Database Homology Research Articles

Fast, sensitive detection of protein homologs using deep dense retrieval.

The identification of protein homologs in large databases using conventional methods, such as protein sequence comparison, often misses remote homologs. Here, we offer an ultrafast, highly sensitive method, dense homolog retriever (DHR), for detecting homologs on the basis of a protein language model and dense retrieval techniques. Its dual-encoder architecture generates different embeddings for the same protein sequence and easily locates homologs by comparing these representations. Its alignment-free nature improves speed and the protein language model incorporates rich evolutionary and structural information within DHR embeddings. DHR achieves a >10% increase in sensitivity compared to previous methods and a >56% increase in sensitivity at the superfamily level for samples that are challenging to identify using alignment-based approaches. It is up to 22 times faster than traditional methods such as PSI-BLAST and DIAMOND and up to 28,700 times faster than HMMER. The new remote homologs exclusively found by DHR are useful for revealing connections between well-characterized proteins and improving our knowledge of protein evolution, structure and function.

Identification of a novel protein Hq023 of the hard tick Haemaphysalis qinghaiensis and preliminary evaluation of its analgesic effect in mice model

Tick saliva contains a range of critical biological molecules which could inhibit host defenses and guarantee their food supply. Hq023, a novel cDNA sequence, was cloned from a cDNA library constructed from salivary glands of partially-engorged Haemaphysalis qinghaiensis. Hq023 has an open reading frame (ORF) of 408 bp coding a protein containing 135 amino acid residues with a molecular mass of 15 kDa. Database homology showed that Hq023 protein was structurally similar to a natural toxin U33-theraphotoxin-Cg1c from the Chinese tarantula Chilobrachys guangxiensis. A recombinant protein was expressed with the novel cDNA in a prokaryotic system and its analgesic effect was evaluated in mice model. Both tail immersion and hot-plate tests uncovered an antinociceptive activity, while in the acetic acid-induced writhing test this effect was not observed. These results indicated that the novel recombinant protein Hq023 (rHq023) probably possessed a central antinociceptive activity. Finding of the novel protein might pave a new avenue for the development of tick-derived analgesics.

Genome sequencing and analysis of penicillin V producing Penicillium rubens strain BIONCL P45 isolated from India.

A filamentous fungus Penicillium rubens is widely recognized for producing industrially important antibiotic, penicillin at industrial scale. To better comprehend, the genetic blueprint of the wild-type P. rubens was isolated from India to identify the genetic/biosynthetic pathways for phenoxymethylpenicillin (penicillin V, PenV) and other secondary metabolites. Genomic DNA (gDNA) was isolated, and library was prepared as per Illumina platform. Whole genome sequencing (WGS) was performed according to Illumina NovoSeq platform. Further, SOAPdenovo was used to assemble the short reads validated by Bowtie-2 and SAMtools packages. Glimmer and GeneMark were used to dig out total genes in genome. Functional annotation of predicted proteins was performed by NCBI non-redundant (NR), UniProt, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) databases. Moreover, secretome analysis was performed by SignalP 4.1 and TargetP v1.1 and carbohydrate-active enzymes (CAZymes) and protease families by CAZy database. Comparative genome analysis was performed by Mauve 2.4.0. software to find genomic correlation between P. rubens BIONCL P45 and Penicillium chrysogenum Wisconsin 54-1255; also phylogeny was prepared with known penicillin producing strains by ParSNP tool. Penicillium rubens BIONCL P45 strain was isolated from India and is producing excess PenV. The 31.09Mb genome was assembled with 95.6% coverage of the reference genome P. chrysogenum Wis 54-1255 with 10687 protein coding genes, 3502 genes had homologs in NR, UniProt, KEGG, and GO databases. Additionally, 358 CAZymes and 911 transporter coding genes were found in genome. Genome contains complete pathways for penicillin, homogentisate pathway of phenyl acetic acid (PAA) catabolism, Andrastin A, Sorbicillin, Roquefortine C, and Meleagrin. Comparative genome analysis of BIONCL P45 and Wis 54-1255 revealed 99.89% coverage with 2952 common KEGG orthologous protein-coding genes. Phylogenetic analysis revealed that BIONCL P45 was clustered with Fleming's original isolate P. rubens IMI 15378. This genome can be a helpful resource for further research in developing fermentation processes and strain engineering approaches for high titer penicillin production.

Isolation and characterization of a novel lytic Parabacteroides distasonis bacteriophage φPDS1 from the human gut

ABSTRACT The human gut microbiome plays a significant role in health and disease. The viral component (virome) is predominantly composed of bacteriophages (phages) and has received significantly less attention in comparison to the bacteriome. This knowledge gap is largely due to challenges associated with the isolation and characterization of novel gut phages, and bioinformatic hurdles such as the lack of a universal phage marker gene and the absence of sufficient numbers of homologs in viral databases. Here, we describe the isolation from human feces of a novel lytic phage with siphovirus morphology, φPDS1, infecting Parabacteroides distasonis APCS2/PD, and classified within a newly proposed Sagittacolavirus genus. In silico and biological characterization of this phage is presented in this study. Key to the isolation of φPDS1 was the antibiotic-driven selective enrichment of the bacterial host in a fecal fermenter. Despite producing plaques and lacking genes associated with lysogeny, φPDS1 demonstrates the ability to coexist in liquid culture for multiple days without affecting the abundance of its host. Multiple studies have shown that changes in Parabacteroides distasonis abundance can be linked to various disease states, rendering this novel phage-host pair and their interactions of particular interest.

UhpTE350Q mutation along with the presence of fosA6/5 genes in the genome probably contributes to inherent fosfomycin resistance of Klebsiella pneumoniae

To investigate the molecular mechanism underlying inherent fosfomycin resistance of Klebsiella pneumoniae (K. pneumoniae). The draft genomic sequences of 14 clinical hypervirulent/hypermucoviscous K. pneumoniae (HvKP/ HmKP) isolates were obtained using the next-generation sequencing technology. The genomic sequences were analyzed using the Resistance Gene Identifier (RGI) software for predicting the resistome based on homology and SNP models in the Comprehensive Antibiotic Resistance Database (CARD) and for identification of the presence of phosphomycin resistancerelated genes uhpt and fosA and their mutations in the bacterial genomes. The results were verified by analyzing a total of 521 full-length genomic sequences of K. pneumonia strains obtained from GenBank. All the 14 clinical isolates of HvKP/ HmKP carried hexose phosphate transporter (UhpT) gene mutation, in which the glutamic acid was mutated to glutamine at 350aa (UhpTE350Q mutation); the presence of fosA6 gene was detected in 12 (85.71%) of the isolates and fosA5 gene was detected in the other 2 (14.29%) isolates. Analysis of the genomic sequences of 521 K. pneumonia strains from GenBank showed that 508 (97.50%) strains carried UhpTE350Q mutation, 439 (84.26%) strains harbored fosA6, and 80 (15.36%) strains harbored fosA5; 507 (97.31%) strains were found to have both UhpTE350Q mutation and fosA6/5 genes in the genome. Only 12 (2.30%) strains carried fosA6/5 genes without UhpTE350Q mutation; 1 (0.19%) strain had only UhpTE350Q mutation without fosA6/5 genes, and another strain contained neither UhpTE350Q mutation nor fosA6/5 genes. UhpTE350Q mutation with the presence of fosA6/5 genes are ubiquitous in K. pneumonia genomes, indicating a possible intrinsic mechanism of fosfomycin resistance in the bacterium to limit the use of fosfomycin against infections caused by K. pneumoniae, especially the multi-resistant HvKP/HmKP strains.

The Clostridium-infecting filamentous phage CAK1 genome analysis allows to define a new potential clade of Tubulavirales.

What we know about Tubulavirales, i.e. filamentous phages, essentially comes from Gram-negative-infecting Inoviridae. However, metagenomics recently suggests filamentous phages are much more widespread and diverse. Here, we report the complete sequence and functional annotation of CAK1, a 6.6kb filamentous phage that was shown to chronically infect Clostridium beijerinckii 30 years ago and only represents the second filamentous phage cultivated on a Gram-positive bacterium. CAK1 has a typical filamentous phage modular genome with no homologs in databases and we were interested to compare it with a pig gut filamentous phage metagenomics dataset that we previously assembled and for which many filamentous phages were predicted to infect Clostridium species by bioinformatics means. CAK1 is distantly related to nine of these sequences, two of which having been predicted as Clostridium-associated. In itself, this small cluster of CAK1-connected sequences sheds light on the diversity of filamentous phages that putatively infect Clostridium species, and probably many other Gram-positive genera.

The p.Pro2232Leu variant in the ChEL domain of thyroglobulin gene causes intracellular transport disorder and congenital hypothyroidism.

Thyroglobulin (TG), the predominant glycoprotein of the thyroid gland, functions as matrix protein in thyroid hormonegenesis. TG deficiency results in thyroid dyshormonogenesis. These variants produce a heterogeneous spectrum of congenital goitre, with an autosomal recessive mode of inheritance. The purpose of this study was to identify and functionally characterize new variants in the TG gene in order to increase the understanding of the molecular mechanisms responsible for thyroid dyshormonogenesis. A total of four patients from two non-consanguineous families with marked alteration of TG synthesis were studied. The two families were previously analysed in our laboratory, only one deleterious allele, in each one, was detected after sequencing the TG gene (c.2359 C > T [p.Arg787*], c.5560 G > T [p.Glu1854*]). These findings were confirmed in the present studies by Next-Generation Sequencing. The single nucleotide coding variants of the TG gene were then analyzed to predict the possible variant causing the disease. The p.Pro2232Leu (c.6695 C > T), identified in both families, showing a low frequency population in gnomAD v2.1.1 database and protein homology, amino acid prediction, and 3D modeling analysis predict a potential pathogenic effect of this variant. We also transiently express p.Pro2232Leu in a full-length rat TG cDNA clone and confirmed that this point variant was sufficient to cause intracellular retention of mutant TG in HEK293T cells. Consequently, each family carried a compound heterozygous for p.Arg787*/p.Pro2232Leu or p.Glu1854*/p.Pro2232Leu variants. In conclusion, our results confirm the pathophysiological importance of altered TG folding as a consequence of missense variants located in the ChEL domain of TG.

Chromosome-level genome assembly of the bar-headed goose (Anser indicus)

Bar-headed geese (Anser indicus) are adaptable to plateau environments. In this study, we sequenced and assembled a high-quality chromosome-level genome of the bar-headed goose using PacBio long reads and Hi-C technique, and generated 115.73 Gb of Illumina short-reads and 95.89 Gb of PacBio long-reads. The assembled bar-headed goose genome, with a contig N50 of 5.734 Mb and a scaffold N50 of 65.77 Mb, is 1.129 Gb in length and includes 33 chromosomes and 451 fragments. BUSCO assessment yielded a completeness score of 94.4%. In total, 15,376 protein-coding genes were predicted, of which 94.95% had homologs in protein databases. We identified 78 positively selected genes (PSGs) in the bar-headed goose genome, which were mainly enriched in calcium ion and ATP-binding. This bar-headed goose genome will be an important resource for increasing our understanding regarding the genetic basis of adaptation to life at a high altitude.

Proteomic and Transcriptomic Analyses in the Slipper Snail Crepidula fornicata Uncover Shell Matrix Genes Expressed During Adult and Larval Biomineralization.

SynopsisThe gastropod shell is a composite composed of minerals and shell matrix proteins (SMPs). SMPs have been identified by proteomics in many molluscs, but few have been studied in detail. Open questions include (1) what gene regulatory networks regulate SMP expression, (2) what roles individual SMPs play in biomineralization, and (3) how the complement of SMPs changes over development. These questions are best addressed in a species in which gene perturbation studies are available; one such species is the slipper snail, Crepidula fornicata. Here, SEM and pXRD analysis demonstrated that the adult shell of C. fornicata exhibits crossed lamellar microstructure and is composed of aragonite. Using high-throughput proteomics we identified 185 SMPs occluded within the adult shell. Over half of the proteins in the shell proteome have known biomineralization domains, while at least 10% have no homologs in public databases. Differential gene expression analysis identified 20 SMP genes that are up-regulated in the shell-producing mantle tissue. Over half of these 20 SMPs are expressed during development with two, CfSMP1 and CfSMP2, expressed exclusively in the shell gland. Together, the description of the shell microstructure and a list of SMPs now sets the stage for studying the consequences of SMP gene knockdowns in molluscs.

Improvement of eukaryotic protein predictions from soil metagenomes

During the last decades, metagenomics has highlighted the diversity of microorganisms from environmental or host-associated samples. Most metagenomics public repositories use annotation pipelines tailored for prokaryotes regardless of the taxonomic origin of contigs. Consequently, eukaryotic contigs with intrinsically different gene features, are not optimally annotated. Using a bioinformatics pipeline, we have filtered 7.9 billion contigs from 6,872 soil metagenomes in the JGI’s IMG/M database to identify eukaryotic contigs. We have re-annotated genes using eukaryote-tailored methods, yielding 8 million eukaryotic proteins and over 300,000 orphan proteins lacking homology in public databases. Comparing the gene predictions we made with initial JGI ones on the same contigs, we confirmed our pipeline improves eukaryotic proteins completeness and contiguity in soil metagenomes. The improved quality of eukaryotic proteins combined with a more comprehensive assignment method yielded more reliable taxonomic annotation. This dataset of eukaryotic soil proteins with improved completeness, quality and taxonomic annotation reliability is of interest for any scientist aiming at studying the composition, biological functions and gene flux in soil communities involving eukaryotes.

MrParse: finding homologues in the PDB and the EBI AlphaFold database for molecular replacement and more.

Crystallographers have an array of search-model options for structure solution by molecular replacement (MR). The well established options of homologous experimental structures and regular secondary-structure elements or motifs are increasingly supplemented by computational modelling. Such modelling may becarried out locally or may use pre-calculated predictions retrieved from databases such as the EBI AlphaFold database. MrParse is a new pipeline to help to streamline the decision process in MR by consolidating bioinformatic predictions in one place. When reflection data are provided, MrParse can rank any experimental homologues found using eLLG, which indicates the likelihood that a given search model will work in MR. Inbuilt displays of predicted secondary structure, coiled-coil and transmembrane regions further inform the choice of MR protocol. MrParse can also identify and rank homologues in the EBI AlphaFold database, a function that will also interest other structural biologists and bioinformaticians.

"Yaraviridae": a proposed new family of viruses infecting Acanthamoeba castellanii.

Here, we propose the creation of the family "Yaraviridae", a new taxon to classify a virus infecting Acanthamoeba castellanii cells. Recently, we described the discovery of a new virus infecting free-living amoebae, yaravirus, which has features that strongly differ from those of all other viruses of amoebae described to date. Yaravirus particles are about 80 nm in diameter and have a dsDNA genome of ~45 kbp containing 74 ORFs, most of which (>90%) have no homologs in current databases. Together, these data support the creation of a new species ("Yaravirus brasiliense"), a new viral genus (here proposed as "Yaravirus"), and a new viral family (here proposed as "Yaraviridae") to classify yaravirus and other related viruses that may be described in the future. All of them are to be included into the existing realm Varidnaviria and the kingdom Bamfordvirae, due to the presence of a major capsid protein containing a double jelly-roll fold.

Genomic Analysis of the First European Bacteriophages with Depolymerase Activity and Biocontrol Efficacy against the Phytopathogen Ralstonia solanacearum.

Ralstonia solanacearum is the causative agent of bacterial wilt, one of the most destructive plant diseases. While chemical control has an environmental impact, biological control strategies can allow sustainable agrosystems. Three lytic bacteriophages (phages) of R. solanacearum with biocontrol capacity in environmental water and plants were isolated from river water in Europe but not fully analysed, their genomic characterization being fundamental to understand their biology. In this work, the phage genomes were sequenced and subjected to bioinformatic analysis. The morphology was also observed by electron microscopy. Phylogenetic analyses were performed with a selection of phages able to infect R. solanacearum and the closely related phytopathogenic species R. pseudosolanacearum. The results indicated that the genomes of vRsoP-WF2, vRsoP-WM2 and vRsoP-WR2 range from 40,688 to 41,158 bp with almost 59% GC-contents, 52 ORFs in vRsoP-WF2 and vRsoP-WM2, and 53 in vRsoP-WR2 but, with only 22 or 23 predicted proteins with functional homologs in databases. Among them, two lysins and one exopolysaccharide (EPS) depolymerase, this type of depolymerase being identified in R. solanacearum phages for the first time. These three European phages belong to the same novel species within the Gyeongsanvirus, Autographiviridae family (formerly Podoviridae). These genomic data will contribute to a better understanding of the abilities of these phages to damage host cells and, consequently, to an improvement in the biological control of R. solanacearum.

Poorly Conserved P15 Proteins of Cileviruses Retain Elements of Common Ancestry and Putative Functionality: A Theoretical Assessment on the Evolution of Cilevirus Genomes.

The genus Cilevirus groups enveloped single-stranded (+) RNA virus members of the family Kitaviridae, order Martellivirales. Proteins P15, scarcely conserved polypeptides encoded by cileviruses, have no apparent homologs in public databases. Accordingly, the open reading frames (ORFs) p15, located at the 5′-end of the viral RNA2 molecules, are considered orphan genes (ORFans). In this study, we have delved into ORFs p15 and the relatively poorly understood biochemical properties of the proteins P15 to posit their importance for viruses across the genus and theorize on their origin. We detected that the ORFs p15 are under purifying selection and that, in some viral strains, the use of synonymous codons is biased, which might be a sign of adaptation to their plant hosts. Despite the high amino acid sequence divergence, proteins P15 show the conserved motif [FY]-L-x(3)-[FL]-H-x-x-[LIV]-S-C-x-C-x(2)-C-x-G-x-C, which occurs exclusively in members of this protein family. Proteins P15 also show a common predicted 3D structure that resembles the helical scaffold of the protein ORF49 encoded by radinoviruses and the phosphoprotein C-terminal domain of mononegavirids. Based on the 3D structural similarities of P15, we suggest elements of common ancestry, conserved functionality, and relevant amino acid residues. We conclude by postulating a plausible evolutionary trajectory of ORFans p15 and the 5′-end of the RNA2 of cileviruses considering both protein fold superpositions and comparative genomic analyses with the closest kitaviruses, negeviruses, nege/kita-like viruses, and unrelated viruses that share the ecological niches of cileviruses.

In Vitro Oxidative Crosslinking of Recombinant Barnacle Cyprid Cement Gland Proteins

Barnacle adhesion is a focus for fouling-control technologies as well as the development of bioinspired adhesives, although the mechanisms remain very poorly understood. The barnacle cypris larva is responsible for surface colonisation. Cyprids release cement from paired glands that contain proteins, carbohydrates and lipids, although further compositional details are scant. Several genes coding for cement gland-specific proteins were identified, but only one of these showed database homology. This was a lysyl oxidase-like protein (lcp_LOX). LOX-like enzymes have been previously identified in the proteome of adult barnacle cement secretory tissue. We attempted to produce recombinant LOX in E. coli, in order to identify its role in cyprid cement polymerisation. We also produced two other cement gland proteins (lcp3_36k_3B8 and lcp2_57k_2F5). lcp2_57k_2F5 contained 56 lysine residues and constituted a plausible substrate for LOX. While significant quantities of soluble lcp3_36k_3B8 and lcp2_57k_2F5 were produced in E. coli, production of stably soluble lcp_LOX failed. A commercially sourced human LOX catalysed the crosslinking of lcp2_57k_2F5 into putative dimers and trimers, and this reaction was inhibited by lcp3_36k_3B8. Inhibition of the lcp_LOX:lcp2_57k_2F5 reaction by lcp3_36k_3B8 appeared to be substrate specific, with no inhibitory effect on the oxidation of cadaverine by LOX. The results demonstrate a possible curing mechanism for barnacle cyprid cement and, thus, provide a basis for a more complete understanding of larval adhesion for targeted control of marine biofouling and adhesives for niche applications.

Cell wall proteomic analysis of the cnidarian photosymbionts Breviolum minutum and Cladocopium goreaui.

The algal cell wall is an important cellular component that functions in defense, nutrient utilization, signaling, adhesion, and cell–cell recognition—processes important in the cnidarian–dinoflagellate symbiosis. The cell wall of symbiodiniacean dinoflagellates is not well characterized. Here, we present a method to isolate cell walls of Symbiodiniaceae and prepare cell‐wall‐enriched samples for proteomic analysis. Label‐free liquid chromatography–electrospray ionization tandem mass spectrometry was used to explore the surface proteome of two Symbiodiniaceae species from the Great Barrier Reef: Breviolum minutum and Cladocopium goreaui. Transporters, hydrolases, translocases, and proteins involved in cell‐adhesion and protein–protein interactions were identified, but the majority of cell wall proteins had no homologues in public databases. We propose roles for some of these proteins in the cnidarian–dinoflagellate symbiosis. This work provides the first proteomics investigation of cell wall proteins in the Symbiodiniaceae and represents a basis for future explorations of the roles of cell wall proteins in Symbiodiniaceae and other dinoflagellates.

A Novel Antimicrobial Peptides From Pine Needles of Pinus densiflora Sieb. et Zucc. Against Foodborne Bacteria.

Pine needles are used in several East Asian countries as food or traditional medicine. It contains functional components that exhibit a wide spectrum of pharmacological effects such as antioxidant, antimicrobial, anti-diabetic, and anti-inflammatory activities. We determined and characterized the novel antimicrobial peptides (AMPs) isolated from Pinus densiflora Sieb. et Zucc. The four active pine-needle (PN) peptides showed antimicrobial activity against foodborne bacteria with minimum inhibitory concentration (MIC) values within the range of 8–128 μg/ml. PN peptides showed no detectable hemolytic activity or cytotoxicity at the antimicrobial concentrations. The N-terminal amino acid sequence of the PN5 was identified using Edman degradation and Antimicrobial Peptide Database (APD) homology analysis showed that it was not identical to any other plant peptide. This suggests that PN5 can serve as an alternative therapeutic agent to be used in the food industry.

Transcriptome Analyses of Pre-parasitic and Parasitic Meloidogyne Chitwoodi Race 1 to Identify Putative Effector Genes

Meloidogyne chitwoodi is a root-knot nematode that is a major pest of potato in the northwestern United States. Due to the lack of resistance against root-knot nematodes in potato, research has been undertaken to understand the M. chitwoodi-potato interaction at the molecular level. To identify the nematode genes that are playing roles in parasitism, we have performed transcriptome analyses on pre-parasitic and parasitic M. chitwoodi juveniles in susceptible potato. We compared gene expression profiles and identified genes that were significantly up- or down-regulated during nematode parasitism. Because parasitism proteins are typically secreted by the nematode to facilitate infection of host roots, we focused on the genes that encoded proteins that were predicted to be secreted. We found that approximately 34% (43/127) of the genes in the predicted secretome encoded proteins with no significant homology in the public genome databases, and 12% (15/127) encoded either a known effector, putative effectors or putative esophageal gland cell proteins. The transcriptome analyses of M. chitwoodi at the pre-parasitic and parasitic life stages shed light on the genes involved in nematode parasitism.

Comparative Genomics Reveals Novel Target Genes towards Specific Control of Plant-Parasitic Nematodes.

Plant-parasitic nematodes cause extensive annual yield losses to worldwide agricultural production. Most cultivated plants have no known resistance against nematodes and the few bearing a resistance gene can be overcome by certain species. Chemical methods that have been deployed to control nematodes have largely been banned from use due to their poor specificity and high toxicity. Hence, there is an urgent need for the development of cleaner and more specific control methods. Recent advances in nematode genomics, including in phytoparasitic species, provide an unprecedented opportunity to identify genes and functions specific to these pests. Using phylogenomics, we compared 61 nematode genomes, including 16 for plant-parasitic species and identified more than 24,000 protein families specific to these parasites. In the genome of Meloidogyne incognita, one of the most devastating plant parasites, we found ca. 10,000 proteins with orthologs restricted only to phytoparasitic species and no further homology in protein databases. Among these phytoparasite-specific proteins, ca. 1000 shared the same properties as known secreted effectors involved in essential parasitic functions. Of these, 68 were novel and showed strong expression during the endophytic phase of the nematode life cycle, based on both RNA-seq and RT-qPCR analyses. Besides effector candidates, transcription-related and neuro-perception functions were enriched in phytoparasite-specific proteins, revealing interesting targets for nematode control methods. This phylogenomics analysis constitutes a unique resource for the further understanding of the genetic basis of nematode adaptation to phytoparasitism and for the development of more efficient control methods.

DGINN, an automated and highly-flexible pipeline for the detection of genetic innovations on protein-coding genes.

Adaptive evolution has shaped major biological processes. Finding the protein-coding genes and the sites that have been subjected to adaptation during evolutionary time is a major endeavor. However, very few methods fully automate the identification of positively selected genes, and widespread sources of genetic innovations such as gene duplication and recombination are absent from most pipelines. Here, we developed DGINN, a highly-flexible and public pipeline to Detect Genetic INNovations and adaptive evolution in protein-coding genes. DGINN automates, from a gene's sequence, all steps of the evolutionary analyses necessary to detect the aforementioned innovations, including the search for homologs in databases, assignation of orthology groups, identification of duplication and recombination events, as well as detection of positive selection using five methods to increase precision and ranking of genes when a large panel is analyzed. DGINN was validated on nineteen genes with previously-characterized evolutionary histories in primates, including some engaged in host-pathogen arms-races. Our results confirm and also expand results from the literature, including novel findings on the Guanylate-binding protein family, GBPs. This establishes DGINN as an efficient tool to automatically detect genetic innovations and adaptive evolution in diverse datasets, from the user's gene of interest to a large gene list in any species range.