A roadmap of tandemly arrayed genes in the genomes of human, mouse, and rat

Tandemly arrayed genes (TAGs) play an important functional and physiological role in the genome. Most previous studies have focused on individual TAG families in a few species, yet a broad characterization of TAGs is not available. Here we identified all TAGs in the genomes of humans, mouse, and rat and performed a comprehensive analysis of TAG distribution, TAG sizes, TAG orientations and intergenic distances, and TAG functions. TAGs account for about 14-17% of all genes in the genome and nearly one-third of all duplicated genes, highlighting the predominant role that tandem duplication plays in gene duplication. For all species, TAG distribution is highly heterogeneous along chromosomes and some chromosomes are enriched with TAG forests, whereas others are enriched with TAG deserts. The majority of TAGs are of size 2 for all genomes, similar to the previous findings in Caenorhabditis elegans, Arabidopsis thaliana, and Oryza sativa, suggesting that it is a rather general phenomenon in eukaryotes. The comparison with the genome patterns shows that TAG members have a significantly higher proportion of parallel gene orientation in all species, corroborating Graham's claim that parallel orientation is the preferred form of orientation in TAGs. Moreover, TAG members with parallel orientation tend to be closer to each other than all neighboring genes in the genome with parallel orientation. The analyses of Gene Ontology function indicate that genes with receptor or binding activities are significantly overrepresented by TAGs. Computer simulation reveals that random gene rearrangements have little effect on the statistics of TAGs for all genomes. Finally, the average proportion of TAGs shows a trend of increase with the increase of family sizes, although the correlation between TAG proportions in individual families and family sizes is not significant.     

More genes in vertebrates?

With the acquisition of complete genome sequences from several animals, there is renewed interest in the pattern of genome evolution on our own lineage. One key question is whether gene number increased during chordate or vertebrate evolution. It is argued here that comparing the total number of genes between a fly, a nematode and human is not appropriate to address this question. Extensive gene loss after duplication is one complication; another is the problem of comparing taxa that are phylogenetically very distant. Amphioxus and tunicates are more appropriate animals for comparison to vertebrates. Comparisons of clustered homeobox genes, where gene loss can be identified, reveals a one to four mode of evolution for Hox and ParaHox genes. Analyses of other gene families in amphioxus and vertebrates confirm that gene duplication was very widespread on the vertebrate lineage. These data confirm that vertebrates have more genes than their closest invertebrate relatives, acquired through gene duplication. abbreviations IHGSC, International Human Genome Sequencing Consortium; TCESC, The C. elegans Sequencing Consortium.     

RHR转录因子家族起源、功能以及进化机制的研究进展

转录因子是一类能够通过与基因特异性序列进行结合,从而调控基因转录与表达的蛋白质,对细胞的生物学活性具有重要的调节作用。RHR (Rel-homology region,RHR)转录因子家族属于IF (immunoglobulin fold)转录因子超家族最主要的成员,其成员含有保守的Rel结构域和IPT (immunoglobulin-like fold)结构域。作为古老的转录因子家族,RHR家族成员随着物种演化,通过基因的复制、突变和沉默,不断分化出新型同源基因的同时也伴随着基因的丢失。自然选择导致了各家族成员不同的进化速率,并且在一些功能结构域上展现出了特殊的进化机制。然而,目前有关RHR家族起源和分化的综述比较少见。本文综述了RHR家族各成员的分布、分类、功能及家族进化等方面的研究成果,以期为研究整个转录因子家族的演化机制和物种之间的进化关系提供参考和新的思路。     

Fifteen Million Years of Evolution in the Oryza Genus Shows Extensive Gene Family Expansion

In analyzing gene families in the whole-genome sequences available for O. sativa （AA）, O. glaberrima （AA）, and O. brachyantha （FF）, we observed large size expansions in the AA genomes compared to FF genomes for the superfamilies F-box and NB-ARC, and five additional families： the Aspartic proteases, BTB/POZ proteins （BTB）, Glutaredoxins, Trypsin a-amylase inhibitor proteins, and Zf-Dof proteins. Their evolutionary dynamic was investigated to understand how and why such important size variations are observed between these closely related species. We show that expansions resulted from both amplification, largely by tandem duplications, and contraction by gene losses. For the F-box and NB-ARC gene families, the genes conserved in all species were under strong purifying selection while expanded orthologous genes were under more relaxed purifying selection. In F-box, NB-ARC, and BTB, the expanded groups were enriched in genes with little evidence of expression, in comparison with conserved groups. We also detected 87 loci under positive selection in the expanded groups. These results show that most of the duplicated copies in the expanded groups evolve neutrally after duplication because of functional redundancy but a fraction of these genes were preserved following neofunctionalization. Hence, the lineage-specific expansions observed between Oryza species were partly driven by directional selection.     

DNA聚合酶x家族的系统发育分析

随着DNA聚合酶x家族成员数量的增加,家族内部的系统发育需要重新检查,来自病毒和细胞的DNA聚合酶x家族成员顺序第一次被汇编在一起,进行系统发育分析。分析显示：真核生物DNA聚合酶beta(polβ)可能起源于病毒基因的水平转移;DNA聚合酶mu(polμ)基因仅存在于哺乳动物基因中,是脱氧核苷酸末端转移酶（TdT）的重复基因;DNA聚合酶lambda(polλ)可能是polμ和TdT的祖先基因,但在某些物种的进化过程中发生了基因丢失。     

The evolutionary history of quorum-sensing systems in bacteria

Communication among bacterial cells through quorum-sensing (QS) systems is used to regulate ecologically and medically important traits, including virulence to hosts. QS is widespread in bacteria; it has been demonstrated experimentally in diverse phylogenetic groups, and homologs to the implicated genes have been discovered in a large proportion of sequenced bacterial genomes. The widespread distribution of the underlying gene families (LuxI/R and LuxS) raises the questions of how often QS genes have been transferred among bacterial lineages and the extent to which genes in the same QS system exchange partners or coevolve. Phylogenetic analyses of the relevant gene families show that the genes annotated as LuxI/R inducer and receptor elements comprise two families with virtually no homology between them and with one family restricted to the gamma-Proteobacteria and the other more widely distributed. Within bacterial phyla, trees for the LuxS and the two LuxI/R families show broad agreement with the ribosomal RNA tree, suggesting that these systems have been continually present during the evolution of groups such as the Proteobacteria and the Firmicutes. However, lateral transfer can be inferred for some genes (e.g., from Firmicutes to some distantly related lineages for LuxS). In general, the inducer/receptor elements in the LuxI/R systems have evolved together with little exchange of partners, although loss or replacement of partners has occurred in several lineages of gamma-Proteobacteria, the group for which sampling is most intensive in current databases. For instance, in Pseudomonas aeruginosa, a transferred QS system has been incorporated into the pathway of a native one. Gene phylogenies for the main LuxI/R family in Pseudomonas species imply a complex history of lateral transfer, ancestral duplication, and gene loss within the genus.     

Molecular evolution of duplicate copies of genes encoding cytosolic glutamine synthetase in Pisum sativum

Here, we describe two nearly identical expressed genes for cytosolic glutamine synthetase (GS3A and GS3B) in Pisum sativum L. RFLP mapping data indicates that the GS3A and GS3B genes are separate loci located on different chromosomes. DNA sequencing of the GS3A and GS3B genes revealed that the coding regions are 99% identical with only simple nucleotide substitutions resulting in three amino acid differences. Surprisingly, the non-coding regions (5 non-coding leader, the 11 introns, and 3 non-coding tail) all showed a high degree of identity (96%). In these non-coding regions, 25% of the observed differences between the GS3A and GS3B genes were deletions or duplications. The single difference in the 3 non-coding regions of the GS3A and GS3B genes was a 25 bp duplication of an AU-rich element in the GS3B gene. As the GS3B mRNA accumulates to lower levels than the GS3A gene, we tested whether this sequence which resembles an mRNA instability determinant functioned as such in the context of the GS mRNA. Using the GS3B 3 tail as part of a chimeric gene in transgenic plants, we showed that this AU-rich sequence has little effect on transgene mRNA levels. To determine whether the GS3A/GS3B genes represent a recent duplication, we examined GS3-like genes in genomic DNA of ancient relatives of P. sativum. We observed that several members of the Viceae each contain two genomic DNA fragments homologous to the GS3B gene, suggesting that this is an ancient duplication event. Gene conversion has been invoked as a possible mechanism for maintaining the high level of nucleotide similarity found between the GS3A and GS3B genes. Possible evolutionary reasons for the maintenance of these twin GS genes in pea, and the general duplication of genes for cytosolic GS in all plant species are discussed.     

How Many Sirtuin Genes Are Out There? Evolution of Sirtuin Genes in Vertebrates With a Description of a New Family Member

Studying the evolutionary history of gene families is a challenging and exciting task with a wide range of implications. In addition to exploring fundamental questions about the origin and evolution of genes, disentangling their evolution is also critical to those who do functional/structural studies to allow a deeper and more precise interpretation of their results in an evolutionary context. The sirtuin gene family is a group of genes that are involved in a variety of biological functions mostly related to aging. Their duplicative history is an open question, as well as the definition of the repertoire of sirtuin genes among vertebrates. Our results show a well-resolved phylogeny that represents an improvement in our understanding of the duplicative history of the sirtuin gene family. We identified a new sirtuin gene family member (SIRT3.2) that was apparently lost in the last common ancestor of amniotes but retained in all other groups of jawed vertebrates. According to our experimental analyses, elephant shark SIRT3.2 protein is located in mitochondria, the overexpression of which leads to an increase in cellular levels of ATP. Moreover, in vitro analysis demonstrated that it has deacetylase activity being modulated in a similar way to mammalian SIRT3. Our results indicate that there are at least eight sirtuin paralogs among vertebrates and that all of them can be traced back to the last common ancestor of the group that existed between 676 and 615 millions of years ago.     

DNA聚合酶X家族的起源与进化分析

随着DNA聚合酶X家族成员数量的增加,家族内部的系统发育需要重新检查。来自病毒和细胞的DNA聚合酶X家族成员序列第一次被汇编在一起,进行系统发育分析。分析显示：真核生物DNA聚合酶bcta(polβ)是这个家族的祖先基因,可能与昆虫痘病毒(EPv)之间发生过基因的水平转移;DNA聚合酶mu(polμ)基因仅存在于哺乳动物基因组中,是脱氧核苦酸末端转移酶(TdT)的重复基因;这个家族在低等真核生物的种系进化过程中发生了基因丢失。     

CVNH 结构域进化分析及选择压力检测

蓝藻抗病毒蛋白-N(Cyanovirin-N,CV-N)具有广谱抗病毒活性;其同源物构成 CVNH 蛋白家族,并且家族成员的抗人类免疫缺陷病毒结构域在进化上非常保守。本研究通过重建基因树对 CVNH 结构域的“零散分布”特点作了更为细致的了解,发现在黑曲霉、费氏曲菌、产黄青霉、粗糙脉孢霉、蓝杆藻和水蕨等物种中该结构域存在多份拷贝。在此基础上,分别采用机理式模型和 MEC 模型对 CVNH 结构域序列位点进行适应性进化分析,结果显示：（1）两类模型均未检测到统计上显著的正选择位点;（2）净化选择对 CVNH 起主导作用;（3）MEC 模型更适合所研究数据。进一步使用“支-特异”模型和“支-位点”模型对蓝杆菌菌株7822和7424的祖先分支进行检测,发现该分支经历过适应性进化,并且鉴定出6 个正选择位点(34L、63L、13H、76C、78K 和 80I)。这些结果对后续的 CVNH 功能验证和借助基因工程手段改良蛋白的抗病毒活性具重要意义。     

Evolutionary change of the numbers of homeobox genes in bilateral animals

It has been known that the conservation or diversity of homeobox genes is responsible for the similarity and variability of some of the morphological or physiological characters among different organisms. To gain some insights into the evolutionary pattern of homeobox genes in bilateral animals, we studied the change of the numbers of these genes during the evolution of bilateral animals. We analyzed 2,031 homeodomain sequences compiled from 11 species of bilateral animals ranging from Caenorhabditis elegans to humans. Our phylogenetic analysis using a modified reconciled-tree method suggested that there were at least about 88 homeobox genes in the common ancestor of bilateral animals. About 50-60 genes of them have left at least one descendant gene in each of the 11 species studied, suggesting that about 30-40 genes were lost in a lineage-specific manner. Although similar numbers of ancestral genes have survived in each species, vertebrate lineages gained many more genes by duplication than invertebrate lineages, resulting in more than 200 homeobox genes in vertebrates and about 100 in invertebrates. After these gene duplications, a substantial number of old duplicate genes have also been lost in each lineage. Because many old duplicate genes were lost, it is likely that lost genes had already been differentiated from other groups of genes at the time of gene loss. We conclude that both gain and loss of homeobox genes were important for the evolutionary change of phenotypic characters in bilateral animals.     

The alphaD-globin gene originated via duplication of an embryonic alpha-like globin gene in the ancestor of tetrapod vertebrates

Gene duplication is thought to play an important role in the co-option of existing protein functions to new physiological pathways. The globin superfamily of genes provides an excellent example of the kind of physiological versatility that can be attained through the functional and regulatory divergence of duplicated genes that encode different subunit polypeptides of the tetrameric hemoglobin protein. In contrast to prevailing views about the evolutionary history of the alpha-globin gene family, here we present phylogenetic evidence that the alpha(A)- and alpha(D)-globin genes are not the product of a single, tandem duplication of an ancestral globin gene with adult function in the common ancestor of extant birds, reptiles, and mammals. Instead, our analysis reveals that the alpha(D)-globin gene of amniote vertebrates arose via duplication of an embryonic alpha-like globin gene that predated the radiation of tetrapods. The important evolutionary implication is that the distinct biochemical properties of alpha(D)-hemoglobin (HbD) are not exclusively derived characters that can be attributed to a post-duplication process of neofunctionalization. Rather, many of the distinct biochemical properties of HbD are retained ancestral characters that reflect the fact that the alpha(D)-globin gene arose via duplication of a gene that had a larval/embryonic function. These insights into the evolutionary origin of HbD illustrate how adaptive modifications of physiological pathways may result from the retention and opportunistic co-option of ancestral protein functions.