Orphan genes are genes with no sequence homologues in other species. Here, we identified two orphan genes, namely, Tssor-3 and Tssor-4, in Plutella xylostella. Both genes contained a signal peptide sequence, suggestin...Orphan genes are genes with no sequence homologues in other species. Here, we identified two orphan genes, namely, Tssor-3 and Tssor-4, in Plutella xylostella. Both genes contained a signal peptide sequence, suggesting their functions as secreted proteins. Expression pattern analysis based on real-time quantitative PCR(qPCR) showed that both orphan genes were specifically expressed in all male gonads except the testes. The expression of both the orphan genes peaked at the male adult stage. Immunofluorescence assays suggested that the two proteins were seminal proteins, indicating their potential roles in male reproductive regulation. To further explain their functions, we knocked down the expression of these two genes by RNA interference(RNAi). The results showed that the expression of Tssor-3 and Tssor-4 was significantly downregulated at 24 h after injection compared to that of the controls. Biological assays showed that the number of laid eggs and the hatching rate of offspring eggs were significantly reduced when the expression of Tssor-3 and Tssor-4 was reduced, suggesting that the two orphan genes played a role in male fertility in P. xylostella. Our results provide evidence that orphan genes are involved in male reproductive regulation, which is important for male fitness during evolution.展开更多
Orphan genes that lack detectable homologues in other lineages could contribute to a variety of biological functions. However,their origination and function mechanisms remain largely unknown. Herein, through a compreh...Orphan genes that lack detectable homologues in other lineages could contribute to a variety of biological functions. However,their origination and function mechanisms remain largely unknown. Herein, through a comprehensive and systematic computational pipeline, we identified 893 orphan genes in the lineage of C. elegans, of which only a low fraction(0.9%) were derived from transposon elements. Six new protein-coding genes that de novo originated from non-coding DNA sequences in the genome of C. elegans were also identified. The authenticity and functionality of these orphan genes and de novo genes are supported by three lines of evidences, consisting of transcriptional data, and in silico proteomic data, and the fixation status data in wild populations. Orphan genes and de novo genes exhibited simple gene structures, such as, short in protein length, of fewer exons,and are frequently X-linked. RNA-seq data analysis showed these orphan genes are enriched with expression in embryo development and gonad, and their potential function in early development was further supported by gene ontology enrichment analysis results. Meanwhile, de novo genes were found to be with significant expression in gonad, and functional enrichment analysis of the co-expression genes of these de novo genes suggested they may be functionally involved in signaling transduction pathway and metabolism process. Our results presented the first systematic evidence on the evolution of orphan genes and de novo origin of genes in nematodes and their impacts on the functional and phenotypic evolution, and thus could shed new light on our appreciation of the importance of these new genes.展开更多
The adoptive transfer of T cells is a promising approach to treat cancers. Primary human T cells can be modified using viral and non-viral vectors to promote the specific targeting of cancer cells via the introduction...The adoptive transfer of T cells is a promising approach to treat cancers. Primary human T cells can be modified using viral and non-viral vectors to promote the specific targeting of cancer cells via the introduction of exogenous T-cell receptors(TCRs) or chimeric antigen receptors(CARs). This gene transfer displays the potential to increase the specificity and potency of the anticancer response while decreasing the systemic adverse effects that arise from conventional treatments that target both cancerous and healthy cells. This review highlights the generation of clinical-grade T cells expressing CARs for immunotherapy, the use of these cells to target B-cell malignancies and, particularly, the first clinical trials deploying the Sleeping Beauty gene transfer system, which engineers T cells to target CD19+ leukemia and non-Hodgkin's lymphoma.展开更多
基金supported by the Natural Science Foundation of Fujian Province, China (2020J01525)the National Natural Science Foundation of China (31320103922 and 31230061)the Major Science and Technology Projects in Fujian Province, China (2018NZ010100130)。
文摘Orphan genes are genes with no sequence homologues in other species. Here, we identified two orphan genes, namely, Tssor-3 and Tssor-4, in Plutella xylostella. Both genes contained a signal peptide sequence, suggesting their functions as secreted proteins. Expression pattern analysis based on real-time quantitative PCR(qPCR) showed that both orphan genes were specifically expressed in all male gonads except the testes. The expression of both the orphan genes peaked at the male adult stage. Immunofluorescence assays suggested that the two proteins were seminal proteins, indicating their potential roles in male reproductive regulation. To further explain their functions, we knocked down the expression of these two genes by RNA interference(RNAi). The results showed that the expression of Tssor-3 and Tssor-4 was significantly downregulated at 24 h after injection compared to that of the controls. Biological assays showed that the number of laid eggs and the hatching rate of offspring eggs were significantly reduced when the expression of Tssor-3 and Tssor-4 was reduced, suggesting that the two orphan genes played a role in male fertility in P. xylostella. Our results provide evidence that orphan genes are involved in male reproductive regulation, which is important for male fitness during evolution.
基金supported by EEgrid cluster of the University of Chicagosupported by National Natural Science Foundation of China(31600670 to W.Zhang,31670851 to B.Shen)
文摘Orphan genes that lack detectable homologues in other lineages could contribute to a variety of biological functions. However,their origination and function mechanisms remain largely unknown. Herein, through a comprehensive and systematic computational pipeline, we identified 893 orphan genes in the lineage of C. elegans, of which only a low fraction(0.9%) were derived from transposon elements. Six new protein-coding genes that de novo originated from non-coding DNA sequences in the genome of C. elegans were also identified. The authenticity and functionality of these orphan genes and de novo genes are supported by three lines of evidences, consisting of transcriptional data, and in silico proteomic data, and the fixation status data in wild populations. Orphan genes and de novo genes exhibited simple gene structures, such as, short in protein length, of fewer exons,and are frequently X-linked. RNA-seq data analysis showed these orphan genes are enriched with expression in embryo development and gonad, and their potential function in early development was further supported by gene ontology enrichment analysis results. Meanwhile, de novo genes were found to be with significant expression in gonad, and functional enrichment analysis of the co-expression genes of these de novo genes suggested they may be functionally involved in signaling transduction pathway and metabolism process. Our results presented the first systematic evidence on the evolution of orphan genes and de novo origin of genes in nematodes and their impacts on the functional and phenotypic evolution, and thus could shed new light on our appreciation of the importance of these new genes.
文摘The adoptive transfer of T cells is a promising approach to treat cancers. Primary human T cells can be modified using viral and non-viral vectors to promote the specific targeting of cancer cells via the introduction of exogenous T-cell receptors(TCRs) or chimeric antigen receptors(CARs). This gene transfer displays the potential to increase the specificity and potency of the anticancer response while decreasing the systemic adverse effects that arise from conventional treatments that target both cancerous and healthy cells. This review highlights the generation of clinical-grade T cells expressing CARs for immunotherapy, the use of these cells to target B-cell malignancies and, particularly, the first clinical trials deploying the Sleeping Beauty gene transfer system, which engineers T cells to target CD19+ leukemia and non-Hodgkin's lymphoma.
