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Models of gene duplication and evolution of function. Indicated are various models for the evolution of function before and after gene duplication events. Gene dosage refers to maintenance of gene duplicates with the same function. Neofunctionalization refers to the acquisition of a new function and loss of the old function in one gene duplicate. Subfunctionalization refers to the segregation of two functions in different gene duplicates that was present in the ancestral gene. Multifunctionalization refers to acquisition of a new function in one gene copy, while retaining the original function. Escape from adaptive conflict refers to an ancestral gene with functions that are overlapping or sub-functional due to exclusion effects. These functions are optimized in respective gene duplicates after duplication. Adaptive radiation refers to ancestral genes that have pre-adapted functions, which allow the evolution of similar functions in gene duplicates. Permanent heterozygote refers to heterozygotes that have better fitness than homozygotes and where gene duplication leads to fixation of both alleles in paralogs. Multi-allelic diversification refers to the case where the highest number of heterozygous individuals in a population is advantageous. Gene duplications leads to many divergent genes coding for the same function.
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Ticks modulate their hosts' defense responses by secreting a biopharmacopiea of hundreds to thousands of proteins and bioactive chemicals into the feeding site (tick-host interface). These molecules and their functions evolved over millions of years as ticks adapted to blood-feeding, tick lineages diverged, and host-shifts occurred. The evolution o...
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... These two interfaces represent points of interactions between 83 tick genomes and the hemostatic and immune responses of their vertebrate hosts, 84 exerting a strong selective pressure on ticks and driving a diversification of the tick 85 genetic toolbox. 86 Gene duplication is believed to shape the major innovations in tick biology, and the 87 duplicate genes would facilitate the evolution of the metabolic potential of these 88 organisms (Mans et al. 2017). To understand the evolution of tick gene repertoires and 89 the importance of tick-specific duplications in particular, a comprehensive comparative 90 study of tick genomes is necessary, which is now possible thanks to the growing number 91 of available genome sequences both in ticks and in other Chelicerata. ...
... ; https://doi.org/10.1101/2024.02.29.581698 doi: bioRxiv preprint complete tick genome was published for Ixodes scapularis in 2016 (Gulia-Nuss et al. 95 2016), followed by the genomes of six other tick species, including Ixodes persulcatus 96 and five species belonging to a monophyletic group of non-Ixodes hard tick species, 97 known as the Metastriata (Jia et al. 2020). Two high quality genome sequences of I. 98 scapularis have been published recently (De et al. 2023;Nuss et al. 2023) that used the 99 newer generation of long-read high-throughput sequencing. 100 The purpose of our study was to improve our knowledge of tick genomics, especially in 101 the genus Ixodes which includes some of the most important vectors of tick-borne 102 disease in Europe, North America, and Asia. ...
... The most 142 notable change was the prediction of 500 entirely new gene models (supplementary 143 Table S2). The completeness (% of complete BUSCOs) of the four new gene catalogs 144 generated in this study fell within the range of recently sequenced tick genomes as 145 shown in Table 2. Completeness was lowest in I. pacificus (81%), and highest in I. 146 ricinus and I. hexagonus (about 91%), which is somewhat lower than the 98% observed 147 for the recently improved genome of I. scapularis (De et al. 2023). For I. pacificus, we 148 also note a relatively high percentage of "duplicated" genes in the BUSCO analysis, 149 suggesting that heterozygosity might have not been fully resolved and that our assembly 150 still contains duplicate alleles, which is supported by the higher heterozygosity estimate 151 for this genome (supplementary Fig. S1). ...
Ticks, hematophagous acari, pose a significant threat by transmitting various pathogens to their vertebrate hosts during feeding. Despite advances in tick genomics, high-quality genomes were lacking until recently, particularly in the genus Ixodes , which includes the main vectors of Lyme disease. Here, we present the complete genome sequences of four tick species, derived from a single female individual, with a particular focus on the European species Ixodes ricinus , achieving a chromosome-level assembly. Additionally, draft assemblies were generated for the three other Ixodes species, I. persulcatus, I. pacificus and I. hexagonus . The quality of the four genomes and extensive annotation of several important gene families have allowed us to study the evolution of gene repertoires at the level of the genus Ixodes and of the tick group. We have determined gene families that have undergone major amplifications during the evolution of ticks, while an expression atlas obtained for I. ricinus reveals striking patterns of specialization both between and within gene families. Notably, several gene family amplifications are associated with a proliferation of single-exon genes. The integration of our data with existing genomes establishes a solid framework for the study of gene evolution, improving our understanding of tick biology. In addition, our work lays the foundations for applied research and innovative control targeting these organisms.
... Molecular epidemiology has played a major role in tick research, including understanding genetic diversity, geographic distribution, co-evolution between ticks and their hosts and comparative genomics (Dickinson and Forman 2002;Boore 2006;Lara et al. 2015;Mans et al. 2017;Johnson 2019;Jia et al. 2020;Hodosi et al. 2022). Mitochondrial (mt) genomes of animals typically consist of a single circular chromosome, 14 kb ~ 16 kb in length (Wolstenholme 1992). ...
Ticks are blood-sucking ectoparasites with significant medical and veterinary importance, capable of transmitting bacteria, protozoa, fungi, and viruses that cause a variety of human and animal diseases worldwide. In the present study, we sequenced the complete mitochondrial (mt) genomes of five hard tick species and analyzed features of their gene contents and genome organizations. The complete mt genomes of Haemaphysalis verticalis, H. flava, H. longicornis, Rhipicephalus sanguineus and Hyalomma asiaticum were 14855 bp, 14689 bp, 14693 bp, 14715 bp and 14722 bp in size, respectively. Their gene contents and arrangements are the same as those of most species of metastriate Ixodida, but distinct from species of genus Ixodes. Phylogenetic analyses using concatenated amino acid sequences of 13 protein-coding genes with two different computational algorithms (Bayesian inference and maximum likelihood) revealed the monophylies of the genera Rhipicephalus, Ixodes and Amblyomma, however, rejected the monophyly of the genus Haemaphysalis. To our knowledge, this is the first report of the complete mt genome of H. verticalis. These datasets provide useful mtDNA markers for further studies of the identification and classification of hard ticks.
... The sequencing depth of NGS also allowed unprecedented insight into differential expression leading to hypothesis on sialome switching to evade host immune responses [81,82], and a deep insight into the fluctuation of protein expression over the course of feeding that revealed a complexity not imagined before [82]. Hypotheses on either host-parasite arms races or neutral evolution to explain salivary gland protein diversity have also been advanced [81,83]. In addition, our knowledge of functions relevant at the tick-feeding site has also expanded over the past 20 years [84], and potential roles for miRNA, long noncoding RNA, and exosomes have been identified in feeding [85][86][87]. ...
... The developments above may be considered paradigm shifting, and they hold the promise that we may have a comprehensive understanding of tick-host interactions in the future. It will also allow insight into the evolution of protein function over lineages and time [2,83]. This will enable us to have deeper insights into how ticks evolved a blood-feeding lifestyle. ...
... This will enable us to have deeper insights into how ticks evolved a blood-feeding lifestyle. Current issues revolve around whether the current technologies allow us to have a comprehensive insight into the complexity of the sialome (transcriptome and proteome) and whether we are able to fully describe the sialome and its myriad functions, whether sialome switching is a true phenomenon, whether host arms races or neutral evolution can explain protein diversity, and whether nonprotein-based molecules such as miRNA and long-noncoding RNA play a significant role in tick-feeding [80,83,84]. ...
The study of tick evolution may be classified into disciplines such as taxonomy and systematics, biogeography, evolution and development (evo-devo), ecology, and hematophagy. These disciplines overlap and impact each other to various extents. Advances in one field may lead to paradigm shifts in our understanding of tick evolution not apparent to other fields. The current study considers paradigm shifts that occurred, are in the process, or may occur in future for the disciplines that study tick evolution. Some disciplines have undergone significant changes, while others may still be developing their own paradigms. Integration of these various disciplines is essential to come to a holistic view of tick evolution; however, maturation of paradigms may be necessary before this vision can be attained.
... Based on their physiological importance, the potential anti-tick vaccine efficacy of these immunogenic proteins against multiple ticks has been determined [7][8][9][10][11][12][13], and Rm05Uy was suggested as a candidate antigen for inclusion in the future anti-tick vaccine development [15]. Ticks have undergone different evolutionary processes marked by morphological and genetic variations [16]. In particular, sequence polymorphisms in the Bm86, ATAQ, and cathepsin L-like cysteine proteinase genes in Rhipicephalus microplus strains have been reported in different geographical locations [17][18][19][20][21]. ...
Rhipicephalus microplus tick highly affects the veterinary sector throughout the world. Different tick control methods have been adopted, and the identification of tick-derived highly immuno-genic sequences for the development of an anti-tick vaccine has emerged as a successful alter-nate. This study aimed to characterize immunogenic sequences from R. microplus ticks prevalent in Pakistan. Ticks collected in the field were morphologically identified and subjected to DNA and RNA extraction. Ticks were molecularly identified based on the partial mitochondrial cyto-chrome C oxidase subunit (cox) sequence and screened for piroplasms (Theileria/Babesia spp.), Rick-ettsia spp., and Anaplasma spp. PCR-based pathogens-free R. microplus-derived cDNA was used for the amplification of full-length cysteine protease inhibitor (cystatin 2b), cathepsin L-like cysteine proteinase (cathepsin-L), glutathione S-transferase (GST), ferritin 1, 60S acidic ribosomal protein (P0), aquaporin 2, ATAQ, and R. microplus 05 antigen (Rm05Uy) coding sequences. The cox se-quence revealed 100% identity with the nucleotide sequences of Pakistan's formerly reported R. microplus, and full-length immunogenic sequences revealed maximum identities to the most similar sequences reported from India, China, Cuba, USA, Brazil, Egypt, Mexico, Israel, and Uruguay. Low nonsynonymous polymorphisms were observed in ATAQ (1.5%), cathepsin-L (0.6%), and aquaporin 2 (0.4%) sequences compared to the homologous sequences from Mexico, India, and the USA, respectively. Based on the cox sequence, R. microplus was phylogenetically assembled in clade C, which includes R. microplus from Pakistan, Myanmar, Malaysia, Thailand, Bangladesh, and India. In the phylogenetic trees, the cystatin 2b, cathepsin-L, ferritin 1, and aq-uaporin 2 sequences were clustered with the most similar available sequences of R. microplus, P0 with R. microplus, R. sanguineus and R. haemaphysaloides, and GST, ATAQ, and Rm05Uy with R. mi-croplus and R. annulatus. This is the first report on the molecular characterization of clade C R. microplus-derived immunogenic sequences.
... Tick-induced paralysis is the most widespread and dominant form of tick toxicoses is caused by Amblyomma aculatum on the Mexican Pacific Coast [33]. Australian paralysis is caused by tick Ixodes holocyclus [34]. ...
The present review article explains different zoonotic diseases transmitted by various species of ticks. This article emphasizes various animal hosts, transmission and prevalence of various zoonotic diseases caused by a virus, bacteria, protozoans in different eco-climatic regions of the world. This article also explains various diagnostic methods applied for the detection of disease pathogens, treatment methods and prophylactic measures. It recommends tick saliva antigen-based oral vaccines and antibiotics as treatment methods. It also suggests use of various bait formulations and cultural control methods for deterring ticks from blood feeding. This article signifies the need of pesticides for control of ticks and tick-borne diseases.
... For successful blood uptake, tick's mouthparts penetrate through the host skin, create a blood pool and the feeding process lasting up to several days, is boosted and ensured by tick salivary bioactive molecules. Tick saliva is a very complex fluid containing an incredible amount of diverse biologically active molecules that not only ensure the feeding process by overcoming host haemostasis and immune defences (Kotál et al. 2015;Mans et al. 2017;Šimo et al. 2017;Nuttall 2018;Wikel 2018;Štibrániová et al. 2019) but also support transmission and local settlement of many tick-borne pathogens (TBP) in the immunomodulated feeding site (Nuttall andLabuda 2004, 2008;Kazimírová and Štibrániová 2013;Wikel 2013;Kazimírová et al. 2017;Šimo et al. 2017;Nuttall 2018). Indirect promotion of TBP transmission via interference of tick saliva substances with host immunity has been named saliva-assisted transmission (SAT) (Nuttall and Labuda 2008). ...
Ticks, unique hematophagous arthropods and very effective vectors of a diverse spectrum of pathogens, possess an astounding array of salivary molecules that ensure their unnoticed and prolonged attachment to the host skin by counteracting host defences, including immune cells. Natural killer (NK) cells, belonging to the main cellular components of innate immunity, are specialized lymphocytes with the ability to recognize and eliminate pathogen-infected cells and tumour cells. Previously we showed that salivary gland extracts (SGE) derived from adult Dermacentor reticulatus ticks suppressed cytotoxic activity of human NK cells. The decrease was observed with SGE from both partially fed female and male ticks as well as from partially fed female Amblyomma variegatum and Haemaphysalis inermis. In this study, we determined that SGE from both sexes of adult D. reticulatus and A. variegatum and from females of Haemaphysalis concina inhibited cytotoxic activity of mouse NK cells in vivo stimulated with polyinosinic-polycytidylic acid (poly I:C). The decrease effect was observed with SGE from partially fed ticks, but no significant inhibition was determined with SGE from unfed ticks. On the other hand, no significant decrease of NK activity was detected after treatment with SGE from partially fed adult Ixodes ricinus, H. inermis, Rhipicephalus appendiculatus and Rhipicephalus pulchellus. According to the results from proteomic approaches we assume that the anti-NK activity molecule(s) is (are) very basic protein(s) with a molecular weight of approximately 30 kDa.
... It remains to be determined whether such evasinlike proteins are capable of binding chemokines. If neutral evolution and genetic drift are the major reasons for diversity in salivary gland proteins (Mans et al., 2017), many evasin-like proteins may be sub-or non-functional or have new (nonevasin) functionsa hypothesis that needs to be tested. Taken together these results suggest that class B evasins, which are identified in four Metastriate genera and two Prostriate species, arose prior to the divergence of Prostriate and Metastriate lineages, which occurred~200-249 MYA (Mans et al., 2012;Jia et al., 2020), and likely functioned to neutralize CXC-chemokines and support blood feeding. ...
Chemokines are structurally related proteins that activate leucocyte migration in response to injury or infection. Tick saliva contains chemokine-binding proteins or evasins which likely neutralize host chemokine function and inflammation. Biochemical characterisation of 50 evasins from Ixodes, Amblyomma and Rhipicephalus shows that they fall into two functional classes, A and B, with exclusive binding to either CC- or CXC- chemokines, respectively. Class A evasins, EVA1 and EVA4 have a four-disulfide-bonded core, whereas the class B evasin EVA3 has a three-disulfide-bonded “knottin” structure. All 29 class B evasins have six cysteine residues conserved with EVA3, arrangement of which defines a Cys6-motif. Nineteen of 21 class A evasins have eight cysteine residues conserved with EVA1/EVA4, the arrangement of which defines a Cys8-motif. Two class A evasins from Ixodes (IRI01, IHO01) have less than eight cysteines. Many evasin-like proteins have been identified in tick salivary transcriptomes, but their phylogenetic relationship with respect to biochemically characterized evasins is not clear. Here, using BLAST searches of tick transcriptomes with biochemically characterized evasins, we identify 292 class A and 157 class B evasins and evasin-like proteins from Prostriate (Ixodes), and Metastriate (Amblyomma, Dermacentor, Hyalomma, Rhipicephalus) ticks. Phylogenetic analysis shows that class A evasins/evasin-like proteins segregate into two classes, A1 and A2. Class A1 members are exclusive to Metastriate ticks and typically have a Cys8-motif and include EVA1 and EVA4. Class A2 members are exclusive to Prostriate ticks, lack the Cys8-motif, and include IHO01 and IRI01. Class B evasins/evasin-like proteins are present in both Prostriate and Metastriate lineages, typically have a Cys6-motif, and include EVA3. Most evasins/evasin-like proteins in Metastriate ticks belong to class A1, whereas in Prostriate species they are predominantly class B. In keeping with this, the majority of biochemically characterized Metastriate evasins bind CC-chemokines, whereas the majority of Prostriate evasins bind CXC-chemokines. While the origin of the structurally dissimilar classes A1 and A2 is yet unresolved, these results suggest that class B evasin-like proteins arose before the divergence of Prostriate and Metastriate lineages and likely functioned to neutralize CXC-chemokines and support blood feeding.
... Based on their properties, TSGPs can be divided in large multi-gene families that have distinct functionalities, as reviewed before 30 . These multi-gene families are thought to be the result of gene duplication early in evolution 31 . ...
Ixodes ricinus is the vector for Borrelia afzelii, the predominant cause of Lyme borreliosis in Europe, whereas Ixodes scapularis is the vector for Borrelia burgdorferi in the USA. Transcription of several I. scapularis genes changes in the presence of B. burgdorferi and contributes to successful infection. To what extend B. afzelii influences gene expression in I. ricinus salivary glands is largely unknown. Therefore, we measured expression of uninfected vs. infected tick salivary gland genes during tick feeding using Massive Analysis of cDNA Ends (MACE) and RNAseq, quantifying 26.179 unique transcripts. While tick feeding was the main differentiator, B. afzelii infection significantly affected expression of hundreds of transcripts, including 465 transcripts after 24 h of tick feeding. Validation of the top-20 B. afzelii-upregulated transcripts at 24 h of tick feeding in ten biological genetic distinct replicates showed that expression varied extensively. Three transcripts could be validated, a basic tail protein, a lipocalin and an ixodegrin, and might be involved in B. afzelii transmission. However, vaccination with recombinant forms of these proteins only marginally altered B. afzelii infection in I. ricinus-challenged mice for one of the proteins. Collectively, our data show that identification of tick salivary genes upregulated in the presence of pathogens could serve to identify potential pathogen-blocking vaccine candidates.
... These proteins may not be functionally annotated due to cloning or sequencing errors or shifted reading frames 33,62 . Nevertheless, tick salivary proteins are under intense selection pressure through co-evolution with different hosts 14,17,63 . Genes without known function can be expressed at potentially biologically meaningful levels, and the evaluation of these genes could provide missing links in our understanding of tick feeding. ...
‘Omics’ technologies have facilitated the identification of hundreds to thousands of tick molecules that mediate tick feeding and play a role in the transmission of tick‐borne diseases. Deep sequencing methodologies have played a key role in this knowledge accumulation, profoundly facilitating the study of the biology of disease vectors lacking reference genomes. For example, the nucleotide sequences of the entire set of tick salivary effectors, the so‐called tick ‘sialome’, now contain at least one order of magnitude more transcript sequences compared to similar projects based on Sanger sequencing. Tick feeding is a complex and dynamic process, and while the dynamic ‘sialome’ is thought to mediate tick feeding success, exactly how transcriptome dynamics relate to tick‐host‐pathogen interactions is still largely unknown. The identification and, importantly, the functional analysis of the tick ‘sialome’ is expected to shed light on this ‘black box’. This information will be crucial for developing strategies to block pathogen transmission, not only for anti‐tick vaccine development but also the discovery and development of new, pharmacologically active compounds for human diseases.
... As coverage is increased for other species, novel genes coding for products of the 5 ′ -nucleotidase/Apyrase should appear. The phylogram indicates the existence of at least seven genes coding for secreted apyrases from I. ricinus, based on the branches having 100% bootstrap support; the amino acid divergence of the secreted proteins is larger than that of the housekeeping, GPI anchored sequences, indicating faster evolution of the genes coding for secreted salivary genes; this was either caused by neutral evolution of these genes when compared to a purifying evolution scenario of the housekeeping genes, or due to positive selection pressure on the genes coding for secreted enzymes, driven by the immune pressure of their hosts (Mans et al., 2017). Submission of the apyrase coding enzymes to the FUBAR analysis (Murrell et al., 2013) indicated no sites under positive selection. ...
... The TSFam database, and its associated hyperlinked spreadsheets of tick salivary proteins and associated nucleotide sequences, helps the annotation of tick salivary secreted proteins, as well as the retrieval of these sequences for phylogenetic studies. It has been reported that the genes coding for salivary proteins of blood sucking arthropods show high evolutionary rates; either due to the relaxed constraint of the genes allowing for less negative selection pressure, or for the more rare occurrence of positive selection Schroeder et al., 2007;Decrem et al., 2008;Dai et al., 2012;Arca et al., 2014;Mans et al., 2017). The phylogenetic analysis, derived from the alignment of tick salivary coding sequences from the lipocalin, metalloprotease, cystatin, apyrase, DAP36, and subolesin families (Supplemental Figures 1-6 and Table 3), indicate a high number of recombination breakpoints on the genes coding for lipocalins (11 sites) and DAP36 (6 sites); three recombination breakpoint sites for the apyrase and metalloproteases; and one recombination breakpoint on the genes coding for the cystatins and subolesin. ...
Tick saliva contains a complex mixture of peptides and non-peptides that counteract their hosts' hemostasis, immunity, and tissue-repair reactions. Recent transcriptomic studies have revealed over one thousand different transcripts coding for secreted polypeptides in a single tick species. Not only do these gene products belong to many expanded families, such as the lipocalins, metalloproteases, Antigen-5, cystatins, and apyrases, but also families that are found exclusively in ticks, such as the evasins, Isac, DAP36, and many others. Phylogenetic analysis of the deduced protein sequences indicate that the salivary genes exhibit an increased rate of evolution due to a lower evolutionary constraint and/or positive selection, allowing for a large diversity of tick salivary proteins. Thus, for each new tick species that has its salivary transcriptome sequenced and assembled, a formidable task of annotation of these transcripts awaits. Currently, as of November 2019, there are over 287 thousand coding sequences deposited at the National Center for Biotechnology Information (NCBI) that are derived from tick salivary gland mRNA. Here, from these 287 thousand sequences we identified 45,264 potential secretory proteins which possess a signal peptide and no transmembrane domains on the mature peptide. By using the psiblast tools, position-specific matrices were constructed and assembled into the TickSialoFam (TSF) database. The TSF is a rpsblastable database that can help with the annotation of tick sialotranscriptomes. The TSA database identified 136 tick salivary secreted protein families, as well as 80 families of endosomal-related products, mostly having a protein modification function. As the number of sequences increases, and new annotation details become available, new releases of the TSF database may become available.
