So far, the monoclonal hypothesis of tumor occurrence and development cannot be justified. The genetic diversity selection hypothesis for the occurrence and development of lung cancer links Mendelian genetics with Darwin's theory of evolution, suggesting that the genetic diversity of tumor cell populations with polyclonal origins-monoclonal selection-subclonal expansion is the result of selection pressure. Normal cells acquire mutations in oncogenic driver genes and have a selective advantage over other cells, becoming tumor initiating cells; In the interaction with the tumor microenvironment (TME), the vast majority of initiating cells are recognized and killed by the human immune system. If immune escape occurs, the incidence of malignant tumors will greatly increase, and subclonal expansion, intratumour heterogeneity, etc. will occur. This article proposed the hypothesis of genetic diversity selection and analyzed its clinical significance.
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Humans ; Lung Neoplasms/genetics* ; Clinical Relevance ; Evolution, Molecular ; Mutation ; Tumor Microenvironment

Bombyx Batryticatus is a precious traditional Chinese animal drug commonly used in clinical practice in China, which has the effects of extinguishing wind, stopping convulsions, dispelling wind, relieving pain, resolving phlegm, and dissipating mass. The processing of Bombyx Batryticatus has a long history. As early as in the Liu Song period of the Southern and Northern Dynasties, there was a record of the processing of Bombyx Batryticatus with rice swill. In addition to the processing with bran, honey bran, and ginger juice, which are still used today, there are also processing methods such as rendering, flour processing, wine processing, salt processing, oil processing, charcoal, and red dates processing in ancient times. After processing, the fishy smell of Bombyx Batryticatus can be removed, and avoid nausea and vomiting caused by the direct taking. Furthermore, processing can also facilitate the removal of surface hairs and toxicity reduction, making the medicinal material crispy and easy to crush. Previous studies have shown that the main chemical constituents of Bombyx Batryticatus include protein polypeptides, sterols, and flavonoids, with anticonvulsant, anticoagulation, antithrombotic, anti-cancer, hypnotic, hypoglycemic, and other pharmacological effects. This paper reviewed the processing historical evolution, chemical constituents, and pharmacological effects of Bombyx Batryticatus to lay a foundation for the research on the processing mechanism, quality control, and active core substances of Bombyx Batryticatus.
Animals ; Bombyx ; China ; Evolution, Chemical ; Flavonoids ; Fruit

Objective: To assess the incidence of dengue fever and E gene evolution of dengue virus in Guangzhou in 2020 and understand the local epidemiological characteristics of dengue fever and spreading of dengue virus. Methods: The information of dengue fever cases in Guangzhou in 2020 was collected from Notifiable Infectious Disease System of Chinese Center for Disease Control and Prevention Information System. Serum samples from the cases were detected by real-time PCR. The E gene was sequenced and analyzed. Maximum likelihood phylogenetic trees were constructed using software MEGA 5.05. The statistical analysis was conducted using software SPSS 20.0. Results: A total of 33 dengue fever cases were reported in Guangzhou in 2020, including 31 (93.94%) imported cases and 2 (6.06%) local cases. Compared with the data during 2016 to 2019, the number of cases, overall incidence and local incidence all decreased with statistically significant differences (all P<0.05). The imported cases from Southeast Asia constituted 90.32% (28/31) of imported cases. The E gene sequences and the phylogenetic trees of imported and local cases demonstrated close relationship with the virus sequences from Southeast Asian, and they were less homologous with the sequences of dengue virus isolated in Guangzhou in previous years. Conclusions: The incidence of dengue in Guangzhou in 2020 was significantly affected by the imported cases, especially those from Southeast Asian countries. The study result demonstrated that dengue fever was not endemic in Guangzhou and it was caused by imported ones.
China/epidemiology* ; Dengue/epidemiology* ; Dengue Virus/genetics* ; Disease Outbreaks ; Evolution, Molecular ; Genotype ; Humans ; Phylogeny

To explore the different chloroplast genome characteristics of Sinopodophyllum hexandrum, five chloroplast genome sequences of S. hexandrum were compared. Its genome map, repeat sequence, codon preference, inverted repeat (IR)/single-copy (SC) boundary, alignment of chloroplast genome sequences and phylogenetic were analyzed using bioinformatics tools. The results showed that: the total length of five chloroplast genomes of S. hexandrum, with a typical tetrad structure, were 157 203-157 940 bp, and a total of 133-137 genes were annotated, reflecting the diversity of chloroplast genomes of S. hexandrum. Different chloroplast genomes of S. hexandrum has different simple sequence repeat (SSR), where simple repeat of single nucleotide of A/T were the majority among the SSR detected. The interspersed repetitive sequences included direct, palindromic and inverted repeats. The value of effective number of codon (ENc) which was analyzed by using codon bias was 51.14~51.17, the proportion of GC and GC3s was less than 50%, the codon usage pattern tended towards frequently use of A/U-ending bases. Genome sequences and the IR/SC boundaries of five chloroplast genomes of S. hexandrum were relatively conservative. Phylogenetic analysis showed that S. hexandrum and Podophyllum pettatum had the closest genetic relationship. In summary, the chloroplast genome characteristics and evolutionary relationship of different chloroplast genomes of S. hexandrum were obtained, which may facilitate the utilization, protection, variety identification and genetic evolution of S. hexandrum resources.
Phylogeny ; Genome, Chloroplast ; Chloroplasts/genetics* ; Genomics ; Evolution, Molecular

As a traditional animal drug, Hirudo is slightly toxic and has the effects of breaking blood stasis, dredging meridians, expelling stasis, and resolving mass. It has a long history of processing, and the early boiling records can be traced back to the Han Dynasty. More than ten processing methods such as frying, roasting, and lime processing appeared later. After processing, Hirudo is deodorized and modified in taste and becomes crispy, which is conducive to crushing and clinical application. At present, the reported components in Hirudo mainly include protein polypeptides, pteridines, and lipids, which have anti-coagulant, anti-thrombotic, anti-atherosclerotic, anti-tumor, and other pharmacological effects. This study reviewed the processing history evolution, chemical consti-tuents, and pharmacological effects of Hirudo to provide a reference for the related research on Hirudo.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Evolution, Chemical ; Leeches ; Thrombosis ; Restraint, Physical

Enzymes and cell factories are the core of industrial biotechnology. They play important roles in various fields such as medicine, chemical industry, food, agriculture, and energy. Usually, natural enzymes and cells need to be engineered to improve the catalytic efficiency, stability and enantioselectivity. Directed evolution makes it possible to rapidly improve the properties of enzymes and cell factories. Sensitive and reliable high-throughput screening approaches are the key for successful and efficient engineering of enzymes and cell factories. In this review, we first summarize the advantages and disadvantages of different screening methods and signal generation strategies as well as their application scope; we then describe the latest advances of ultra-high throughput screening technology applied in the directed evolution of enzymes and cell factories in the past three years. On this basis, we discuss the limiting factors that need to be further improved for high-throughput screening systems and forecast the future development trends of high-throughput screening methods, hoping that researchers in various fields including biotechnology and instrument development can cooperate closely to enhance the reliability and applicability of the high-throughput screening techniques.
Biotechnology ; Directed Molecular Evolution ; Enzymes ; High-Throughput Screening Assays ; Reproducibility of Results

Directed evolution is a cyclic process that alternates between constructing different genes and screening functional gene variants. It has been widely used in optimization and analysis of DNA sequence, gene function and protein structure. It includes random gene libraries construction, gene expression in suitable hosts and mutant libraries screening. The key to construct gene library is the storage capacity and mutation diversity, to screen is high sensitivity and high throughput. This review discusses the latest advances in directed evolution. These new technologies greatly accelerate and simplify the traditional directional evolution process and promote the development of directed evolution.
Base Sequence ; Directed Molecular Evolution ; Gene Library ; Mutation ; Proteins/genetics*

Laboratory evolution is an important approach to improve the performance of microorganisms. In the past decades, the methods for laboratory evolution have developed rapidly and applied widely. However, the commonly used evolution strategies for strains or specific proteins cannot achieve continuous mutation, and require multiple rounds of operation, therefore they are considered as a labor intensive process. The development of mutation and screening technologies have facilitated the development of continuous evolution in vivo and greatly improved the efficiency of laboratory evolution. The continuous in vivo evolution achieves in vivo mutation, perfectly combining mutation with screening to evolve a specific phenotype with minimal human intervention. This review summarizes the recent advances of in vivo continuous evolution technologies for either genome-scale mutation or evolution of specific proteins. The principles of these technologies and their applications are introduced. On this basis, the advantages and limitations of these technologies are discussed. We also give a perspective of future development of continuous in vivo evolution.
Directed Molecular Evolution ; Humans ; Mutation ; Phenotype ; Proteins

Adenosine diphosphate (ADP)-ribosylation is a unique post-translational modification that regulates many biological processes, such as DNA damage repair. During DNA repair, ADP-ribosylation needs to be reversed by ADP-ribosylhydrolases. A group of ADP-ribosylhydrolases have a catalytic domain, namely the macrodomain, which is conserved in evolution from prokaryotes to humans. Not all macrodomains remove ADP-ribosylation. One set of macrodomains loses enzymatic activity and only binds to ADP-ribose (ADPR). Here, we summarize the biological functions of these macrodomains in DNA damage repair and compare the structure of enzymatically active and inactive macrodomains. Moreover, small molecular inhibitors have been developed that target macrodomains to suppress DNA damage repair and tumor growth. Macrodomain proteins are also expressed in pathogens, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, these domains may not be directly involved in DNA damage repair in the hosts or pathogens. Instead, they play key roles in pathogen replication. Thus, by targeting macrodomains it may be possible to treat pathogen-induced diseases, such as coronavirus disease 2019 (COVID-19).
ADP-Ribosylation ; COVID-19/metabolism* ; DNA Repair/physiology* ; Evolution, Molecular ; Humans ; Models, Biological ; Models, Molecular ; N-Glycosyl Hydrolases/metabolism* ; Poly(ADP-ribose) Polymerases/metabolism* ; Protein Domains ; SARS-CoV-2/pathogenicity*

The amino acid sequence of ancestral enzymes from extinct organisms can be deduced through in silico approach termed ancestral sequence reconstruction (ASR). ASR usually has six steps, which are the collection of nucleic acid/amino acid sequences of modern enzymes, multiple sequence alignment, phylogenetic tree construction, computational deduction of ancestral enzyme sequence, gene cloning, and characterization of enzyme properties. This method is widely used to study the adaptation and evolution mechanism of molecules to the changing environmental conditions on planetary time scale. As enzymes play key roles in biocatalysis, this method has become a powerful method for studying the relationship among the sequence, structure, and function of enzymes. Notably, most of the ancestral enzymes show better temperature stability and mutation stability, making them ideal protein scaffolds for further directed evolution. This article summarizes the computer algorithms, applications, and commonly used computer software of ASR, and discusses the potential application in directed evolution of enzymes.
Amino Acid Sequence ; Evolution, Molecular ; Phylogeny ; Proteins/genetics* ; Sequence Alignment