抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Motivation: In 2001 and 2002, we published two papers (Bioinformatics, 17, 282--283, Bioinformatics, 18, 77--82) describing an ultrafast protein sequence clustering program called cd-hit. This program can efficiently cluster a huge protein database with millions of sequences. However, the applications of the underlying algorithm are not limited to only protein sequences clustering, here we present several new programs using the same algorithm including cd-hit-2d, cd-hit-est and cd-hit-est-2d. Cd-hit-2d compares two protein datasets and reports similar matches between them; cd-hit-est clusters a DNA/RNA sequence database and cd-hit-est-2d compares two nucleotide datasets. All these programs can handle huge datasets with millions of sequences and can be hundreds of times faster than methods based on the popular sequence comparison and database search tools, such as BLAST.

Availability: http://cd-hit.org

Contact: [email protected]

Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences

KEGG(Kyoto Encyclopedia of Genes and Genomes)〔和文〕 (特集 ゲノム医学の現在と未来--基礎と臨床) -- (データベース)

https://www.cell.com/cell/pdf/S0092-8674(07)00594-6.pdf

PCNA, the Maestro of the Replication Fork

▪ Abstract The yeast SIR protein complex has been implicated in transcription silencing and suppression of recombination. The Sir complex represses transcription at telomeres, mating-type loci, and ribosomal DNA. Unlike SIR3 and SIR4, the SIR2 gene is highly conserved in organisms ranging from archaea to humans. Interestingly, Sir2 is active as an NAD+-dependent deacetylase, which is broadly conserved from bacteria to higher eukaryotes. In this review, we discuss the role of NAD+, the unusual products of the deacetylation reaction, the Sir2 structure, and the Sir2 chemical inhibitors and activators that were recently identified. We summarize the current knowledge of the Sir2 homologs from different organisms, and finally we discuss the role of Sir2 in caloric restriction and aging.

The Sir2 Family of Protein Deacetylases

Publisher Summary Transcription initiation is a key point in the regulation of the expression of most genes. The centerpiece of the molecular mechanism of eukaryal gene transcription is the preinitiation complex (PIC), which assembles on the promoter. The eukaryal PIC consists of a multisubunit enzyme RNA polymerase (RNAP) and general transcription factors (GTFs), as well as a large (and ever-growing) number of other auxiliary proteins. The archaeal transcription PIC is homologous to the eukaryal one; however, it is a much simpler system, requiring only the RNA polymerase and two GTFs: the TATA binding protein (TBP) and the transcription factor B (TFB) (the homolog of eukaryal TFIIB). Recent crystallographic studies have shown that the structures of the preinitiation complexes consisting of TBP, TFIIB, and a promoter fragment are essentially the same in Archaea and Eukarya. Archaeal DNA-dependent RNAP consists of approximately 12 subunits, which have high degree of sequence identity with their analogs from eukaryal Pol I, Pol II, and Pol III. Thus, the archaeal transcription PIC is amenable to structural investigations and represents a simplified model with which to study the underlying stereochemical principles of nonbacterial gene transcription. This chapter presents preparation procedures for various components of transcription PIC from three species of Archaea: Sulfolobus acidocaldarius , Sulfolobus shibatae , and Pyrococcus furiosus .

Preparation of components of archaeal transcription preinitiation complex.

DNA is duplicated within a complex macromolecular machine. Insights into how replication begins and how this is coordinated with progression of DNA synthesis come from a diverse range of sources.

Molecular biology: prime-time progress.

Expression of eukaryotic nuclear encoded tRNA genes requires two transcription factors, TFIIIB and TFIIIC. To determine if the highly evolutionarily diverged parasitic protozoan Trypanosoma brucei possesses any analogous factors, trypanosome nuclear extracts were prepared. Using these extracts in gel-retardation assays on trypanosome tRNA genes we detected three specific protein-DNA complexes, a highly retarded species and a less retarded pair of complexes. Introduction of mutations into the B box of a lysyl tRNA gene greatly reduced formation of all three complexes. Footprinting studies indicated that all complexes protected the B box of the tRNA gene from cleavage. The most highly retarded complex protected both the A and B boxes from DNasel cleavage. The less retarded pair of complexes showed footprints on the B box alone and the lowest B box specific complex is shown to be resistant to the polyanion heparin. All three complexes are demonstrated to induce bends in the DNA on binding.

/pdf/trypanosome-nuclear-factors-which-bind-to-internal-promoter-1d790v580r.pdf

Trypanosome nuclear factors which bind to internal promoter elements of tRNA genes

https://www.cell.com/molecular-cell/pdf/S1097-2765(20)30893-5.pdf

Multi-scale architecture of archaeal chromosomes

In all organisms, the DNA sequence and the structural organization of chromosomes affect gene expression. The extremely thermophilic crenarchaeon Sulfolobus has one circular chromosome with three origins of replication. We previously revealed that this chromosome has defined A and B compartments that have high and low gene expression, respectively. As well as higher levels of gene expression, the A compartment contains the origins of replication. To evaluate the impact of three-dimensional organization on genome evolution, we characterized the effect of replication origins and compartmentalization on primary sequence evolution in eleven Sulfolobus species. Using single-nucleotide polymorphism analyses, we found that distance from an origin of replication was associated with increased mutation rates in the B but not in the A compartment. The enhanced polymorphisms distal to replication origins suggest that replication termination may have a causal role in their generation. Further mutational analyses revealed that the sequences in the A compartment are less likely to be mutated, and that there is stronger purifying selection than in the B compartment. Finally, we applied the Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) to show that the B compartment is less accessible than the A compartment. Taken together, our data suggest that compartmentalization of chromosomal DNA can influence chromosome evolution in Sulfolobus. We propose that the A compartment serves as a haven for stable maintenance of gene sequences, while sequences in the B compartment can be diversified. Analysis of eleven Sulfolobus strains reveals that chromosome organization affects mutation rates in this species. 

Stephen D. Bell

Papers

Preparation of components of archaeal transcription preinitiation complex.

Molecular biology: prime-time progress.

Trypanosome nuclear factors which bind to internal promoter elements of tRNA genes

Multi-scale architecture of archaeal chromosomes

Chromosome organization affects genome evolution in Sulfolobus archaea