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Background Abnormalities in cilia ultrastructure and function lead to a range of human phenotypes termed ciliopathies. Many tetratricopeptide repeat domain (TTC) family members have been reported to play critical roles in cilium organization and function. Results Here, we describe five unrelated family trios with multisystem ciliopathy syndromes, including situs abnormality, complex congenital heart disease, nephronophthisis or neonatal cholestasis. Through whole-exome sequencing and Sanger sequencing confirmation, we identified compound heterozygous mutations of TTC12 and TTC21B in six affected individuals of Chinese origin. These nonsynonymous mutations affected highly conserved residues and were consistently predicted to be pathogenic. Furthermore, ex vivo cDNA amplification demonstrated that homozygous c.1464 + 2 T > C of TTC12 would cause a whole exon 16 skipping. Both mRNA and protein levels of TTC12 were significantly downregulated in the cells derived from the patient carrying TTC12 mutation c.1464 + 2 T > C by real-time qPCR and immunofluorescence assays when compared with two healthy controls. Transmission electron microscopy analysis further identified ultrastructural defects of the inner dynein arms in this patient. Finally, the effect of TTC12 deficiency on cardiac LR patterning was recapitulated by employing a morpholino-mediated knockdown of ttc12 in zebrafish. Conclusions To the best of our knowledge, this is the first study reporting the association between TTC12 variants and ciliopathies in a Chinese population. In addition to nephronophthisis and laterality defects, our findings demonstrated that TTC21B should also be considered a candidate gene for biliary ciliopathy, such as TTC26, which further expands the phenotypic spectrum of TTC21B deficiency in humans.

The white-blotched river stingray (Potamotrygon leopoldi) is a cartilaginous fish native to the Xingu River, a tributary of the Amazon River system. It possesses a lot of unique biological features such as disc-like body shape, bizarre color pattern and living in freshwater habitat while most stingrays and their close relatives are sea dwellers. As a member of the Potamotrygonidae family, P. leopoldi bears evolutionary signification in fish phylogeny, niche adaptation and skeleton formation. In this study, we present its draft genome of 4.11 Gb comprised of 16,227 contigs and 13,238 scaffolds, which has contig N50 of 3,937 kilobases and scaffold N50 of 5,675 kilobases in size. Our analysis shows that P. leopoldi is a slow-evolving fish, diverged from elephant shark about 96 million years ago. We find that two gene families related to immune system, immunoglobulin heavy constant delta genes, and T-cell receptor alpha/delta variable genes, stand out expanded in P. leopoldi only, suggesting robustness in response to freshwater pathogens in adapting novel environments. We also identified the Hox gene clusters in P. leopoldi and discovered that seven Hox genes shared by five representative fishes are missing in P. leopoldi. The RNA-seq data from P. leopoldi and other three fish species demonstrate that fishes have a more diversified tissue expression spectrum as compared to the corresponding mammalian data. Our functional studies suggest that the lack of genes encoding vitamin D-binding protein in cartilaginous (both P. leopoldi and Callorhinchus milii) fishes could partly explain the absence of hard bone in their endoskeleton. Overall, this genome resource provides new insights into the niche-adaptation, body plan and skeleton formation of P. leopoldi as well as the genome evolution in cartilaginous fish.

Molecular characterizations, including microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP) showed strong associations in colorectal carcinoma (CRC) and provided a deeper understanding of the etiology of disease. However, the global relationship between epigenetic alternations and changes in mRNA expression in CRC remains largely undefined, especially regarding the roles of DNA methyltransferases (DNMTs). Here, we conducted a systematic network comparison to explore the global conservation between co-expressed and co-methylated modules. We successfully identified immune-related modules that were regulated by DNMTs and had strong associations with immune-infiltrating neutrophils and dendritic cells in CRC. Moreover, we found that genes in those modules were prognostic for CRC, with 97.1% (168/173) being significantly influenced by DNMTs. Thus, this study resolved an interaction between DNA methylation and mRNA expression through DNMTs. Additionally, we provided evidence that DNMTs control the global hypomethylation of oncogenes, including ALOX5AP and CSF3R that otherwise have high methylation in normal colons. Such genes were also more sensitive to DNMT changes, such as in CRC. Collectively, our analyzes provided a systems biology approach to investigate the association among different molecular phenotypes in diseases.

The cerebellum is critical for controlling motor and non-motor functions via cerebellar circuit that is composed of defined cell types, which approximately account for more than half of neurons in mammals. The molecular mechanisms controlling developmental progression and maturation processes of various cerebellar cell types need systematic investigation. Here, we analyzed transcriptome profiles of 21119 single cells of the postnatal mouse cerebellum and identified eight main cell clusters. Functional annotation of differentially expressed genes revealed trajectory hierarchies of granule cells (GCs) at various states and implied roles of mitochondrion and ATPases in the maturation of Purkinje cells (PCs), the sole output cells of the cerebellar cortex. Furthermore, we analyzed gene expression patterns and co-expression networks of 28 ataxia risk genes, and found that most of them are related with biological process of mitochondrion and around half of them are enriched in PCs. Our results also suggested core transcription factors that are correlated with interneuron differentiation and characteristics for the expression of secretory proteins in glia cells, which may participate in neuronal modulation. Thus, this study presents a systematic landscape of cerebellar gene expression in defined cell types and a general gene expression framework for cerebellar development and dysfunction.

BackgroundAlternative polyadenylation (APA) is a pervasive posttranscriptional mechanism regulating gene expression. However, the specific dysregulation of APA events and its potential biological or clinical significance in lung adenocarcinoma (LUAD) remain unclear.MethodsHere, we collected RNA-Seq data from two independent datasets: GSE40419 (n= 146) and The Cancer Genome Atlas (TCGA) LUAD (n= 542). The DaPars algorithm was employed to characterize the APA profiles in tumor and normal samples. Spearman correlation was used to assess the effects of APA regulators on 3′ UTR changes in tumors. The Cox proportional hazard model was used to identify clinically relevant APA events and regulators. We stratified 512 patients with LUAD in the TCGA cohort through consensus clustering based on the expression of APA factors.FindingsWe identified remarkably consistent alternative 3′ UTR isoforms between the two cohorts, most of which were shortened in LUAD. Our analyses further suggested that aberrant usage of proximal polyA sites resulted in escape from miRNA binding, thus increasing gene expression. Notably, we found that the 3′ UTR lengths of the mRNA transcriptome were correlated with the expression levels of APA factors. We further identified that CPSF2 and CPEB3 may serve as key regulators in both datasets. Finally, four LUAD subtypes according to different APA factor expression patterns displayed distinct clinical results and oncogenic features related to tumor microenvironment including immune, metabolic, and hypoxic status.InterpretationOur analyses characterize the APA profiles among patients with LUAD and identify two key regulators for APA events in LUAD, CPSF2 and CPEB3, which could serve as the potential prognostic genes in LUAD.

The white-blotched river stingray (Potamotrygon leopoldi) is a cartilaginous fish native to the Xingu River, a tributary of the Amazon River system. As a rare freshwater dwelling cartilaginous fish in the Potamotrygonidae family that no member has the genome sequencing information, P. leopoldi provides the evolutionary details in fish phylogeny, niche adaptation, and skeleton formation. In this study, we present its draft genome of 4.11 Gb comprised of 16,227 contigs and 13,238 scaffolds, which has contig N50 of 3937 kb and scaffold N50 of 5675 kb in size. Our analysis shows that P. leopoldi is a slow-evolving fish that diverged from elephant sharks about 96 million years ago. Our analyses show that two gene families related to the immune system, immunoglobulin heavy constant delta genes and T-cell receptor alpha/delta variable genes, stand out expanded in P. leopoldi only. We also identified the Hox gene clusters in P. leopoldi and discovered that seven Hox genes shared by five representative fishes are missing in P. leopoldi. The RNA sequencing data from P. leopoldi and other three fish species demonstrate that fishes have a more diversified tissue expression spectrum as compared to the corresponding mammalian data. Our functional studies suggest that the lack of genes encoding vitamin D-binding protein in cartilaginous (both P. leopoldi and Callorhinchus milii) fishes could partly explain the absence of hard bone in their endoskeleton. Overall, this genome resource provides new insights into the niche adaptation, body plan, and skeleton formation of P. leopoldi as well as the genome evolution in cartilaginous fish.

Background: Olfactory receptors (ORs) can bind odor molecules and play a crucial role in odor sensation. Due to the frequent gains and losses of genes during evolution, the number of OR members varies greatly among different species. However, whether the extent of gene gains/losses varies between marine mammals and related terrestrial mammals has not been clarified, and the factors that might underlie these variations are unknown. Results: To address these questions, we identified more than 10,000 members of the OR family in 23 mammals and classified them into 830 orthologous gene groups (OGGs) and 281 singletons. Significant differences occurred in the number of OR repertoires and OGGs among different species. We found that all marine mammals had fewer OR genes than their related terrestrial lineages, with the fewest OR genes found in cetaceans, which may be closely related to olfactory degradation. ORs with more gene duplications or loss events tended to be under weaker purifying selection. The average gain and loss rates of OR genes in terrestrial mammals were higher than those of mammalian gene families, while the average gain and loss rates of OR genes in marine mammals were significantly lower and much higher than those of mammalian gene families, respectively. Additionally, we failed to detect any one-to-one orthologous genes in the focal species, suggesting that OR genes are not well conserved among marine mammals. Conclusions: Marine mammals have experienced large numbers of OR gene losses compared with their related terrestrial lineages, which may result from the frequent birth-and-death evolution under varied functional constrains. Due to their independent degeneration, OR genes present in each lineage are not well conserved among marine mammals. Our study provides a basis for future research on the olfactory receptor function in mammals from the perspective of evolutionary trajectories.

BackgroundOlfactory receptors (ORs) can bind odor molecules and play a crucial role in odor sensation. Due to the frequent gains and losses of genes during evolution, the number of OR members varies greatly among different species. However, whether the extent of gene gains/losses varies between marine mammals and related terrestrial mammals has not been clarified, and the factors that might underlie these variations are unknown.ResultsTo address these questions, we identified more than 10,000 members of the OR family in 23 mammals and classified them into 830 orthologous gene groups (OGGs) and 281 singletons. Significant differences occurred in the number of OR repertoires and OGGs among different species. We found that all marine mammals had fewer OR genes than their related terrestrial lineages, with the fewest OR genes found in cetaceans, which may be closely related to olfactory degradation. ORs with more gene duplications or loss events tended to be under weaker purifying selection. The average gain and loss rates of OR genes in terrestrial mammals were higher than those of mammalian gene families, while the average gain and loss rates of OR genes in marine mammals were significantly lower and much higher than those of mammalian gene families, respectively. Additionally, we failed to detect any one-to-one orthologous genes in the focal species, suggesting that OR genes are not well conserved among marine mammals.ConclusionsMarine mammals have experienced large numbers of OR gene losses compared with their related terrestrial lineages, which may result from the frequent birth-and-death evolution under varied functional constrains. Due to their independent degeneration, OR genes present in each lineage are not well conserved among marine mammals. Our study provides a basis for future research on the olfactory receptor function in mammals from the perspective of evolutionary trajectories.

Background: Olfactory receptors (ORs) can bind odor molecules and play a crucial role in odor sensation. Due to the frequent gains and losses of genes during evolution, the number of OR members varies greatly among different species. However, it is still unclear whether the extent of gene gains/losses varies between marine mammals and related terrestrial mammals, and the factors that might underlie this variation are unknown. Results: To address these questions, we identified more than 10,000 members of the OR family in 23 mammals and classified them into 830 orthologous gene groups (OGGs). There were significant differences in the numbers of both OR repertoires and OGGs among different species. We found that all marine mammals had less OR genes than their related terrestrial lineages, with the least OR genes in cetaceans; this result may be closely related to olfactory degradation. ORs with more gene duplications or loss events tended to be under weaker purifying selection. The average gain and loss rates of OR genes in terrestrial mammals were higher than those of mammalian gene families, while the average gain and loss rates of OR genes in marine mammals were significantly lower and much higher, respectively, than those of mammalian gene families. Additionally, we failed to detect any one-to-one orthologous gene in the focal species, suggesting that OR genes are not well conserved among marine mammals. Conclusions: Marine mammals have experienced large numbers of OR genes compared with their related terrestrial lineages, which may result from the weaker purifying selection. Due to their independent degeneration, OR genes present in each lineage are not well conserved among marine mammals. Our study provides a basis for future research on the olfactory receptor function in mammals from the perspective of evolutionary trajectories.

Background: Pervasive perturbation of alternative splicing (AS) has been observed in cancer. RNA-binding proteins (RBPs) are master regulators of post-transcriptional processing, including AS. Thus, it is important to identify the associations between AS and RBPs. Results: Here, we comprehensively profiled aberrant splicing in hepatocellular carcinoma (HCC) and identified cancer phenotypes contributed by different mRNA isoforms. Additionally, we found that aberrant splicing impacted gene expression minimally, and was mostly regulated by the expression of RBPs. Remarkably, our analyses revealed that splicing-related pathways were perturbed by the altered AS events of RBPs. Further analyses indicated that 67 RBPs had double defects, both in AS and in gene expression, and had higher levels of mRNA expression in HCC. Therefore, we propose a model where the perturbation of AS might be triggered by autoregulatory and cross-regulatory networks among RBPs, such as ILF3 and UPF1. We demonstrate that RBPs can exacerbate HCC malignancy through AS and expression changes. To reveal associations between those two aspects, we performed stratification analyses of all patients based on the hub AS events of RBPs, and identified cancer subtypes with distinct clinical outcomes and RBP expressions. Additionally, we detected 60 RBPs with the highest expression levels in the subtype with the poorest survival rate. Conclusions: Our work details the interplay between the splicing and expression of RBPs, and highlights a key contributory role for RBPs in oncogenesis through widespread perturbations of AS. Funding: This work was supported by the following: the Natural Science Foundation of Zhejiang Province (No. LY15H160046), Ningbo Science and Technology Innovation Team Project (No. 2011B82016) and Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province (No. 2019E10020). Declaration of Interest: The authors declare no competing financial interests. Ethical Approval: MIssing

Additional file 2: Table S1. OR number distribution of 23 mammals. Intact genes indicate coding sequences starting from start codons and ending with stop codons without any interference mutations. Pseudogenes indicate sequences containing nonsense mutations, coding shifts, deletions in conserved regions, or combinatorial features. Truncated genes indicate sequences with partial sequences or located at the end of a contig. Truncated genes can also be pseudogenes. Pseudogene proportion refers to the number of pseudogenes divided by the total number of OR genes in the species.

Additional file 1: Figure S1. Comparison of estimated ω values of OGGs containing three marine lineages with the rest of the OGGs and all OGGs.

Background: Now the coronavirus disease 2019 (COVID-19) epidemic becomes a global phenomenon and its development concerns billions of peoples' lives. The development of the COVID-19 epidemic in China could be used as a reference for the other countries' control strategy. Methods: We used a classical susceptible-infected-recovered (SIR) model to forecast the development of the COVID-19 epidemic in China by nowcasting. The linear regression analyses were employed to predict the COVID-19 epidemic's inflexion point. Finally, we used a susceptible-exposed-infected-recovered (SEIR) model to simulate the development of the COVID-19 epidemic in China throughout 2020. Results: Our nowcasts show that the COVID-19 transmission rate started to slow down on January 30. The linear regression analyses further show that the inflexion point of this epidemic would arrive between February 17 and 18. The final SEIR model simulation forecasted that the COVID-19 epidemic would probably infect about 82,000 people and last throughout 2020 in China. We also applied our method to USA's and global COVID-19 data and the nowcasts show that the development of COVID-19 pandemic is not optimistic in the rest of 2020. Conclusion: The COVID-19 epidemic's scale in China is much smaller than the previous estimations. After implemented strict control and prevention measures, such as city lockdown, it took a week to slow down the COVID-19 transmission and about four weeks to really mitigate the COVID-19 prevalence in China.

Recently, a seminal model, called the omnigenic model, is proposed for understanding complex traits such as schizophrenia. In this study, we examined this model in Alzheimer’s disease and Parkinson’s disease from the perspectives of expression spectrum, shared disease-associated genes, common biological pathways, organ specificities, and network properties. Our results support the arguments brought forward by the omnigenic model. Although we only provided the limited evidence for the omnigenic model in neurodegenerative diseases, we hope that our effort can improve the understanding of these diseases and thus spur new ideas on how to prevent and treat them. The most important information we try to convey in our study is that there are more genes than we expected playing a role in the pathogenesis of neurodegenerative diseases and it is insufficient to study these diseases only focusing on some core genes or genetic pathways.

Shame and guilt seem to be two synonymous moral emotions but actually lead to contrasting human behaviors or behavioral tendencies. Shame drives people to hide or deny their wrongdoings while guilt drives people to amend their mistakes. How shame and guilt evolved in humans is still obscure. Here we present a computer model featured with reciprocal altruism and gregarious lifestyle for studying this question. We tested ten different strategies in our model and the pairwise contests show that shame-driven-hiding strategy can dominate the other strategies such as tit-for-tat and Pavlov in more than half of parameter combinations. The mathematical analysis of our model demonstrates that shame-driven-hiding strategy is an evolutionary stable strategy within a group as long as hiding can let an individual evade the retaliations to his wrongdoings. However, the problem of hiding is that it reduces an individual's social circle, i.e. living in a smaller group. Our analysis also shows that guilt-driven-amending strategy can outperform shame-driven-denying strategy at both individual and group levels if the cooperative behavior is sustainable within a group (b/(b-c) < T/n). Thus, we propose that shame is more adaptive at the individual level while guilt is more advantageous in the context of intergroup competition.

Summary: Dysfunction of noradrenergic (NA) neurons is associated with a number of neuronal disorders. Diverse neuronal subtypes can be generated by direct reprogramming. However, it is still unknown how to convert non-neuronal cells into NA neurons. Here, we show that seven transcription factors (TFs) (Ascl1, Phox2b, AP-2α, Gata3, Hand2, Nurr1, and Phox2a) are able to convert astrocytes and fibroblasts into induced NA (iNA) neurons. These iNA neurons express the genes required for the biosynthesis, release, and re-uptake of noradrenaline. Moreover, iNA neurons fire action potentials, receive synaptic inputs, and control the beating rate of co-cultured ventricular myocytes. Furthermore, iNA neurons survive and integrate into neural circuits after transplantation. Last, human fibroblasts can be converted into functional iNA neurons as well. Together, iNA neurons are generated by direct reprogramming, and they could be potentially useful for disease modeling and cell-based therapies. : Li et al. identified seven transcription factors that convert mouse astrocytes, fibroblasts, and human fibroblasts into induced noradrenergic (iNA) neurons. The iNA neurons are functional and integrate into neural circuits after transplantation. Single-cell RNA sequencing results showed that the transcriptome of iNA neurons converted from astrocytes and fibroblast are similar. Keywords: induced noradrenergic neurons, iNA neurons, direct neural reprogramming, astrocytes-to-neuron conversion, fibroblast-to-neuron conversion, transcription factors, noradrenaline release, mouse ventricular myocytes, optogenetic stimulation, cell transplantation, single-cell RNA sequencing

Thanks to the microarray technology, our understanding of transcriptome evolution at the genome level has been considerably advanced in the past decade. Yet, further investigation was challenged by several technical limitations of this technology. Recent innovation of next-generation sequencing, particularly the invention of RNA-seq technology, has shed insightful lights on resolving this problem. Though a number of statistical and computational methods have been developed to analyze RNA-seq data, the analytical framework specifically designed for evolutionary genomics remains an open question. In this article we develop a new method for estimating the genome expression distance from the RNA-seq data, which has explicit interpretations under the model of gene expression evolution. Moreover, this distance measure takes the data overdispersion, gene length variation, and sequencing depth variation into account so that it can be applied to multiple genomes from different species. Using mammalian RNA-seq data as example, we demonstrated that this expression distance is useful in phylogenomic analysis.

Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to beta group of coronavirus and was first discovered in 2012. MERS-CoV can infect multiple host species and cause severe diseases in human. We conducted a series of phylogenetic and bioinformatic analyses to study the evolution dynamics of MERS-CoV among different host species with genomic data. Our analyses show: 1) 28 potential recombinant sequences were detected and they can be classified into seven potential recombinant types; 2) The spike (S) protein of MERS-CoV was under strong positive selection when MERS-CoV transmitted from their natural host to human; 3) Six out of nine positive selection sites detected in spike (S) protein are located in its receptor-binding domain which is in direct contact with host cells; 4) MERS-CoV frequently transmitted back and forth between human and camel after it had acquired the human-camel infection capability. Together, these results suggest that potential recombination events might have happened frequently during MERS-CoV’s evolutionary history and the positive selection sites in MERS-CoV’s S protein might enable it to infect human.

Human U2OS osteosarcoma cells were first derived from a tibial osteosarcoma of a teenage girl. They are a good cell model for osteosarcoma research in vitro. We compared the expression profiles of osteosarcoma cells after they were treated with estradiol and glucocorticoid, respectively.We used published microarray data to compare the expression profiles of human osteosarcoma cells treated with estradiol and glucocorticoid. We investigated their differences and similarities with various bioinformatics tools. Oncogenes and tumor-suppressor genes differentially expressed after the hormone treatments were identified using online databases. The expression levels of cellular markers for proliferation and apoptosis were also compared before and after treatment with estradiol or glucocorticoid.Genes in human osteosarcoma cells differentially expressed after treatment with estradiol or glucocorticoid were detected. Our analysis showed that their similarity is more functionally prominent than their difference. Both estradiol and glucocorticoid can inhibit purine metabolic and biosynthetic pathway in human osteosarcoma cells. We also identified oncogenes and tumor-suppressor genes among the differentially expressed genes. The functional enrichment analyses of the identified cancer-associated genes suggests that estradiol has antagonistic effects on regulation of cell proliferation, while glucocorticoid can both arrest the cell cycle and prompt apoptosis. The effect of estradiol or glucocorticoid treatment on expression levels of cellular markers for proliferation and apoptosis support this argument.Our study suggests that glucocorticoid is more efficient in controlling osteosarcoma cell proliferation and apoptosis than estradiol.

Due to the continuous tightening of various regulations for conserving energy and protecting the environment, the weight reduction of and automobile body becomes an increasingly important issue. In order to reduce the weight of an automobile, we have brought forward a method of replacing the simple structure with the tailor-welded blank (TWB), in which a design process is appropriately defined for a front side rail. Focusing on the thickness determination of TWB, we have deduced the constraint inequalities of strength, bending stiffness, and torsion stiffness to prevent the thickness from decreasing unboundedly due to the lightweight requirement, thus reducing the weight of the front side rail satisfying the design demands of these three factors. The full-width frontal impact simulation of the whole car after redesign in the front side rails has been performed to verify vital performances such as deformation mode, energy absorption, and acceleration.

A variational full-field method is presented in this paper for the free vibration analysis of open circular cylindrical laminated shells supported at discrete points. A differential equation in matrix form is developed using the first-order shear deformable theory of shells, and rotary inertia is included. The displacement fields are defined by using very high-order interpolating polynomials and a large number of preselected nodal points on the reference surface of the shell. Each nodal point has 5 degrees of freedom, three displacement components, and two components of the rotation of the normal to the reference surface. The stiffness and mass matrices are obtained using the strain and kinetic energy functions. The numerical results are calculated for shallow and deep circular cylindrical panels with four-, six-, and eight-point supports along the two parallel straight edges. The values of the natural frequency obtained from the present method show good agreement with published data in the literature.

The operating mechanism in natural ecosystem gives us a lot of inspiration in exploring the complex interactions and evolution rules on industry cluster and technology community. In this paper, we first described the structure and operation mechanism of ecological community in natural word, then studied the technology innovation community and its support environment by using the theory of ecology. Finally, we analyzed the situation and characteristics of technology innovation in China's auto industry and carried out a case study.

The general secretion (Sec) pathway plays a prominent role in bacterial protein export, and the accessory component SecDF has been shown to improve transportation efficiency. Inspection of Streptomyces coelicolor genome reveals the unexpected presence of two different forms of secDF homologous genes: one in fused form (secDF) and the other in separated form (secD and secF). However, the functional role of two SecDF homologs in S. coelicolor has not yet been determined. Transcriptional analysis of secDF homologs reveals that these genes are constitutively expressed. However, the transcript levels of secD and secF are much higher than that of secDF in S. coelicolor. Deletion of secDF or/and secD/secF in S. coelicolor did result in reduced secretion efficiency of Xylanase A and Amylase C, suggesting that they may have redundant functions for Sec-dependent translocation pathway. Moreover, our results also indicate that SecD/SecF plays a more prominent role than SecDF in protein translocation. Evolutionary analysis suggests that the fused and separated SecDF homologs in Streptomyces may have disparate evolutionary ancestries. SecD/SecF may be originated from vertical transmission of existing components from ancestor of Streptomyces species. However, SecDF may be derived from bacterial ancestors through horizontal gene transfer. Alternately, it is also plausible that SecDF may have arisen through additional gene duplication and fusion events. The acquisition of a second copy may confer a selective benefit to Streptomyces by enhancing protein transport capacity. Taken together, our results provide new insights into the potential biological function and evolutionary aspects of the prokaryotic SecDF complex.