Evolution of the Major Pilus Gene Cluster of Haemophilus influenzae

Haemophilus influenzae is a ubiquitous colonizer of the human respiratory tract and causes diseases ranging from otitis media to meningitis. Many H. influenzae isolates express pili (fimbriae), which mediate adherence to epithelial cells and facilitate colonization. The pilus gene (hif) cluster of H. influenzae type b maps between purE and pepN and resembles a pathogenicity island: it is present in invasive strains, absent from the nonpathogenic Rd strain, and flanked by direct repeats of sequence at the insertion site. To investigate the evolution and role in pathogenesis of the hif cluster, we compared the purE-pepN regions of various H. influenzae laboratory strains and clinical isolates. Unlike Rd, most strains had an insert at this site, which usually was the only chromosomal locus of hif DNA. The inserts are diverse in length and organization: among 20 strains, nine different arrangements were found. Several nontypeable isolates lack hif genes but have two conserved open reading frames (hicA and hicB) upstream of purE; their inferred products are small proteins with no data bank homologs. Other isolates have hif genes but lack hic DNA or have combinations of hif and hic genes. By comparing these arrangements, we have reconstructed a hypothetical ancestral genotype, the extended hif cluster. The hif region of INT1, an invasive nontypeable isolate, resembles the hypothetical ancestor. We propose that a progenitor strain acquired the extended cluster by horizontal transfer and that other variants arose as deletions. The structure of the hif cluster may correlate with colonization site or pathogenicity.     

Hox Gene Loss during Dynamic Evolution of the Nematode Cluster

HOX GENES ARE IMPORTANT: their central role in anterior-posterior patterning provides a framework for molecular comparison of animal body plan evolution. The nematode Caenorhabditis elegans stands out as having a greatly reduced Hox gene complement. To address this, orthologs of C. elegans Hox genes were identified in six species from across the Nematoda, and they show that rapid homeodomain sequence evolution is a general feature of nematode Hox genes. Some nematodes express additional Hox genes belonging to orthology groups that are absent from C. elegans but present in other bilaterian animals. Analysis of the genomic environment of a newly identified Brugia malayi Hox6-8 ortholog (Bm-ant-1) revealed that it lay downstream of the Bm-egl-5 Hox gene and that their homeodomain exons are alternately cis spliced to the same 5' exon. This organization may represent an intermediate state in Hox gene loss via redundancy. The Hox clusters of nematodes are the product of a dynamic mix of gene loss and rapid sequence evolution, with the most derived state observed in the model C. elegans.     

Adaptive Evolution within Gut Microbiomes of Healthy People

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凤尾蕨科植物rbcL基因的适应性进化分析

为深入理解蕨类植物辐射式物种分化的分子适应机制,在时间框架下,采用位点模型和分支-位点模型对凤尾蕨科植物rbcL基因的进化式样进行了分析.通过比较模型M1a/M2a和M7/M8,在氨基酸水平上共鉴定出6个正选择位点:1491、251M、255V、282F、359S和375F,其中位点282F对维持Rubisco功能有重要作用.分别检验凤尾蕨科的附生分支和水蕨类分支发现,前者不具适应性进化位点,而后者有两个位点(230A和247C)经历正选择.相对于荫蔽的光条件,水生生境可能对RbcL亚基的选择作用更强.另外,基于UCLD分子钟模型估算出的风尾蕨科各分支分化时间表明,该科物种丰富度的辐射式增长发生在新生代渐新世,推测古、始新世最热事件可能对物种分化的形成也产生一定作用.这对认识薄囊蕨类如何应对被子植物兴起导致的陆地生态系统改变具重要意义.     

细鳞苔科psbA基因的适应性进化分析

在时间框架下,采用机理式模型(Mechanistic model)和MEC模型(Mechanistic-empirical combination model)以及Datamonkey对细鳞苔科psbA基因的进化式样进行了分析.结果均未检测到统计上显著的正选择位点,显示负选择对细鳞苔科psbA基因起主导作用.另外,基于UCLD分子钟估算出的细鳞苔科各分支分歧时间表明,该科物种丰富度的辐射式增长发生在新生代渐新世.     

DNA Methylation in an Enhancer Region of the FADS Cluster Is Associated with FADS Activity in Human Liver

Levels of omega-6 (n-6) and omega-3 (n-3), long chain polyunsaturated fatty acids (LcPUFAs) such as arachidonic acid (AA; 20∶4, n-6), eicosapentaenoic acid (EPA; 20∶5, n-3) and docosahexaenoic acid (DHA; 22∶6, n-3) impact a wide range of biological activities, including immune signaling, inflammation, and brain development and function. Two desaturase steps (Δ6, encoded by FADS2 and Δ5, encoded by FADS1) are rate limiting in the conversion of dietary essential 18 carbon PUFAs (18C-PUFAs) such as LA (18∶2, n-6) to AA and α-linolenic acid (ALA, 18∶3, n-3) to EPA and DHA. GWAS and candidate gene studies have consistently identified genetic variants within FADS1 and FADS2 as determinants of desaturase efficiencies and levels of LcPUFAs in circulating, cellular and breast milk lipids. Importantly, these same variants are documented determinants of important cardiovascular disease risk factors (total, LDL, and HDL cholesterol, triglycerides, CRP and proinflammatory eicosanoids). FADS1 and FADS2 lie head-to-head (5′ to 5′) in a cluster configuration on chromosome 11 (11q12.2). There is considerable linkage disequilibrium (LD) in this region, where multiple SNPs display association with LcPUFA levels. For instance, rs174537, located ∼15 kb downstream of FADS1, is associated with both FADS1 desaturase activity and with circulating AA levels (p-value for AA levels = 5.95×10⁻⁴⁶) in humans. To determine if DNA methylation variation impacts FADS activities, we performed genome-wide allele-specific methylation (ASM) with rs174537 in 144 human liver samples. This approach identified highly significant ASM with CpG sites between FADS1 and FADS2 in a putative enhancer signature region, leading to the hypothesis that the phenotypic associations of rs174537 are likely due to methylation differences. In support of this hypothesis, methylation levels of the most significant probe were strongly associated with FADS1 and, to a lesser degree, FADS2 activities.     

蕨类植物叶绿体rps4基因的适应性进化分析

在原核生物和植物叶绿体中,RPS4(ribosomal protein small subunit4)在核糖体30S小亚基形成起始过程中发挥重要作用;该蛋白在植物中由叶绿体rps4基因编码。为验证蕨类植物在白垩纪适应被子植物兴起而发生分化的观点,本文以23种蕨类植物为研究对象,利用分支模型、位点模型和分支位点模型对其叶绿体rps4基因进化适应性进行分析。分支模型检测到4个可能存在正选择的分支;位点模型和分支位点模型虽然没有检测出正选择位点,但是位点模型检测出了85个负选择位点。通过研究我们仅仅得出a、b两个代表水龙骨类的分支处于正选择压力下,这与水龙骨类在白垩纪发生辐射式演化的理论相一致。同时rps4基因处于强烈的负选择压力这一事实表明该基因的功能与结构已经趋于稳定。     

Evolution of CpG Islands within the myc Gene Family

CpG islands are discrete regions of DNA with significantly greater frequencies of CpG doublets than bulk genomic DNA. They are most frequently associated with the 5′-ends of housekeeping genes and are involved in the regulation of their expression. In this study, the structure and evolution of CpG islands within genes of the myc family were evaluated with the protein-coding sequences of animals and their transducing viruses. These evaluations relied on a gene tree for the entire myc family to test the origins of CpG islands within their two protein-coding exons. Overall, CG-very rich and CG-rich islands are associated with exon 2 of the different myc genes of warm-blooded vertebrates and with exon 3 of the N-myc and s-myc sequences of mammals, but not birds. These overall distributions of well-developed islands can be related to the major transitions of the CG-rich genomes of warm-blooded vertebrates from the CG-poor ones of other animals. In turn, the greater variability of well-developed islands within exon 3 of the N-myc gene and among the different retrogenes of the myc family can be attributed to their reduced functional constraints, as evidenced by their limited and very restricted patterns of expression, respectively.     

凤尾蕨科旱生蕨类rbcL基因的适应性进化和共进化分析

核酮糖-1,5-二磷酸羧化酶/加氧酶（Rubisco,EC 4.1.1.39）是植物参与光合作用的关键酶,其大亚基由叶绿体rbcL基因编码。为深入理解凤尾蕨科植物对干旱生境的分子适应机制,本研究以53种凤尾蕨科旱生植物的rbcL基因为对象,展开适应性进化和共进化研究。采用位点间可变ω比值模型以及SLAC、REL和FEL等方法进行的适应性进化分析显示：在氨基酸水平上共有15个正选择位点（66S、84E、139L、235G、245I、252A、273Y、295K、296N、299M、307G、330E、349S、365F、404A）,其中位点245I、252A和273Y对维持Rubisco功能起重要作用。共进化分析共鉴定出2组共进化位点,分别由139L、273Y、295K和273Y、295K、349S组成,这些氨基酸位点间的共进化方式与蛋白质的疏水性和分子量都显著相关。以上结果一方面支持基于ω比值检验DNA编码序列发生适应性进化的有效性,另一方面也提示凤尾蕨科植物对干旱生境的适应可能与rbcL基因的适应性进化有关。     

Adaptive Evolution and Frequent Gene Conversion in the Brain Expressed X-Linked Gene Family in Mammals

This work examines the molecular evolution of a brain-expressed X-linked gene family in the mammalian genomes of human, chimp, macaque, mouse, rat, dog, and cow. The gene structures are well conserved across family members and among the mammals in that all five members have three exons with the first two exons untranslated. Furthermore, the five members are arranged tandemly on chromosome X with Bex5, Bex1, Bex2 on the negative strand and Bex4, Bex3 on the positive strand, and this physical arrangement remains conserved among species. Sequence analyses indicate that gene conversion has been frequent and ongoing among Bex1-4, occurring in multiple species independently. All gene conversions in different species between Bex1 and Bex4, and between Bex2 and Bex3, appear to be limited to the upstream regions of the third exon, whereas the gene conversions occurred independently in different species between Bex1 and Bex2 and cover only the third exon. Bex5 appears to have little exchange of genetic information with other members, possibly due to its distance from other members. The GC content decreases from 5′-UTR, intron 1, intron 2, coding region, to 3′-UTR, reflecting faithfully the frequency of gene conversion in different regions of the Bex genes. Sequence analyses also suggest that both relaxed selective constraint and positive selection have acted on the Bex members after duplication. In particular, Bex3 shows strong evidence of positive selection and seems to have evolved a new gene function after gene duplication.     

Gene Conversion Facilitates the Adaptive Evolution of Self-Resistance in Highly Toxic Newts

Reconstructing the histories of complex adaptations and identifying the evolutionary mechanisms underlying their origins are two of the primary goals of evolutionary biology. Taricha newts, which contain high concentrations of the deadly toxin tetrodotoxin (TTX) as an antipredator defense, have evolved resistance to self-intoxication, which is a complex adaptation requiring changes in six paralogs of the voltage-gated sodium channel (Na_v) gene family, the physiological target of TTX. Here, we reconstruct the origins of TTX self-resistance by sequencing the entire Na_v gene family in newts and related salamanders. We show that moderate TTX resistance evolved early in the salamander lineage in three of the six Na_v paralogs, preceding the proposed appearance of tetrodotoxic newts by ∼100 My. TTX-bearing newts possess additional unique substitutions across the entire Na_v gene family that provide physiological TTX resistance. These substitutions coincide with signatures of positive selection and relaxed purifying selection, as well as gene conversion events, that together likely facilitated their evolution. We also identify a novel exon duplication within Na_v1.4 encoding an expressed TTX-binding site. Two resistance-conferring changes within newts appear to have spread via nonallelic gene conversion: in one case, one codon was copied between paralogs, and in the second, multiple substitutions were homogenized between the duplicate exons of Na_v1.4. Our results demonstrate that gene conversion can accelerate the coordinated evolution of gene families in response to a common selection pressure.     

Unveiling of Novel Radiations within Trichodesmium Cluster by hetR Gene Sequence Analysis

The filamentous nonheterocystous cyanobacterial genus Katagnymene is a common diazotrophic component of tropical and subtropical oceans. To assess the phylogenetic affiliation of this taxon, two partial 16S rRNA gene sequences and 25 partial hetR gene sequences originating from the genera Katagnymene and Trichodesmium collected from open, surface waters of the Atlantic, Indian, and Pacific oceans were compared. Single trichomes or colonies were identified morphologically by using light microscopy and then used directly as templates in hetR PCR analyses. In addition, three cultured strains, identified as Katagnymene pelagica, Katagnymene spiralis, and Trichodesmium sp., were examined. The data show that the genus Katagnymene is in the Trichodesmium cluster and that K. pelagica Lemmermann and K. spiralis Lemmermann are most likely one species, despite their different morphologies. Phylogenetic analyses also unveiled four distinct clusters in the Trichodesmium cluster, including one novel cluster. Our findings emphasize the conclusion that known morphological traits used to differentiate marine nonheterocystous cyanobacteria at the genus and species levels correlate poorly with genetic data, and a revision is therefore suggested.     

植物居群的基因流动态及其相关适应进化的研究进展

生物自然居群间的基因流不但可以阻止遗传分化以维持物种的完整性,而且也能积极响应生物多样化的进程。理解与基因流相关的适应性进化及其内在机理将有助于我们更好地认识生物物种形成和多样化的原始动力以及真正原因。该文通过对植物种内和种间居群基因流动态进行讨论,阐述了近年来有关植物基因流动态的一些重要理论观念和研究进展,以期为相关领域动态及趋势研究提供参考。     

植物居群的基因流动态及其相关适应进化的研究进展

生物自然居群间的基因流不但可以阻止遗传分化以维持物种的完整性, 而且也能积极响应生物多样化的进程。理解与基因流相关的适应性进化及其内在机理将有助于我们更好地认识生物物种形成和多样化的原始动力以及真正原因。该文通过对植物种内和种间居群基因流动态进行讨论, 阐述了近年来有关植物基因流动态的一些重要理论观念和研究进展, 以期为相关领域动态及趋势研究提供参考。     

Rapid Adaptive Evolution of the Tumor Suppressor Gene Pten in an Insect Lineage

The Pten gene was initially identified in humans as a tumor suppressor. It has since been shown to play important roles in the control of cell size, cell motility, apoptosis, and organ size, and it has also been implicated in aging. Pten is highly conserved among organisms as diverse as nematodes, insects, and vertebrates. In contrast, a phylogenetic analysis by maximum likelihood of a 133-amino acid region showed an average nonsynonymous-to-synonymous rate ratio of 10.4 for Pten in the lineage leading to parasitoid wasps of the Nasonia genus, indicating very strong positive selection. A previous study identified Pten as a potential QTL candidate gene for differences in male wing size in Nasonia. Most of the amino acid replacements that occurred in the Nasonia lineage cluster in a small region of the protein surface, suggesting that they might be involved in an interaction between Pten and another protein. The phenotypic changes due to Pten are not yet known, although it is not associated with known differences in male wing size. Introgression of Pten from one species to another does affect longevity, but a causal relationship is not established. [Reviewing Editor: Dr. Willie J. Swanson]     

Adaptive Evolution of the Hox Gene Family for Development in Bats and Dolphins

Bats and cetaceans (i.e., whales, dolphins, porpoises) are two kinds of mammals with unique locomotive styles and occupy novel niches. Bats are the only mammals capable of sustained flight in the sky, while cetaceans have returned to the aquatic environment and are specialized for swimming. Associated with these novel adaptations to their environment, various development changes have occurred to their body plans and associated structures. Given the importance of Hox genes in many aspects of embryonic development, we conducted an analysis of the coding regions of all Hox gene family members from bats (represented by Pteropus vampyrus, Pteropus alecto, Myotis lucifugus and Myotis davidii) and cetaceans (represented by Tursiops truncatus) for adaptive evolution using the available draft genome sequences. Differences in the selective pressures acting on many Hox genes in bats and cetaceans were found compared to other mammals. Positive selection, however, was not found to act on any of the Hox genes in the common ancestor of bats and only upon Hoxb9 in cetaceans. PCR amplification data from additional bat and cetacean species, and application of the branch-site test 2, showed that the Hoxb2 gene within bats had significant evidence of positive selection. Thus, our study, with genomic and newly sequenced Hox genes, identifies two candidate Hox genes that may be closely linked with developmental changes in bats and cetaceans, such as those associated with the pancreatic, neuronal, thymus shape and forelimb. In addition, the difference in our results from the genome-wide scan and newly sequenced data reveals that great care must be taken in interpreting results from draft genome data from a limited number of species, and deep genetic sampling of a particular clade is a powerful tool for generating complementary data to address this limitation.     

Adaptive Evolution of the First Extra Exon in the Murid Rodent Prolactin Gene Family

The prolactin gene family in rodents consists of multiple members that coordinate the processes of reproduction and pregnancy. Some members of this family acquired one or two additional exons between exon 2 and exon 3 of the prototypical 5-exon, 4-intron structure, but the evolutionary importance of this insertion is unclear. Here, we focus on those members and survey this question by molecular evolutionary methods. Phylogenetic analysis shows that those members cluster into two distinct groups. Further analysis shows that the two groups of genes originated before the divergence of mouse and rat but after that of rodents from other mammals. We compared the d _N/d _S values for each branch of the gene tree but found no evidence to support positive selection for any branch. We found strong evidence, however, that one site (11E) of the 13 sites of the first extra exon underwent positive selection by the site-specific models of the maximum-likelihood method. Combining our molecular evolutionary analysis with other known functional evidence, we believe that the insertion of the extra exon implies some functional adaptation.     

Valinomycin Biosynthetic Gene Cluster in Streptomyces: Conservation,Ecology and Evolution

Many Streptomyces strains are known to produce valinomycin (VLM) antibiotic and the VLM biosynthetic gene cluster (vlm) has been characterized in two independent isolates. Here we report the phylogenetic relationships of these strains using both parsimony and likelihood methods, and discuss whether the vlm gene cluster shows evidence of horizontal transmission common in natural product biosynthetic genes. Eight Streptomyces strains from around the world were obtained and sequenced for three regions of the two large nonribosomal peptide synthetase genes (vlm1 and vlm2) involved in VLM biosynthesis. The DNA sequences representing the vlm gene cluster are highly conserved among all eight environmental strains. The geographic distribution pattern of these strains and the strict congruence between the trees of the two vlm genes and the housekeeping genes, 16S rDNA and trpB, suggest vertical transmission of the vlm gene cluster in Streptomyces with no evidence of horizontal gene transfer. We also explored the relationship of the sequence of vlm genes to that of the cereulide biosynthetic genes (ces) found in Bacillus cereus and found them highly divergent from each other at DNA level (genetic distance values≥95.6%). It is possible that the vlm gene cluster and the ces gene cluster may share a relatively distant common ancestor but these two gene clusters have since evolved independently.     

Heterochromatic Stellate Gene Cluster in Drosophila Melanogaster: Structure and Molecular Evolution

The 30-kb cluster comprising close to 20 copies of tandemly repeated Stellate genes was localized in the distal heterochromatin of the X chromosome. Of 10 sequenced genes, nine contain undamaged open reading frames with extensive similarity to protein kinase CK2 β-subunit; one gene is interrupted by an insertion. The heterochromatic array of Stellate repeats is divided into three regions by a 4.5-kb DNA segment of unknown origin and a retrotransposon insertion: the A region (~14 Stellate genes), the adjacent B region (approximately three Stellate genes), and the C region (about four Stellate genes). The sequencing of Stellate copies located along the discontinuous cluster revealed a complex pattern of diversification. The lowest level of divergence was detected in nearby Stellate repeats. The marginal copies of the A region, truncated or interrupted by an insertion, escaped homogenization and demonstrated high levels of divergence. Comparison of copies in the B and C regions, which are separated by a retrotransposon insertion, revealed a high level of diversification. These observations suggest that homogenization takes place in the Stellate cluster, but that inserted sequences may impede this process.