public long-read sequencing data of the Silkie breed to resolve high-confidence haplotypes at the Fm locus spanning both Dup1 and Dup2 regions and establish that the Fm_2 scenario is correct of the three possible scenarios of the complex chromosomal rearrangement. The relationship between Chinese and Korean BBC breeds with Kadaknath native to India is underexplored. Our data from whole-genome re-sequencing establish that all BBC breeds, including Kadaknath, share the complex chromosomal rearrangement junctions at the fibromelanosis (Fm) locus. We also identify two Fm locus proximal regions (∼70 Kb and ∼300 Kb) with signatures of selection unique to Kadaknath. These regions harbor several genes with protein-coding changes, with the bactericidal/permeability-increasing-protein-like gene having two Kadaknath-specific changes within protein domains. Our results indicate that protein-coding changes in the bactericidal/permeability-increasing-protein-like gene hitchhiked with the Fm locus in Kadaknath due to close physical linkage. Identifying this Fm locus proximal selective sweep sheds light on the genetic distinctiveness of Kadaknath compared to other BBC.

Jack of all trades: Genome assembly of Wild Jack and comparative genomics of Artocarpus.

Artocarpus (Moraceae), known as breadfruits for their diverse nutritious fruits, is prized for its high-quality timber, medicinal value, and economic importance. Breadfruits are native to Southeast Asia but have been introduced to other continents. The most commonly cultivated species are Artocarpus heterophyllus (Jackfruit) and Artocarpus altilis (Breadfruit). With numerous smaller but nutritionally comparable fruits on a larger tree, Artocarpus hirsutus, also called "Wild Jack" or "Ayani", is an elusive forest species endemic to Indian Western Ghats. In this study, we sequenced and assembled the whole genome of Artocarpus hirsutus sampled from the sacred groves of Coorg, India. To decipher demographic and evolutionary history, we compared our Wild Jack genome with previously published Jackfruit and Breadfruit genomes. Demographic history reconstruction indicates a stronger effect of habitat rather than phylogeny on the population histories of these plants. Repetitive genomic regions, especially LTR Copia, strongly affected the demographic trajectory of A. heterophyllus. Upon further investigation, we found a recent lineage-specific accumulation of LTR Copia in A. heterophyllus, which had a major contribution to its larger genome size. Several genes from starch, sucrose metabolism, and plant hormone signal transduction pathways, in Artocarpus species had signatures of selection and gene family evolution. Our comparative genomic framework provides important insights by incorporating endemic species such as the Wild Jack.

Lineage-specific protein repeat expansions and contractions reveal malleable regions of immune genes.

Functional diversification, a higher evolutionary rate, and intense positive selection help a limited number of immune genes interact with many pathogens. Repeats in protein-coding regions are a well-known source of functional diversification, adaptive variation, and evolutionary novelty in a short time. Repeats play a crucial role in biochemical functions like functional diversification of transcription regulation, protein kinases, cell adhesion, signaling pathways, morphogenesis, DNA repair, recombination, and RNA processing. Repeat length variation can change the associated protein's interaction, efficacy, and overall protein network. Repeats have an intrinsic unstable nature and can potentially evolve rapidly and expedite the acquisition of complex phenotypic traits and functions. Because of their ability to generate rapid, adaptive variations over short evolutionary distances, repeats are considered "tuning knobs." Repeat length variation in specific genes, like RUNX2 and ALX4, is associated with morphological and physiological changes across vertebrates. Here we study repeat length variation as a potent source of species-specific immune diversification across several clades of tetrapods. Moreover, we provide a clade-wise comprehensive list of immune genes with repeat types for future studies of morphological/evolutionary changes within species groups. We observe significant repeat length variation of FASLG and C1QC in Rodentia and Primates' contrasting species groups, respectively.

Birth and death in terminal complement pathway.

The cytolytic activity of the membrane attack complex (MAC) is pivotal in the complement-mediated elimination of pathogens. Terminal complement pathway (TCP) genes encode the proteins that form the MAC. Although the TCP genes are well conserved within most vertebrate species, the early evolution of the TCP genes is poorly understood. Based on the comparative genomic analysis of the early evolutionary history of the TCP homologs, we evaluated four possible scenarios that could have given rise to the vertebrate TCP. Currently available genomic data support a scheme of complex sequential protein domain gains that may be responsible for the birth of the vertebrate C6 gene. The subsequent duplication and divergence of this vertebrate C6 gene formed the C7, C8α, C8ß, and C9 genes. Compared to the widespread conservation of TCP components within vertebrates, we discovered that C9 has disintegrated in the genomes of galliform birds. Publicly available genome and transcriptome sequencing datasets of chicken from Illumina short read, PacBio long read, and Optical mapping technologies support the validity of the genome assembly at the C9 locus. In this study, we have generated a > 120X coverage whole-genome Chromium 10x linked-read sequencing dataset for the chicken and used it to verify the loss of the C9 gene in the chicken. We find multiple CR1 (chicken repeat 1) element insertions within and near the remnant exons of C9 in several galliform bird genomes. The reconstructed chronology of events shows that the CR1 insertions occurred after C9 gene loss in an early galliform ancestor. Loss of C9 in galliform birds, in contrast to conservation in other vertebrates, may have implications for host-pathogen interactions. Our study of C6 gene birth in an early vertebrate ancestor and C9 gene death in galliform birds provides insights into the evolution of the TCP.

Recurrent erosion of COA1/MITRAC15 exemplifies conditional gene dispensability in oxidative phosphorylation.

Skeletal muscle fibers rely upon either oxidative phosphorylation or the glycolytic pathway with much less reliance on oxidative phosphorylation to achieve muscular contractions that power mechanical movements. Species with energy-intensive adaptive traits that require sudden bursts of energy have a greater dependency on glycolytic fibers. Glycolytic fibers have decreased reliance on OXPHOS and lower mitochondrial content compared to oxidative fibers. Hence, we hypothesized that gene loss might have occurred within the OXPHOS pathway in lineages that largely depend on glycolytic fibers. The protein encoded by the COA1/MITRAC15 gene with conserved orthologs found in budding yeast to humans promotes mitochondrial translation. We show that gene disrupting mutations have accumulated within the COA1 gene in the cheetah, several species of galliform birds, and rodents. The genomic region containing COA1 is a well-established evolutionary breakpoint region in mammals. Careful inspection of genome assemblies of closely related species of rodents and marsupials suggests two independent COA1 gene loss events co-occurring with chromosomal rearrangements. Besides recurrent gene loss events, we document changes in COA1 exon structure in primates and felids. The detailed evolutionary history presented in this study reveals the intricate link between skeletal muscle fiber composition and the occasional dispensability of the chaperone-like role of the COA1 gene.

Repetitive genomic regions and the inference of demographic history.

Inference of demographic histories using whole-genome datasets has provided insights into diversification, adaptation, hybridization, and plant-pathogen interactions, and stimulated debate on the impact of anthropogenic interventions and past climate on species demography. However, the impact of repetitive genomic regions on these inferences has mostly been ignored by masking of repeats. We use the Populus trichocarpa genome (Pop_tri_v3) to show that masking of repeat regions leads to lower estimates of effective population size (Ne) in the distant past in contrast to an increase in Ne estimates in recent times. However, in human datasets, masking of repeats resulted in lower estimates of Ne at all time points. We demonstrate that repeats affect demographic inferences using diverse methods like PSMC, MSMC, SMC++, and the Stairway plot. Our genomic analysis revealed that the biases in Ne estimates were dependent on the repeat class type and its abundance in each atomic interval. Notably, we observed a weak, yet consistently significant negative correlation between the repeat abundance of an atomic interval and the Ne estimates for that interval, which potentially reflects the recombination rate variation within the genome. The rationale for the masking of repeats has been that variants identified within these regions are erroneous. We find that polymorphisms in some repeat classes occur in callable regions and reflect reliable coalescence histories (e.g., LTR Gypsy, LTR Copia). The current demography inference methods do not handle repeats explicitly, and hence the effect of individual repeat classes needs careful consideration in comparative analysis. Deciphering the repeat demographic histories might provide a clear understanding of the processes involved in repeat accumulation.

Coelacanth SERINC2 Inhibits HIV-1 Infectivity and Is Counteracted by Envelope Glycoprotein from Foamy Virus.

SERINC5 restricts nef-defective HIV-1 by affecting early steps of the virus life cycle. Distantly related retroviruses with a wide host range encode virulent factors in response to challenge by SERINC5. However, the evolutionary origins of this antiretroviral activity, its prevalence among the paralogs, and its ability to target retroviruses remain understudied. In agreement with previous studies, we found that four human SERINC paralogs inhibit nef-defective HIV-1, with SERINC2 being an exception. Here, we demonstrate that this lack of activity in human SERINC2 is associated with its post-whole-genome duplication (post-WGD) divergence, as evidenced by the ability of pre-WGD orthologs from Saccharomyces cerevisiae and flies and a post-WGD-proximate SERINC2 from coelacanths to inhibit the virus. Intriguingly, Nef is unable to counter coelacanth SERINC2, indicating that such activity was directed toward other retroviruses found in coelacanths (like foamy viruses). However, foamy virus-derived vectors are intrinsically resistant to the action of SERINC2, and we show that the foamy virus envelope confers this resistance by affecting its steady-state levels. Our study highlights an ancient origin of antiretroviral activity in SERINCs and a hitherto-unknown interaction with a foamy virus. IMPORTANCESERINC5 constitutes a critical barrier to the propagation of retroviruses, as highlighted by parallel emergence of anti-SERINC5 activities among distant retroviral lineages. Therefore, understanding the origin and evolution of these host factors will provide key information about virus-host relationships that can be exploited for future drug development. Here, we show that SERINC5-mediated nef-defective HIV-1 infection inhibition is evolutionarily conserved. SERINC2 from coelacanth restricts HIV-1, and it was functionally adapted to target foamy viruses. Our findings provide insights into the evolutionary origin of antiretroviral activity in the SERINC gene family and uncover the role of SERINCs in shaping the long-term conflicts between retroviruses and their hosts.

The genome sequence of Mesua ferrea and comparative demographic histories of forest trees.

Mesua ferrea (Family: Calophyllaceae) is a tropical forest plant used for timber, biofuel, and traditional medicine. Colloquially, it is known as Nagkesar (Cobra saffron) and is the state flower of Tripura (India). In this study, we perform the whole-genome assembly of Mesua ferrea using ~180X coverage paired-end Illumina data. Our de novo assembly is 614 Mega-base pair (Mbp), has an N50 of 392 Kilo-base pairs (Kbp), and an assembly quality comparable to other published Malpighiales genomes. Further, we collate the genomic datasets of 14 additional forest tree species to compare the temporal dynamics of Effective Population Size (Ne) and find evidence of a substantial bottleneck in all tropical forest plants during Mid-Pleistocene glaciations. The availability of this high-quality draft genome assembly will prove to be a useful resource for functional and comparative genomic studies.

Evidence for the loss of plasminogen receptor KT gene in chicken.

The loss of conserved genes has the potential to alter phenotypes drastically. Screening of vertebrate genomes for lineage-specific gene loss events has identified numerous natural knockouts associated with specific phenotypes. We provide evidence for the loss of a multi-exonic plasminogen receptor KT (PLGRKT) protein-encoding gene located on the Z chromosome in chicken. Exons 1 and 2 are entirely missing; remnants of exon 3 and a mostly intact exon 4 are identified in an assembly gap-free region in chicken with conserved synteny across species and verified using transcriptome and genome sequencing. PLGRKT gene disrupting changes are present in representative species from all five galliform families. In contrast to this, the presence of an intact transcriptionally active PLGRKT gene in species such as mallard, swan goose, and Anolis lizard suggests that gene loss occurred in the galliform lineage sometime between 68 and 80 Mya. The presence of galliform specific chicken repeat 1 (CR1) insertion at the erstwhile exon 2 of PLGRKT gene suggests repeat insertion-mediated loss. However, at least nine other independent PLGRKT coding frame disrupting changes in other bird species are supported by genome sequencing and indicate a role for relaxed purifying selection before CR1 insertion. The recurrent loss of a conserved gene with a role in the regulation of macrophage migration, efferocytosis, and blood coagulation is intriguing. Hence, we propose potential candidate genes that might be compensating the function of PLGRKT based on the presence of a C-terminal lysine residue, transmembrane domains, and gene expression patterns.

Loss of inner kinetochore genes is associated with the transition to an unconventional point centromere in budding yeast.

BACKGROUND: The genomic sequences of centromeres, as well as the set of proteins that recognize and interact with centromeres, are known to quickly diverge between lineages potentially contributing to post-zygotic reproductive isolation. However, the actual sequence of events and processes involved in the divergence of the kinetochore machinery is not known. The patterns of gene loss that occur during evolution concomitant with phenotypic changes have been used to understand the timing and order of molecular changes. METHODS: I screened the high-quality genomes of twenty budding yeast species for the presence of well-studied kinetochore genes. Based on the conserved gene order and complete genome assemblies, I identified gene loss events. Subsequently, I searched the intergenic regions to identify any un-annotated genes or gene remnants to obtain additional evidence of gene loss. RESULTS: My analysis identified the loss of four genes (NKP1, NKP2, CENPL/IML3 and CENPN/CHL4) of the inner kinetochore constitutive centromere-associated network (CCAN/also known as CTF19 complex in yeast) in both the Naumovozyma species for which genome assemblies are available. Surprisingly, this collective loss of four genes of the CCAN/CTF19 complex coincides with the emergence of unconventional centromeres in N. castellii and N. dairenensis. My study suggests a tentative link between the emergence of unconventional point centromeres and the turnover of kinetochore genes in budding yeast.

Hypoxia-induced changes in intragenic DNA methylation correlate with alternative splicing in breast cancer.

The tumor microenvironment is marked by gradients in the level of oxygen and nutrients, with oxygen levels reaching a minimum at the core of the tumor, a condition known as tumor hypoxia. Mediated by members of the HIF family of transcription factors, hypoxia leads to a more aggressive tumor phenotype by transactivation of several genes as well as reprogramming of pre-mRNA splicing. Intragenic DNA methylation, which is known to affect alternative splicing in cancer, could be one of several reasons behind the changes in splicing patterns under hypoxia. Here, we have tried to establish a correlation between intragenicDNA methylation and alternative usage of exons in tumor hypoxia. First, we have generated a customhypoxia signature consisting of 34 genes that are upregulated under hypoxia and are direct targets of HIF-1α. Using this gene expression signature, we have successfully stratified publicly available breast cancer patient samples into hypoxia positive and hypoxia negative groups followed by mining of differentially spliced isoforms between these groups. The Hypoxia Hallmark signature from MSigDB was also used independently to stratify the same tumor samples into hypoxic and normoxic.We found that 821 genes were showing differential splicing between samples stratified using a custom signature, whereas, 911 genes were showing differential splicing between samples stratified using the MSigDB signature. Finally, we performed multiple correlation tests between the methylation levels (ß) of microarray probes located within 1 kilo base pairs of isoform-specific exons using those exons' expression levels in the same patient samples in which the methylation level was recorded. We found that the expression level of one of the exons ofDHX32 and BICD2 significantly correlated with the methylation levels, and we were also able to predict patient survival (p-value: 0.02 for DHX32 and 0.0024 for BICD2). Our findings provide new insights into the potential functional role of intragenic DNA methylation in modulating alternative splicing during hypoxia.

Comparative analysis of corrected tiger genome provides clues to its neuronal evolution.

The availability of completed and draft genome assemblies of tiger, leopard, and other felids provides an opportunity to gain comparative insights on their unique evolutionary adaptations. However, genome-wide comparative analyses are susceptible to errors in genome sequences and thus require accurate genome assemblies for reliable evolutionary insights. In this study, while analyzing the tiger genome, we found almost one million erroneous substitutions in the coding and non-coding region of the genome affecting 4,472 genes, hence, biasing the current understanding of tiger evolution. Moreover, these errors produced several misleading observations in previous studies. Thus, to gain insights into the tiger evolution, we corrected the erroneous bases in the genome assembly and gene set of tiger using 'SeqBug' approach developed in this study. We sequenced the first Bengal tiger genome and transcriptome from India to validate these corrections. A comprehensive evolutionary analysis was performed using 10,920 orthologs from nine mammalian species including the corrected gene sets of tiger and leopard and using five different methods at three hierarchical levels, i.e. felids, Panthera, and tiger. The unique genetic changes in tiger revealed that the genes showing signatures of adaptation in tiger were enriched in development and neuronal functioning. Specifically, the genes belonging to the Notch signalling pathway, which is among the most conserved pathways involved in embryonic and neuronal development, were found to have significantly diverged in tiger in comparison to the other mammals. Our findings suggest the role of adaptive evolution in neuronal functions and development processes, which correlates well with the presence of exceptional traits such as sensory perception, strong neuro-muscular coordination, and hypercarnivorous behaviour in tiger.

Signatures of Relaxed Selection in the CYP8B1 Gene of Birds and Mammals.

The CYP8B1 gene is known to catalyse reactions that determine the ratio of primary bile salts and the loss of this gene has recently been linked to lack of cholic acid in the bile of naked-mole rats, elephants and manatees using forward genomics approaches. We screened the CYP8B1 gene sequence of more than 200 species and test for relaxation of selection along each terminal branch. The need for retaining a functional copy of the CYP8B1 gene is established by the presence of a conserved open reading frame across most species screened in this study. Interestingly, the dietary switch from bovid to cetacean species is accompanied by an exceptional ten amino acid extension at the C-terminal end through a single base frame-shift deletion. We also verify that the coding frame disrupting mutations previously reported in the elephant are correct, are shared by extinct Elephantimorpha species and coincide with the dietary switch to herbivory. Relaxation of selection in the CYP8B1 gene of the wombat (Vombatus ursinus) also corresponds to drastic change in diet. In summary, our forward genomics-based screen of bird and mammal species identifies recurrent changes in the selection landscape of the CYP8B1 gene concomitant with a change in dietary lipid content.

Epistatic mutations under divergent selection govern phenotypic variation in the crow hybrid zone.

The evolution of genetic barriers opposing interspecific gene flow is key to the origin of new species. Drawing from information on over 400 admixed genomes sourced from replicate transects across the European hybrid zone between all-black carrion crows and grey-coated hooded crows, we decipher the interplay between phenotypic divergence and selection at the molecular level. Over 68% of plumage variation was explained by epistasis between the gene NDP and a ~2.8-megabase region on chromosome 18 with suppressed recombination. Both pigmentation loci showed evidence for divergent selection resisting introgression. This study reveals how few, large-effect loci can govern prezygotic isolation and shield phenotypic divergence from gene flow.

Genome Sequence of Peacock Reveals the Peculiar Case of a Glittering Bird.

The unique ornamental features and extreme sexual traits of Peacock have always intrigued scientists and naturalists for centuries. However, the genomic basis of these phenotypes are yet unknown. Here, we report the first genome sequence and comparative analysis of peacock with the high quality genomes of chicken, turkey, duck, flycatcher and zebra finch. Genes involved in early developmental pathways including TGF-ß, BMP, and Wnt signaling, which have been shown to be involved in feather patterning, bone morphogenesis, and skeletal muscle development, revealed signs of adaptive evolution and provided useful clues on the phenotypes of peacock. Innate and adaptive immune genes involved in complement system and T-cell response also showed signs of adaptive evolution in peacock suggesting their possible role in building a robust immune system which is consistent with the predictions of the Hamilton-Zuk hypothesis. This study provides novel genomic and evolutionary insights into the molecular understanding toward the phenotypic evolution of Indian peacock.

A hypothetical new role for single-stranded DNA binding proteins in the immune system.

The breadth of the host range of single-stranded DNA (ssDNA) viruses is roughly comparable to the host range of double-stranded DNA viruses (dsDNA). Yet, general ssDNA sensing receptors that activate the immune system have not been unequivocally identified while numerous dsDNA sensing receptors are known. Here, we hypothesize that some of the Single-Stranded DNA Binding (SSB) proteins may act as receptors that detect single-stranded DNA from pathogens and activate the innate immune system. As the first test of our hypothesis, we checked whether human genes that are known to bind to ssDNA are potentially interferon-regulated. Out of the 102 human genes that are known to have ssDNA binding ability 23 genes show a more than two-fold increase in gene expression upon interferon treatment. Single-stranded DNA viruses are pathogens of not only animals but also of plants and protozoans. We used this information to further prioritize our candidate list to ssDNA binding genes that are common between the model plant Arabidopsis thaliana and humans. Based on these strategies, we shortlist several promising candidate genes including the HMGB1 gene which could act as a ssDNA sensor that activates the immune system. Agreeably though we cannot establish a definitive role for these genes as ssDNA sensors of the immune system as yet, our preliminary analysis suggests the potential existence of ssDNA binding protein-like receptors (SLR's) that are worth investigating further.