LZ complexity distance of DNA sequences and its application in phylogenetic tree reconstruction

DNA sequences can be treated as finite-length symbol strings over a four-letter alphabet （A, C, T, G）. As a universal and computable complexity measure, LZ complexity is valid to describe the complexity of DNA sequences. In this study, a concept of conditional LZ complexity between two sequences is proposed according to the principle of LZ complexity measure. An LZ complexity distance metric between two nonnull sequences is defined by utilizing conditional LZ complexity. Based on LZ complexity distance, a phylogenetic tree of 26 species of placental mammals （Eutheria） with three outgroup species was reconstructed from their complete mitochondrial genomes. On the debate that which two of the three main groups of placental mammals, namely Primates, Ferungulates, and Rodents, are more closely related, the phylogenetic tree reconstructed based on LZ complexity distance supports the suggestion that Primates and Ferungulates are more closely related.     

Strand-biased Gene Distribution in Bacteria Is Related to both Horizontal Gene Transfer and Strand-biased Nucleotide Composition

Although strand-biased gene distribution(SGD) was described some two decades ago,the underlying molecular mechanisms and their relationship remain elusive.Its facets include,but are not limited to,the degree of biases,the strand-preference of genes,and the influence of background nucleotide composition variations.Using a dataset composed of 364 non-redundant bacterial genomes,we sought to illustrate our current understanding of SGD.First,when we divided the collection of bacterial genomes into non-polC and polC groups according to their possession of DnaE isoforms that correlate closely with taxonomy,the SGD of the polC group stood out more significantly than that of the non-polC group.Second,when examining horizontal gene transfer,coupled with gene functional conservation(essentiality) and expressivity(level of expression),we realized that they all contributed to SGD.Third,we further demonstrated a weaker G-dominance on the leading strand of the non-polC group but strong purine dominance(both G and A) on the leading strand of the polC group.We propose that strand-biased nucleotide composition plays a decisive role for SGD since the polC-bearing genomes are not only AT-rich but also have pronounced purine-rich leading strands,and we believe that a special mutation spectrum that leads to a strong purine asymmetry and a strong strand-biased nucleotide composition coupled with functional selections for genes and their functions are both at work.     

How territoriality affects the density of an egg predator： Habitat renovation and reintroduction as a method of conserving two endangered desert spring fish

Conservation of endangered sympatric species must be carefully executed to ensure that the protection of one species does not negatively impact the survival of another. Critically endangered Pecos gambusia Gambusia nobilis and Leon Springs pupfish Cyprinodon bovinus, which are endemic to a threatened desert spring habitat, exemplify one such scenario. Recently, this habitat has been expanded, and captively bred C. bovinus were released to repopulate an area historically known to contain this species. A previous study suggested that G. nobilis are detrimental to C. bovinus populations, due to their tendency to congregate near spawning pairs and feed on their eggs. Whether G. nobilis are attracted to territorial C. bovinus, regardless of spawning behavior, remains unclear. To determine this, the number of G. nobilis in occupied and unoccupied breeding territories of both wild and captively bred C. bovinus was measured. Gambusia nobilis densities were similar between unoccupied and occupied territorial sites, suggesting that they do not show a preference for C. bovinus territories. Regardless of habitat location or prior captivity, territorial C. bovinus significantly excluded G. nobilis within their direct vicinity （5 cm）, but not from their entire territory. Decreased G. nobilis density within the habitat may allow C. bovinus to defend their breeding territories more readily during the summer spawning season. This study provides empirical evidence of captively raised individuals behaving similarly to wild indi- viduals upon reintroduction to their natural habitat and support for conservation methods that focus on common limiting factors between endangered species [Current Zoology 60 （4）： 527-533, 2014].     

Stereotypes About Enterotype: the Old and New Ideas

In 2011, the term ‘‘enterotype" first appeared to the general public in Nature, which refers to stratification of human gut microbiota. However, with more studies on enterotypes conducted nowadays, doubts about the existence and robustness of enterotypes have also emerged. Here we reviewed current opinions about enterotypes from both conceptual and analytical points of view.We firstly illustrated the definition of the enterotype and various factors influencing enterotypes,such as diet, administration of antibiotics, and age. Then we summarized lines of evidence that pose the concept against the enterotype, and described the current methods for enterotype analysis.Finally, we showed that the concept of enterotype has been extended to other ecological niches.Based on current studies on enterotypes, it has been clear that more studies with larger sample sizes are needed to characterize the enterotypes. Improved computational methods are also required to build sophisticated models, reflecting the dynamics and resilience of enterotypes.     

中国广东汉族人群核苷酸修复基因hMTH1 遗传多态性研究

为研究中国南方汉族人群核苷酸修复基因hMTH1遗传多态性,应用聚合酶链反应-单链构象多态性技术检测172名健康人外周血白细胞hMTH1基因启动子及全部5个外显子多态性,并进行DNA测序。结果发现hMTH1基因启动子及外显子1序列保守,未见突变;外显子2第73位碱基存在T→C杂合型突变,基因型TT和TC频率分别为93.02%、6.98%,等位基因T和C频率分别为96.51%、3.49％;外显子3第45位遗传密码存在T→C杂合型突变,基因型TT和TC频率分别为95.35%、4.65%,等位基因T和C频率分别为97.67%、2.33%,该多态性为首次发现;外显子4第83位遗传密码存在G→A杂合型突变,基因型GG和GA频率分别为89.53%、10.47%,等位基因G和A频率分别为94.77%、5.23％;外显子5第119位氨基酸遗传密码存在C→T杂合型突变,基因型CC和CT频率分别为95.93%、4.07%,等位基因C和T频率分别为97.97%、2.03％。Abstract: In order to study the genetic polymorphisms of nucleotide repair gene hMTH1 in southern Chinese Han population, the polymorphisms of the gene’s promoter and its five exons among peripheral blood lymphocytes of 172 Chinese Han people were analyzed with polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing. The sequences of the promoter and exon 1 of hMTH1 gene were conserved. A T to C polymorphism was detected at the 73th base in exon2. The genotype frequencies of TT and TC were 93.02% and 6.98%, respectively. The allelic frequencies of T and C were 96.51% and 3.49％, respectively. A T to C polymorphism was detected at codon 45 in exon3, which was first reported. The genotype frequencies of TT and TC were 95.35% and 4.65%, respectively. The allelic frequencies of T and C were 97.67% and 2.33%, respectively. A G to A polymorphism was detected at codon 83 in exon4. The genotype frequencies of GG and GA were 89.53% and 10.47%, respectively. The allelic frequencies of G and A were 94.77% and 5.23％, respectively. A C to T polymorphism was detected at codon 119 in exon5. The genotype frequencies of CC and CT were 95.93% and 4.07%, respectively. The allelic frequencies of C and T were 97.97% and 2.03％, respectively.     

Experiment Research on Binocular Perceptual Characteristics around Peripheral Vision for Development of Head Mounted Display with Wide View

The head mounted display （HMD） is widely used in virtual reality technology. In common HMD, however, the binocular disparity is set to an equal fixed value in the entire range of view. Such HMD systems have several shortcomings when used for wide views. In this study, in order to realize a natural stereo sensation of HMD with wide view, we measure the characteristics of binocular stereo perception and binocular light perception. Results show that both the stereoacuity and light sensitivity decrease as the retina＇s eccentricity increases from fovea to periphery. However, the decrease of the stereoacuity is more rapid than that of the light sensitivity. These results suggest that the binocular disparity at the peripheral field should be small, otherwise double images would be observed instead of a stereo view. Based on the results we develop a relative binocular stereoacuity model which can be applied for the design of HMD systems with wide view.     

A/T-targeted somatic hypermutation: critique of the mainstream model

The "affinity maturation" of the humoral immune response is driven by antigen-activated somatic hypermutation (SHM) of the genes that encode antibody variable regions and the subsequent antigenic selection of mutant clones. The molecular mechanism of SHM is yet to be completely elucidated. SHM affects cytosine-guanine (C/G) and adenine-thymine (A/T) pairs with approximately equal frequency in vivo. The proposition that error-prone DNA-dependent DNA synthesis explains A/T-targeted hypermutagenesis seems to have mainstream support within the hypermutation research community at present. A major feature of SHM in vivo is that C/G hypermutation is strand unbiased, whereas A/T hypermutation is strand biased. We show that the "DNA-based polymerase error" model of A/T-targeted hypermutagenesis does not explain this important aspect of SHM.     

Atypical at skew in Firmicute genomes results from selection and not from mutation

The second parity rule states that, if there is no bias in mutation or selection, then within each strand of DNA complementary bases are present at approximately equal frequencies. In bacteria, however, there is commonly an excess of G (over C) and, to a lesser extent, T (over A) in the replicatory leading strand. The low G+C Firmicutes, such as Staphylococcus aureus, are unusual in displaying an excess of A over T on the leading strand. As mutation has been established as a major force in the generation of such skews across various bacterial taxa, this anomaly has been assumed to reflect unusual mutation biases in Firmicute genomes. Here we show that this is not the case and that mutation bias does not explain the atypical AT skew seen in S. aureus. First, recently arisen intergenic SNPs predict the classical replication-derived equilibrium enrichment of T relative to A, contrary to what is observed. Second, sites predicted to be under weak purifying selection display only weak AT skew. Third, AT skew is primarily associated with largely non-synonymous first and second codon sites and is seen with respect to their sense direction, not which replicating strand they lie on. The atypical AT skew we show to be a consequence of the strong bias for genes to be co-oriented with the replicating fork, coupled with the selective avoidance of both stop codons and costly amino acids, which tend to have T-rich codons. That intergenic sequence has more A than T, while at mutational equilibrium a preponderance of T is expected, points to a possible further unresolved selective source of skew.     

Repair of specific base pair mismatches formed during meiotic recombination in the yeast Saccharomyces cerevisiae.

Heteroduplexes formed between DNA strands derived from different homologous chromosomes are an intermediate in meiotic crossing over in the yeast Saccharomyces cerevisiae and other eucaryotes. A heteroduplex formed between wild-type and mutant genes will contain a base pair mismatch; failure to repair this mismatch will lead to postmeiotic segregation (PMS). By analyzing the frequency of PMS for various mutant alleles in the yeast HIS4 gene, we showed that C/C mismatches were inefficiently repaired relative to all other point mismatches. These other mismatches (G/G, G/A, T/T, A/A, T/C, C/A, A/A, and T/G) were repaired with approximately the same efficiency. We found that in spores with unrepaired mismatches in heteroduplexes, the nontranscribed strand of the HIS4 gene was more frequently donated than the transcribed strand. In addition, the direction of repair for certain mismatches was nonrandom.     

Photocleavage of DNA and photofootprinting of E. coli RNA polymerase bound to promoter DNA by azido-9-acridinylamines.

The long-wavelength ultraviolet (lambda approximately 420 nm) radiation induced reaction between 6-azido-2-methoxy-9-acridinylamines and supercoiled plasmid DNA results in single strand scissions and formation of covalent adducts (ratio approximately 1:10). By treating azidoacridine-photomodified DNA with piperidine at 90 degrees C, additional strand scissions are observed in a complex sequence dependent manner with an overall preference for T greater than or equal to G greater than C much greater than A. The resulting DNA fragments migrate as 5'-phosphates in polyacrylamide gels. Photofootprinting of the binding site of RNA-polymerase on promoter DNA is demonstrated with an azido-9-acridinylamino-octamethylene-9-aminoacridine. Similar experiments using 9-amino-6-azido-2-methoxyacridine indicate that this reagent recognizes changes in the DNA conformation induced by RNA polymerase binding, in relation to open complex formation.     

Base mismatch-specific endonuclease activity in extracts from Saccharomyces cerevisiae.

An endonuclease activity (called MS-nicking) for all possible base mismatches has been detected in the extracts of yeast, Saccharomyces cerevisiae. DNAs with twelve possible base mismatches at one defined position are cleaved at different efficiencies. DNA fragments with A/G, G/A, T/G, G/T, G/G, or A/A mismatches are nicked with greater efficiencies than C/T, T/C, C/A, and C/C. DNA with an A/C or T/T mismatch is nicked with an intermediate efficiency. The MS-nicking is only on one particular DNA strand, and this strand disparity is not controlled by methylation, strand break, or nature of the mismatch. The nicks have been mapped at 2-3 places at second, third, and fourth phosphodiester bonds 5' to the mispaired base; from the time course study, the fourth phosphodiester bond probably is the primary incision site. This activity may be involved in mismatch repair during genetic recombination.     

DNA recognition and binding by the Euplotes telomere protein.

The 51-kDa telomere protein from Euplotes crassus binds to the extreme terminus of macronuclear telomeres, generating a very salt-stable telomeric DNA-protein complex. The protein recognizes both the sequence and the structure of the telomeric DNA. To explore how the telomere protein recognizes and binds telomeric DNA, we have examined the DNA-binding specificity of the purified protein using oligonucleotides that mimic natural and mutant versions of Euplotes telomeres. The protein binds very specifically to the 3' terminus of single-stranded oligonucleotides with the sequence (T4G4) > or = 3 T4G2; even slight modifications to this sequence reduce binding dramatically. The protein does not bind oligonucleotides corresponding to the complementary C4A4 strand of the telomere or to double-stranded C4A4.T4G4-containing sequences. Digestion of the telomere protein with trypsin generates an N-terminal protease-resistant fragment of approximately 35 kDa. This 35-kDa peptide appears to comprise the DNA-binding domain of the telomere protein as it retains most of the DNA-binding characteristics of the native 51-kDa protein. For example, the 35-kDa peptide remains bound to telomeric DNA in 2 M KCl. Additionally, the peptide binds well to single-stranded oligonucleotides that have the same sequence as the T4G4 strand of native telomeres but binds very poorly to mutant telomeric DNA sequences and double-stranded telomeric DNA. Removal of the C-terminal 15 kDa from the telomere protein does diminish the ability of the protein to bind only to the terminus of a telomeric DNA molecule.     

Asymmetric directional mutation pressures in bacteria

Background

When there are no strand-specific biases in mutation and selection rates (that is, in the substitution rates) between the two strands of DNA, the average nucleotide composition is theoretically expected to be A = T and G = C within each strand. Deviations from these equalities are therefore evidence for an asymmetry in selection and/or mutation between the two strands. By focusing on weakly selected regions that could be oriented with respect to replication in 43 out of 51 completely sequenced bacterial chromosomes, we have been able to detect asymmetric directional mutation pressures.

Results

Most of the 43 chromosomes were found to be relatively enriched in G over C and T over A, and slightly depleted in G+C, in their weakly selected positions (intergenic regions and third codon positions) in the leading strand compared with the lagging strand. Deviations from A = T and G = C were highly correlated between third codon positions and intergenic regions, with a lower degree of deviation in intergenic regions, and were not correlated with overall genomic G+C content.

Conclusions

During the course of bacterial chromosome evolution, the effects of asymmetric directional mutation pressures are commonly observed in weakly selected positions. The degree of deviation from equality is highly variable among species, and within species is higher in third codon positions than in intergenic regions. The orientation of these effects is almost universal and is compatible in most cases with the hypothesis of an excess of cytosine deamination in the single-stranded state during DNA replication. However, the variation in G+C content between species is influenced by factors other than asymmetric mutation pressure.