Comparison of the chicken and zebra finch Z chromosomes shows evolutionary rearrangements

Using fluorescent in-situ hybridization (FISH) of zebra finch (Taeniopygia guttata) bacterial artificial chromosome (BAC) clones, we determined the chromosomal localizations of 14 zebra finch genes that are Z-linked in chickens: ATP5A1, CHD1, NR2F1, DMRT1, PAM, GHR, HSD17B4, NIPBL, ACO1, HINT1, SMAD2, SPIN, NTRK2 and UBE2R2. All 14 genes also map to the zebra finch Z chromosome, indicating substantial conservation of gene content on the Z chromosome in the two avian lineages. However, the physical order of these genes on the zebra finch Z chromosome differed from that of the chicken, in a pattern that would have required several inversions since the two lineages diverged. Eight of 14 zebra finch BAC DNA showed cross-hybridization to the W chromosome, usually to the entire W chromosome, suggesting that repetitive sequences are shared by the W and Z chromosomes. These repetitive sequences likely evolved in the finch lineage after it diverged from the Galliform lineage.     

Multilocus sequence typing of Streptococcus uberis provides sensitive and epidemiologically relevant subtype information and reveals positive selection in the virulence gene pauA

Control of the bovine mastitis pathogen Streptococcus uberis requires sensitive and epidemiologically meaningful subtyping methods that can provide insight into this pathogen's epidemiology and evolution. Development of a multilocus sequence typing (MLST) scheme based on six housekeeping and virulence genes allowed differentiation of 40 sequence types among 50 S. uberis isolates from the United States (n = 30) and The Netherlands (n = 20). MLST was more discriminatory than EcoRI or PvuII ribotyping and provided subtype data with better epidemiological relevance, e.g., by discriminating isolates with identical ribotypes obtained from different farms. Phylogenetic analyses of MLST data revealed indications of reticulate evolution between genes, preventing construction of a core phylogeny based on concatenated DNA sequences. However, all individual gene phylogenies clearly identified a distinct pauA-negative subtaxon of S. uberis for which housekeeping alleles closely resembled those of Streptococcus parauberis. While the average GC content for five genes characterized was between 0.38 and 0.40, pauA showed a considerably lower GC content (0.34), suggesting acquisition through horizontal transfer. pauA also showed a higher nonsynonymous/synonymous rate ratio (dN/dS) (1.2) compared to the other genes sequenced (dN/dS < 0.12), indicating positive selection in this virulence gene. In conclusion, our data show that (i) MLST provides for highly discriminatory and epidemiologically relevant subtyping of S. uberis; (ii) S. uberis has a recombinatorial population structure; (iii) phylogenetic analysis of MLST data reveals an S. uberis subtaxon resembling S. parauberis; and (iv) horizontal gene transfer and positive selection contribute to evolution of certain S. uberis genes, such as the virulence gene pauA.     

The role of LINEs and CpG islands in dosage compensation on the chicken Z chromosome

Most avian Z genes are expressed more highly in ZZ males than ZW females, suggesting that chromosome-wide mechanisms of dosage compensation have not evolved. Nevertheless, a small percentage of Z genes are expressed at similar levels in males and females, an indication that a yet unidentified mechanism compensates for the sex difference in copy number. Primary DNA sequences are thought to have a role in determining chromosome gene inactivation status on the mammalian X chromosome. However, it is currently unknown whether primary DNA sequences also mediate chicken Z gene compensation status. Using a combination of chicken DNA sequences and Z gene compensation profiles of 310 genes, we explored the relationship between Z gene compensation status and primary DNA sequence features. Statistical analysis of different Z chromosomal features revealed that long interspersed nuclear elements (LINEs) and CpG islands are enriched on the Z chromosome compared with 329 other DNA features. Linear support vector machine (SVM) classifiers, using primary DNA sequences, correctly predict the Z compensation status for >60% of all Z-linked genes. CpG islands appear to be the most accurate classifier and alone can correctly predict compensation of 63% of Z genes. We also show that LINE CR1 elements are enriched 2.7-fold on the chicken Z chromosome compared with autosomes and that chicken chromosomal length is highly correlated with percentage LINE content. However, the position of LINE elements is not significantly associated with dosage compensation status of Z genes. We also find a trend for a higher proportion of CpG islands in the region of the Z chromosome with the fewest dosage-compensated genes compared with the region containing the greatest concentration of compensated genes. Comparison between chicken and platypus genomes shows that LINE elements are not enriched on sex chromosomes in platypus, indicating that LINE accumulation is not a feature of all sex chromosomes. Our results suggest that CpG islands are not randomly distributed on the Z chromosome and may influence Z gene dosage compensation status.     

Molecular evolution of West Nile virus

Phylogenetic analysis and estimation of the rate of evolution of West Nile virus (WNV) were conducted. Sixty-eight nucleotide sequences of WNV E protein were used for the analysis. The rate of nucleotide substitution accumulation was 2.5 × 10^?4 substitutions per site per year. Phylogenetic analysis and estimation of WNV evolution time using molecular-clock methodology demonstrated that the WNV genotypes 1, 2, and 4 with an estimated time of divergence from the common precursor of approximately 2360, 2800, and 5950 years, respectively, circulate on the territory of the European part of Russia. The ratio of frequencies of nonsynonymous substitutions (dN) to synonymous substitutions (dS) can vary within 0.022–0.275 for certain WNV strains grouped according to geographical and/or phylogenetic traits. The highest values of dN/dS ratio were found for modern WNV isolates in Russia and in North America, which appeared in new natural biocenoses of these regions in the last 14 years. dN/dS estimation for WNV species shows that indices of intraspecific dN/dS variability can be used for detecting the presence of accelerated evolution of new WNV isolates. All this confirms the hypothesis that favorable conditions exist for wide distribution and rapid evolution of different WNV genotypes (that arose 2000–6000 years ago) in modern natural and climatic conditions.     

丙型肝炎病毒包膜区变异与感染慢性化关系的初步研究

目的 探讨丙型肝炎病毒(HCV)包膜区变异与其感染慢性化的关系。方法 3份HCV慢性感染者和3份急性感染者血标本，采用逆转录—聚合两链反应(RT—PCR)扩增HCV的E1区C端及E2区N端片段(573bp)，扩增产物进行克隆，以单链构象多态性(SSCP)和异质性双体(HD)分析对每份血清30个克隆的E1／E2区准种(quasispecies)进行筛选，挑选每份标本HCV的优势株与劣势株序列进行测定，分析非同义替换碱基数与同义替换碱基数比率(dN／dS，间接反映选择压力)和推导的氨基酸序列。结果 HCV慢性感染者病毒准种的复杂性和E2区dN／dS明显高于急性感染者。HCV慢性感染者的E2区氨基酸替换率(8．46％)比急性感染者(1．02％)更高，而两者的E1区氨基酸替换率(分别为2．74％和1．09％)均较低。尽管HVR1变异程度更高，但仍存在高度保守的氨基酸位点。结论 HCV持续性感染与准种复杂性增高和宿主对HVR1的免疫选择有关。     

Sex chromosome evolution in moths and butterflies

Lepidoptera, i.e. moths and butterflies, have a female heterogametic sex chromosome system, with most females having a WZ constitution while males are ZZ. Besides this predominant WZ/ZZ system, Z/ZZ, WZ₁Z₂/Z₁Z₁Z₂Z₂ and W₁W₂Z/ZZ systems also occur. Sex is determined by an unknown W-linked gene or genes in Bombyx mori, but by dosage-dependent and equally unknown Z-linked genes in all Z/ZZ species. The female heterogametic sex chromosome system has been conserved for at least 180 MY in the phylogenetic branch that combines Lepidoptera and Trichoptera. The W chromosome, which is present in most lepidopteran species, was incorporated in the sex chromosome system much later, about 90–100 MY ago. The Z chromosomes are highly conserved among Lepidoptera, much like the Z in birds or the X in mammals. The W, on the other hand, is evolving rapidly. It is crammed with repetitive elements which appear to have a high turnover rate but poor in or even devoid of protein-coding genes. It has frequently undergone fusion with autosomes or sporadically lost altogether.     

Sex bias and dosage compensation in the zebra finch versus chicken genomes: General and specialized patterns among birds

We compared global patterns of gene expression between two bird species, the chicken and zebra finch, with regard to sex bias of autosomal versus Z chromosome genes, dosage compensation, and evolution of sex bias. Both species appear to lack a Z chromosome–wide mechanism of dosage compensation, because both have a similar pattern of significantly higher expression of Z genes in males relative to females. Unlike the chicken Z chromosome, which has female-specific expression of the noncoding RNA MHM (male hypermethylated) and acetylation of histone 4 lysine 16 (H4K16) near MHM, the zebra finch Z chromosome appears to lack the MHM sequence and acetylation of H4K16. The zebra finch also does not show the reduced male-to-female (M:F) ratio of gene expression near MHM similar to that found in the chicken. Although the M:F ratios of Z chromosome gene expression are similar across tissues and ages within each species, they differ between the two species. Z genes showing the greatest species difference in M:F ratio were concentrated near the MHM region of the chicken Z chromosome. This study shows that the zebra finch differs from the chicken because it lacks a specialized region of greater dosage compensation along the Z chromosome, and shows other differences in sex bias. These patterns suggest that different avian taxa may have evolved specific compensatory mechanisms.The recent sequencing of the genome of a second bird species, the zebra finch (Taeniopygia guttata) (Warren et al. 2010), now allows important comparative studies to discern patterns of genome organization that are common to birds and distinct from those of other taxa. Here we compare patterns of sex bias and sex chromosome dosage compensation in the zebra finch and chicken (Gallus gallus). The avian chromosomes generally have conserved gene content (Shetty et al. 1999; Nanda et al. 2008), and the zebra finch and chicken have similar numbers of macro- and microchromosomes (Pigozzi and Solari 1998; Itoh and Arnold 2005). The female is heterogametic (ZW) and the male is homogametic (ZZ). The zebra finch and chicken Z chromosomes have similar sets of genes, but have experienced a significant rearrangement of gene order since the two lineages split (Itoh et al. 2006; Warren et al. 2010).Sex chromosome dosage compensation involves diverse sex-specific mechanisms that adjust the expressed dose of genes encoded on heteromorphic sex chromosomes, to offset the sex difference in expression that would otherwise result from the sex difference in copy number of sex chromosome genes (Birchler et al. 2006; Chang et al. 2006; Arnold et al. 2008). Dosage compensation mechanisms operate not only to reduce sex bias in expression of sex chromosome genes, but also to reduce the disparity of expressed dose of sex chromosome and autosomal (A) genes (Nguyen and Disteche 2005). Three different X chromosome-wide mechanisms of dosage compensation are reported for Caenorhabditis elegans, Drosophila melanogaster, and mammals, but all of these mechanisms are effective in reducing the expected sexual disparity of X gene expression. Birds show no chromosome-wide dosage compensation mechanism, based on small-scale and genome-wide analyses (Baverstock et al. 1982; Kuroda et al. 2001; McQueen et al. 2001; Kuroiwa et al. 2002; Ellegren et al. 2007; Itoh et al. 2007). In chickens, expression of Z gene mRNAs are, on average, about 1.4–1.6 times higher in males than females, even before gonadal differentiation, a remarkable sex difference for an entire sex chromosome (Arnold et al. 2008; Zhang et al. 2010). The lack of effective dosage compensation is reported also for the silkworm moth, another ZW system (Zha et al. 2009), suggesting an unexpected difference in selection pressures on XX/XY versus ZZ/ZW systems (Mank 2009).Although most chicken Z genes are expressed at higher levels in males than females, some genes show no sex bias, indicating that some mechanism compensates for the sexual disparity in gene copy number. Some compensated genes are concentrated in a region of the short arm of the chicken Z chromosome, near the MHM (male hypermethylated) locus (Melamed and Arnold 2007; Arnold et al. 2008; Mank and Ellegren 2009a,b; Melamed et al. 2009). The MHM locus encodes a non-coding RNA MHM that is expressed only in females, possibly because of the greater methylation of DNA near MHM in males (Teranishi et al. 2001). Moreover, the chromatin near MHM shows female-specific acetylation of histone 4 at lysine 16, a modification that is predicted to increase gene expression (Bisoni et al. 2005). These findings suggest that the ncRNA MHM may participate in a local dosage-compensation mechanism that increases expression of near-MHM genes in females. Here we present evidence that the putative MHM mechanism is not common to all birds, and present other evidence that regulation of sex bias in gene expression differs in zebra finch and chicken despite their common pattern of ineffective compensation of Z chromosome gene expression.     

Relationship between physical and genetic distances along the zebra finch Z chromosome

Nine bacterial artificial chromosomes containing genes linked to the Z chromosome of the zebra finch (Taeniopygia guttata) were localized using FISH on synaptonemal complex spreads. Their positions were correlated with those previously reported on the mitotic Z chromosome, showing a linear relationship between positions along the mitotic chromosome and its synaptonemal complex. Distances in cM between the genes were calculated using a cytological map of the crossing-over based on the distribution of MLH1 foci along the ZZ synaptonemal complex (MLH1-cM map). It is shown that physical and genetic distances lack a linear relationship along most of the chromosome length, due to clustering of crossover events around the telomeres. This relationship departs strongly from that observed in the chicken Z chromosome and reflects the existence of different recombination rates and patterns among birds in spite of wide genomic conservation.     

Chromosomal polymorphism and comparative painting analysis in the zebra finch

The zebra finch (Taeniopygia guttata) is often studied because of its interesting behaviour and neurobiology. Genetic information on this species has been lacking, making analysis of informative mutants difficult. Here we report on an improved cytological method for preparation of metaphase chromosomes suitable for fluorescent in situ hybridization of adult birds. We found that individual chicken chromosome paints usually hybridized to single zebra finch chromosomes, indicating only minor chromosomal rearrangements since the evolutionary divergence of these two species, and suggesting that the genomic location of chicken genes will predict the location of zebra finch orthologues. Chicken chromosome 1 appears to have split into two macrochromosomes in zebra finches, and chicken chromosome 4 paint hybridizes to a zebra finch macrochromosome and a microchromosome. This pattern was confirmed by mapping the androgen receptor (AR), which is located on chicken chromosome 4 but on a zebra finch microchromosome. We detected a telocentric/submetacentric polymorphism of chromosome 6 in our colony of zebra finches, and found that the polymorphism was inherited in a Mendelian pattern     

Molecular characterization of Korean Pepper mottle virus isolates and its relationship to symptom variations

The symptom variations among Korean Pepper mottle virus (PepMoV) isolates infecting pepper, tomato and potato were described and the cause of variations in relation to molecular variability were investigated. In addition, the entire genome of the 13 PepMoV isolates, collected from five provinces (Kyonggi, Chungnam, Gyeongnam, Jeonbuk and Jeonnam) in Korea, were determined and compared including the previously reported Korean-Vb isolate and 2 other PepMoV isolates isolated from America (CA and FL). Our results showed that the nucleotide sequence of all Korean isolates tested were nearly identical (98–99%) and only 94% similar to American isolates. In general, the complete nucleotide sequences and deduced polyprotein sequences indicated low genetic variation among isolates showing 0.1–3% nucleotide changes per site. However, based on ratio between nucleotide diversity values in nonsynonymous and synonymous position (dN/dS ratio) surprisingly, P1 and 6K2 genes showed relatively high nucleotide substitution ratio (0.8 and 1.0 nucleotide, respectively). When the 6K2 amino acid were aligned, there were 15 amino acid substitutions found in PepMoV-infected potato and only 1 amino acid change from two isolates of PepMoV-infected bell pepper. Interestingly, three isolates including isolate numbers 731, 205135 and 205136 that possessed different aa changes at 6K2 region also showed distinct symptom differentiation in indicator hosts and cosegregated in the phylogenetic analysis. These results further proved previous studies that P1 and 6K2 genes with other proteins might have some involvement on host specificity and pathogenicity.     

Highly conserved linkage homology between birds and turtles: Bird and turtle chromosomes are precise counterparts of each other

The karyotypes of birds, turtles and snakes are characterized by two distinct chromosomal components, macrochromosomes and microchromosomes. This close karyological relationship between birds and reptiles has long been a topic of speculation among cytogeneticists and evolutionary biologists; however, there is scarcely any evidence for orthology at the molecular level. To define the conserved chromosome synteny among humans, chickens and reptiles and the process of genome evolution in the amniotes, we constructed comparative cytogenetic maps of the Chinese soft-shelled turtle (Pelodiscus sinensis) and the Japanese four-striped rat snake (Elaphe quadrivirgata) using cDNA clones of reptile functional genes. Homology between the turtle and chicken chromosomes is highly conserved, with the six largest chromosomes being almost equivalent to each other. On the other hand, homology to chicken chromosomes is lower in the snake than in the turtle. Turtle chromosome 6q and snake chromosome 2p represent conserved synteny with the chicken Z chromosome. These results suggest that the avian and turtle genomes have been well conserved during the evolution of the Arcosauria. The avian and snake sex Z chromosomes were derived from different autosomes in a common ancestor, indicating that the causative genes of sex determination may be different between birds and snakes.Matsuda and Nishida-Umehara contributed equally to this work.     

Identification and localization of two genes on the chicken Z chromosome: implication of evolutionary conservation of the Z chromosome among avian species

A cDNA clone containing an insert of about 3.4 kb, pCIREBP, was isolated from the chicken liver cDNA library and identified as a clone for the chicken homologue of iron-responsive element-binding protein (IREBP). The deduced amino acid sequence showed 88% identity with that of the mouse IREBP and 17 out of the 20 active site residues of the pig heart mitochondrial aconitase were conserved. Another cDNA clone, pZOV3, containing an insert of about 4.5 kb was isolated from the chicken ovary cDNA library. This cDNA contained an open reading frame for 327 amino acid residues, whose sequence had partial similarity to two immunoglobulin superfamily proteins; mouse GP-70 and chicken HT7. Fluorescencein situ hybridization using corresponding genomic clones revealed that both genes are localized on the Z chromosome; the ZOV3 gene at the middle of the short arm and the IREBP gene at the boundary of heterochromatin on the long arm. Southern blot hybridization to male and female genomic DNA preparations from six species representing five avian genera suggested that these two genes are Z-linked in all the species tested.     

Non-homologous sex chromosomes of birds and snakes share repetitive sequences

Snake sex chromosomes provided Susumo Ohno with the material on which he based his theory of how sex chromosomes differentiate from autosomal pairs. Like birds, snakes have a ZZ male/ZW female sex chromosome system, in which the snake Z is a macrochromosome much the same size as the bird Z. However, the gene content shows clearly that the snake and bird Z chromosomes are completely non-homologous. The molecular aspect of W chromosome degeneration in snakes remains largely unexplored. We used comparative genomic hybridization to identify the female-specific region of the W chromosome in representative species of Australian snakes. Using this approach, we show that an increasingly complex suite of repeats accompanies the evolution of W chromosome heteromorphy. In particular, we found that while the python Liasis fuscus exhibits no sex-specific repeats and indeed, no cytologically recognizable sex-specific region, the colubrid Stegonotus cucullatus shows a large domain on the short arm of the W chromosome that consists of female-specific repeats, and the large W of Notechis scutatus is composed almost entirely of repetitive sequences, including Bkm and 18S rDNA-related elements. FISH mapping of both simple and complex probes shows patterns of repeat amplification concordant with the size of the female-specific region in each species examined. Mapping of intronic sequences of genes that are sex-linked in both birds (DMRT1) and snakes (CTNNB1) reveals massive amplification in discrete domains on the W chromosome of the elapid N. scutatus. Using chicken W chromosome paint, we demonstrate that repetitive sequences are shared between the sex chromosomes of birds and derived snakes. This could be explained by ancestral but as yet undetected shared synteny of bird and snake sex chromosomes or may indicate functional homology of the repeats and suggests that degeneration is a convergent property of sex chromosome evolution. We also establish that synteny of snake Z-linked genes has been conserved for at least 166 million years and that the snake Z consists of two conserved blocks derived from the same ancestral vertebrate chromosome.     

Comparison of the chicken and turkey genomes reveals a higher rate of nucleotide divergence on microchromosomes than macrochromosomes

A distinctive feature of the avian genome is the large heterogeneity in the size of chromosomes, which are usually classified into a small number of macrochromosomes and numerous microchromosomes. These chromosome classes show characteristic differences in a number of interrelated features that could potentially affect the rate of sequence evolution, such as GC content, gene density, and recombination rate. We studied the effects of these factors by analyzing patterns of nucleotide substitution in two sets of chicken-turkey sequence alignments. First, in a set of 67 orthologous introns, divergence was significantly higher in microchromosomes (chromosomes 11-38; 11.7% divergence) than in both macrochromosomes (chromosomes 1-5; 9.9% divergence; P = 0.016) and intermediate-sized chromosomes (chromosomes 6-10; 9.5% divergence; P = 0.026). At least part of this difference was due to the higher incidence of CpG sites on microchromosomes. Second, using 155 orthologous coding sequences we noted a similar pattern, in which synonymous substitution rates on microchromosomes (13.1%) were significantly higher than were rates on macrochromosomes (10.3%; P = 0.024). Broadly assuming neutrality of introns and synonymous sites, or constraints on such sequences do not differ between chromosomal classes, these observations imply that microchromosomal genes are exposed to more germ line mutations than those on other chromosomes. We also find that dN/dS ratios for genes located on microchromosomes (average, 0.094) are significantly lower than those of macrochromosomes (average, 0.185; P = 0.025), suggesting that the proteins of genes on microchromosomes are under greater evolutionary constraint.     

Evidence for the adaptive evolution of ORF5 gene of Porcine reproductive and respiratory syndrome virus isolated in China

Porcine reproductive and respiratory syndrome virus (PRRSV) ORF5 gene encoding an envelope glycoprotein involved in humoral immunity is the most variable protein-coding gene of PRRSV. The present study aimed to identify potential selective pressures acting on the ORF5 gene of PRRSV isolates of North American type prevalent in China. The non-synonymous to synonymous rate ratio ω (dN/dS) was employed as a measure of selective pressure at the codon level. An overall ω of 0.45 indicated negative (purifying) selection as the major driving force operating on the ORF5 gene during adaptation of the virus to swine. Determination of ω values for individual amino acids sites revealed 8 positively selected sites, most of them situated in the N-terminal ectodomain, indicating their potential role in the binding of virus to the cellular receptors. Further, 75 negatively selected sites were identified in the rest of molecule, probably as a result of functional or immunological constraints. Determination of potential N-glycosylation sites revealed 7 sites, four of which coincided with the positively selected ones. These results indicated that a specific adaptive evolution has operated on the ORF5 gene of Chinese PRRSV isolates. It is hoped that the disclosed adaptive sites might help identify a candidate antigenic epitope for the use in vaccine against this serious swine disease.     

The evolutionary fate of MULE-mediated duplications of host gene fragments in rice

DNA transposons are known to frequently capture duplicated fragments of host genes. The evolutionary impact of this phenomenon depends on how frequently the fragments retain protein-coding function as opposed to becoming pseudogenes. Gene fragment duplication by Mutator-like elements (MULEs) has previously been documented in maize, Arabidopsis, and rice. Here we present a rigorous genome-wide analysis of MULEs in the model plant Oryza sativa (domesticated rice). We identify 8274 MULEs with intact termini and target-site duplications (TSDs) and show that 1337 of them contain duplicated host gene fragments. Through a detailed examination of the 5% of duplicated gene fragments that are transcribed, we demonstrate that virtually all cases contain pseudogenic features such as fragmented conserved protein domains, frameshifts, and premature stop codons. In addition, we show that the distribution of the ratio of nonsynonymous to synonymous amino acid substitution rates for the duplications agrees with the expected distribution for pseudogenes. We conclude that MULE-mediated host gene duplication results in the formation of pseudogenes, not novel functional protein-coding genes; however, the transcribed duplications possess characteristics consistent with a potential role in the regulation of host gene expression.     

Small effective population sizes and rare nonsynonymous variants in potyviruses

Analysis of nucleotide sequence polymorphism in complete genomes of 12 species of potyviruses (single-stranded, positive-sense RNA viruses, family Potyviridae) revealed evidence that long-term effective population sizes of these viruses are on the order of 10⁴. Comparison of nucleotide diversity in non-coding regions and at synonymous and nonsynonymous sites in coding regions showed that purifying selection has acted to eliminate numerous deleterious mutations both at nonsynonymous sites and in non-coding regions. The ratio of nonsynonymous to synonymous polymorphic sites increased as a function of the number of genomes sampled, whereas mean gene diversity at nonsynonymous polymorphic sites decreased with increasing sample size at a substantially faster rate than does mean gene diversity at synonymous polymorphic sites. Very similar relationships were observed both in available genomic sequences of 12 potyvirus species and in subsets created by randomly sampling from among 98 TuMV genomes. Taken together, these observations imply that a greater proportion of nonsynonymous than of synonymous variants are relatively rare as the result of ongoing purifying selection, and thus many nonsynonymous variants are unlikely to be discovered without extensive sampling.     

Higher dN/dS ratios in the HCV core gene, but not in the E1/HVR1 gene, are associated with human immunodeficiency virus-associated immunosuppression

Coinfection with HCV and HIV is prevalent among former commercial blood donors in some rural areas in China. Genetic variability of the HCV core and E1/HVR1 was investigated in 23 patients chronically infected with HCV-1b, with or without concomitant HIV infection. Genetic variability in the core sequence was higher under HIV-associated immunocompromised conditions. Both the Shannon entropy values at each nucleotide position and the dN/dS values at each codon were statistically higher in HIV/HCV-coinfected patients with lower CD4+ T cell counts (p-values were <0.0001 and equal to 0.0372, respectively). The more significant difference of dN/dS value occurred in a specific subregion of the core gene that is enriched in CTL/Th epitopes (p?=?0.0083). The dN/dS values of full-length core antigen were found to be negatively correlated with the S/CO ratio of plasma anti-HCV antibodies. By contrast, no significant difference in genetic diversity/complexity and dN/dS values in the E1/HVR1 region was found between those two groups. These results suggest that the dN/dS ratio in the core gene, but not in the E1/HVR1 gene, is influenced more by host CD4+ T cell–mediated cellular immunity.     

Analyses on mutation patterns, detection of population bottlenecks, and suggestion of deleterious-compensatory evolution among members of the genus Potyvirus

Summary. Viruses of the family Potyviridae exhibited a robust single-nucleotide polymorphism profile at the between-species level, conforming to the neutral theory rule. However, the ratios of nonsynonymous to synonymous mutations (Ka/Ks) were relatively greater between-species than within-species in viral cistrons examined from members of the genus Potyvirus, indicating a relaxation on constraint. Judged by the McDonald and Kreitman’s test, the fixation frequencies for nonsynonymous mutations across the genomes of closely related potyviruses were greater than expected, suggesting population bottlenecks at speciation. These mutation patterns are best explained by a deleterious-compensatory model. *Formerly Institute of Virology and Environmental Microbiology.