Evolution of the Vertebrate Resistin Gene Family

Resistin (encoded by Retn) was previously identified in rodents as a hormone associated with diabetes; however human resistin is instead linked to inflammation. Resistin is a member of a small gene family that includes the resistin-like peptides (encoded by Retnl genes) in mammals. Genomic searches of available genome sequences of diverse vertebrates and phylogenetic analyses were conducted to determine the size and origin of the resistin-like gene family. Genes encoding peptides similar to resistin were found in Mammalia, Sauria, Amphibia, and Actinistia (coelacanth, a lobe-finned fish), but not in Aves or fish from Actinopterygii, Chondrichthyes, or Agnatha. Retnl originated by duplication and transposition from Retn on the early mammalian lineage after divergence of the platypus, but before the placental and marsupial mammal divergence. The resistin-like gene family illustrates an instance where the locus of origin of duplicated genes can be identified, with Retn continuing to reside at this location. Mammalian species typically have a single copy Retn gene, but are much more variable in their numbers of Retnl genes, ranging from 0 to 9. Since Retn is located at the locus of origin, thus likely retained the ancestral expression pattern, largely maintained its copy number, and did not display accelerated evolution, we suggest that it is more likely to have maintained an ancestral function, while Retnl, which transposed to a new location, displays accelerated evolution, and shows greater variability in gene number, including gene loss, likely evolved new, but potentially lineage-specific, functions.     

Evolution of the Growth Hormone Gene Family

SYNOPSIS. Growth hormone, prolactin and chorionic somatomammotropin(placental lactogen) area family of hormones that are relatedby function, immunochemistry and structure. Because of the structuralsimilarities between these hormones, it was proposed that thecorresponding genes were derived from a common precursor geneby duplication and sequence divergence. Comparisons of the mRNAsequences and chromosomal genes for these hormones from severalspecies provide additional support for the model of their commonancestry and indications of how the precursor genewas formed.The diversification of these three genes has involved changesin codon choices thataffect the overall G-C content of the genes,alterations in the sizes of introns with conservedexon-intronboundaries and concerted evolutionary mechanisms with duplicatedgrowth hormone andhorionic somatomammotropin genes in humans.The precursor gene appears to have evolved by the fourfold duplicationof one exon element and the separate insertion of an exon encodinga different protein domain. Finally, there also appears to havebeen the separate insertion of sequences containing a promoterelement and a potential glucocorticoid regulatory element.     

Evolutionary Genomics and Adaptive Evolution of the Hedgehog Gene Family (Shh,Ihh and Dhh) in Vertebrates

The Hedgehog (Hh) gene family codes for a class of secreted proteins composed of two active domains that act as signalling molecules during embryo development, namely for the development of the nervous and skeletal systems and the formation of the testis cord. While only one Hh gene is found typically in invertebrate genomes, most vertebrates species have three (Sonic hedgehog – Shh; Indian hedgehog – Ihh; and Desert hedgehog – Dhh), each with different expression patterns and functions, which likely helped promote the increasing complexity of vertebrates and their successful diversification. In this study, we used comparative genomic and adaptive evolutionary analyses to characterize the evolution of the Hh genes in vertebrates following the two major whole genome duplication (WGD) events. To overcome the lack of Hh-coding sequences on avian publicly available databases, we used an extensive dataset of 45 avian and three non-avian reptilian genomes to show that birds have all three Hh paralogs. We find suggestions that following the WGD events, vertebrate Hh paralogous genes evolved independently within similar linkage groups and under different evolutionary rates, especially within the catalytic domain. The structural regions around the ion-binding site were identified to be under positive selection in the signaling domain. These findings contrast with those observed in invertebrates, where different lineages that experienced gene duplication retained similar selective constraints in the Hh orthologs. Our results provide new insights on the evolutionary history of the Hh gene family, the functional roles of these paralogs in vertebrate species, and on the location of mutational hotspots.     

Evolution of the Metazoan-Specific Importin α Gene Family

Importin αs are import receptors for nuclear localization signal-containing proteins. Most animal importin αs assort into α1, α2, and α3 groups. Studies in Drosophila melanogaster, Caenorhabditis elegans, and mouse suggest that the animal importin α gene family evolved from ancestral plant-like genes to serve paralog-specific roles in gametogenesis. To explore this hypothesis we extended the phylogenetic analysis of the importin α gene family to nonbilateral animals and investigated whether animal-like genes occur in premetazoan taxa. Maximum likelihood analysis suggests that animal-like importin α genes occur in the Choanoflaggelate Monosiga brevicollis and the amoebozoan Dictyostelium; however, both of these results are caused by long-branch attraction effects. The absence of animal-like α genes in premetazoan taxa is consistent with the hypothesis that they duplicated and then specialized to function in animal gametogenesis. The gene structures of the importin αs provide insight into how the animal importin α gene family may have evolved from the most likely ancestral gene. Interestingly, animal α1s are more similar to plant and fungal α1-like sequences than they are to animal α2s or α3s. We show that animal α1 genes share most of their introns with plant α1-like genes, and α2s and α3s share many more intron positions with each other than with the α1s. Together, phylogenetics and gene structure analysis suggests a parsimonious path for the evolution of the mammalian importin α gene family from an ancestral α1-like progenitor. Finally, these results establish a rational basis for a unified nomenclature of the importin α gene family.     

Unc5基因家族多样性进化的研究

Uncoordinated-5(Unc5)基因家族属于经典的轴突导向基因家族。为了探讨Unc5的进化和分化规律,首先通过序列比对和蛋白质结构预测鉴定了Unc5基因家族成员的起源和分布,再利用PAML和DIVERGE软件分析了各基因亚型的进化选择压力和功能歧化。结果表明,Unc5基因家族在脊椎动物中受到了不同程度的选择压力,其中Unc5C基因型受到了纯化选择作用,而Unc5A、Unc5B和Unc5D基因型受到了正选择作用,并且在这3个基因型中分别检测到了8个、1个和6个正选择位点。此外,DIVERGE软件检测出38个I型功能歧化位点和97个Ⅱ型功能歧化位点。这些正选择位点和功能分歧位点为进一步研究Unc5蛋白的结构和功能提供了参考和依据。     

miR-34基因家族的分子进化

根据miRNA基因在进化中高度保守的特点,利用生物信息学方法在目前已测序的动物物种中搜寻参与哺乳动物早期发育调控的mir-34基因的同源序列,在33个不同的动物物种中获得了miR-34基因的54条同源序列,其中18条为新发现的序列。表明miR-34是高度保守的,广泛存在于后生动物中。目前发现的mir-34基因80%位于基因间隔区,少数位于蛋白编码基因的内含子区和3′UTR上。不同动物中,mir-34基因成熟序列的同源性为68%,前体序列为38.89%。在无脊椎动物中只有一个mir-34,而在几乎所有的脊椎动物中都有mir-34a,mir-34b,mir-34c,形成miR-34基因家族。系统进化分析表明,脊椎动物中miR-34基因家族是通过基因的串联和局部重复形成的,这个过程中伴随着个别碱基的变异。     

Molecular Evolution of the Plant R Regulatory Gene Family

Anthocyanin pigmentation patterns in different plant species are controlled in part by members of the myc-like R regulatory gene family. We have examined the molecular evolution of this gene family in seven plant species. Three regions of the R protein show sequence conservation between monocot and dicot R genes. These regions encode the basic helix-loop-helix domain, as well as conserved N-terminal and C-terminal domains; mean replacement rates for these conserved regions are 1.02 X 10(-9) nonsynonymous nucleotide substitutions per site per year. More than one-half of the protein, however, is diverging rapidly, with nonsynonymous substitution rates of 4.08 X 10(-9) substitutions per site per year. Detailed analysis of R homologs within the grasses (Poaceae) confirm that these variable regions are indeed evolving faster than the flanking conserved domains. Both nucleotide substitutions and small insertion/deletions contribute to the diversification of the variable regions within these regulatory genes. These results demonstrate that large tracts of sequence in these regulatory loci are evolving at a fairly rapid rate.     

啮齿目泌乳刺激素基因家族的分子进化研究

在大鼠基因组数据库中搜索得到两个泌乳刺激素基因家族的新成员。进一步分析显示该基因家族起源于啮齿目和其他哺乳动物分歧之后,而且大部分基因座位的重排在大、小鼠分歧之前已经完成。但PL-Ⅰ和PL-Ⅱ基因簇却是例外,它们在基因树上以物种特异的方式聚类。结合基因转换的检验、染色体上相对位置比较和基因重复时间估计的结果,认为啮齿目PL-Ⅰ和PL-Ⅱ基因是物种特异的,它们由一系列在大、小鼠分歧之后发生的基因重复事件形成。结果还揭示了在啮齿目泌乳刺激素基因家族进化过程中持续不断的发生了基因重复和基因分化事件。     

Molecular Evolution of Prolactin Gene Family in Rodents

In this study, we identified two novel members of prolactin gene family in rat by blast searches against the published genomic database. A further analysis showed that gene duplications leading to PRL gene family in rodents occurred after rodents diverged from other mammals. Major reorganization of the gene loci in rodents was largely completed before the split of rat and mouse. But PL-I and PL-II genes are the exceptions, which have clustered in a species-specific manner in the phylogenetic tree. By combining results from gene conversion testing, relative chromosomal location comparison and estimated time for gene duplication, we believe that rodent PL-I and PL-II genes are species-specific and are the results of serial duplications which occurred after the divergence of mouse and rat. Our analysis also reveals that continual gene duplication and divergence occurred during the evolution of rodent PRL gene family.     

促葡萄糖转运蛋白基因家族的分子进化研究

葡萄糖转运蛋白是一个在结构上相似功能上不同的多基因家族（ＧＬＵＴ１－ＧＬＵＴ５）。由于这一组蛋白和体内的葡萄糖利用有关,因此被认为是糖尿病胰岛素抵抗（抗性）的一个候选基因。本文比较了不同种生物这一基因家族的氨基酸和核苷酸顺序;推测了亲水性和疏水性分布;计算了蛋白质和核苷酸的进化距离,并在此基础上构建了分子进化树。研究表明：这一基因家族具有高度的同源性、极为相似的亲水性和疏水性分布以及结构的对称性。提示这一基因家族起源于一个共同的祖先并可能通过基因的重复而形成。这一进化机制可能有利于氨基酸结构的稳定及抵抗突变的作用。由于邻元法构建的进化树其分支长度存在差异,提示在这一基因家族的进化过程中,各分支上的进化速率并不相同。蛋白质进化距离和核苷酸进化距离所构建进化树的差异提示了在基因组中可能存在隐匿替换。两种方法构建的进化树都提示了ＧＬＵＴ１、３、４在结构和功能上要更为保守。     

Multiple Inter-Kingdom Horizontal Gene Transfers in the Evolution of the Phosphoenolpyruvate Carboxylase Gene Family

Pepcase is a gene encoding phosphoenolpyruvate carboxylase that exists in bacteria, archaea and plants,playing an important role in plant metabolism and development. Most plants have two or more pepcase genes belonging to two gene sub-families, while only one gene exists in other organisms. Previous research categorized one plant pepcase gene as plant-type pepcase (PTPC) while the other as bacteria-type pepcase (BTPC) because of its similarity with the pepcase gene found in bacteria. Phylogenetic reconstruction showed that PTPC is the ancestral lineage of plant pepcase, and that all bacteria, protistpepcase and BTPC in plants are derived from a lineage of pepcase closely related with PTPC in algae. However, their phylogeny contradicts the species tree and traditional chronology of organism evolution. Because the diversification of bacteria occurred much earlier than the origin of plants, presumably all bacterialpepcase derived from the ancestral PTPC of algal plants after divergingfrom the ancestor of vascular plant PTPC. To solve this contradiction, we reconstructed the phylogeny of pepcase gene family. Our result showed that both PTPC and BTPC are derived from an ancestral lineage of gamma-proteobacteriapepcases, possibly via an ancient inter-kingdom horizontal gene transfer (HGT) from bacteria to the eukaryotic common ancestor of plants, protists and cellular slime mold. Our phylogenetic analysis also found 48other pepcase genes originated from inter-kingdom HGTs. These results imply that inter-kingdom HGTs played important roles in the evolution of the pepcase gene family and furthermore that HGTsare a more frequent evolutionary event than previouslythought.     

miR396基因家族的进化及功能分析

MicroRNA(miRNA)是由约22个核苷酸组成的内源性非编码小分子RNA,广泛存在于真核细胞中,通过与靶基因的互补配对在转录后水平对基因表达进行调控,导致mRNA的降解或翻译抑制。本文通过对目前miRBase中收录的miR396家族进行生物信息学分析发现,该家族在植物界中高度保守,它们可能起源于较为古老的物种,经历长期复杂的进化过程而保留了下来;靶基因预测结果显示生长调控因子GRF为其主要靶标;启动子分析表明, miR396编码基因的上游存在光、温度、激素、厌氧、干旱及病害等胁迫响应相关的顺式作用元件,它们可与转录因子结合,参与多种胁迫应答反应。本文可为全面深入研究miRNA的作用机制奠定基础。     

MIR166基因家族在陆生植物中的进化模式分析

MicroRNA（miRNA）是一类广泛存在于真核生物中的具有转录后水平调控功能的内源非编码小分子RNA。在植物中．miRNA通过对靶基因的剪切或沉默来实现对植物生命活动的调控,它是基因表达调控网络的重要组成部分。miR165／166（miR166）是陆生植物中最为古老的MIRNA家族之一,它通过对3型同源异域型-亮氨酸拉链（1id—ZIPⅢ）等靶标的调控,在植物的众多发育时期起着关键的调控作用。本文分析了MIR166基因在陆生植物中的进化关系,并对MIR166在基部陆生植物小立碗藓（Physcomitrella patens）中的复制及进化进行了研究。此外,HD—ZIPⅢ蛋白是植物中重要的一类转录因子,miR166对HD-ZIP Ⅲ基因的调控作用在陆地植物保守的存在,本文对HD—ZIP Ⅲ基因和miR166在进化中的相互作用进行了初步的探讨。     

Structure and Evolution of the Actin Gene Family in Arabidopsis Thaliana

Higher plants contain families of actin-encoding genes that are divergent and differentially expressed. Progress in understanding the functions and evolution of plant actins has been hindered by the large size of the actin gene families. In this study, we characterized the structure and evolution of the actin gene family in Arabidopsis thaliana. DNA blot analyses with gene-specific probes suggested that all 10 of the Arabidopsis actin gene family members have been isolated and established that Arabidopsis has a much simpler actin gene family than other plants that have been examined. Phylogenetic analyses suggested that the Arabidopsis gene family contains at least two ancient classes of genes that diverged early in land plant evolution and may have separated vegetative from reproductive actins. Subsequent divergence produced a total of six distinct subclasses of actin, and five showed a distinct pattern of tissue specific expression. The concordance of expression patterns with the phylogenetic structure is discussed. These subclasses appear to be evolving independently, as no evidence of gene conversion was found. The Arabidopsis actin proteins have an unusually large number of nonconservative amino acid substitutions, which mapped to the surface of the actin molecule, and should effect protein-protein interactions.     

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.     

Evolution of the F-Box Gene Family in Euarchontoglires: Gene Number Variation and Selection Patterns

F-box proteins are substrate adaptors used by the SKP1–CUL1–F-box protein (SCF) complex, a type of E3 ubiquitin ligase complex in the ubiquitin proteasome system (UPS). SCF-mediated ubiquitylation regulates proteolysis of hundreds of cellular proteins involved in key signaling and disease systems. However, our knowledge of the evolution of the F-box gene family in Euarchontoglires is limited. In the present study, 559 F-box genes and nine related pseudogenes were identified in eight genomes. Lineage-specific gene gain and loss events occurred during the evolution of Euarchontoglires, resulting in varying F-box gene numbers ranging from 66 to 81 among the eight species. Both tandem duplication and retrotransposition were found to have contributed to the increase of F-box gene number, whereas mutation in the F-box domain was the main mechanism responsible for reduction in the number of F-box genes, resulting in a balance of expansion and contraction in the F-box gene family. Thus, the Euarchontoglire F-box gene family evolved under a birth-and-death model. Signatures of positive selection were detected in substrate-recognizing domains of multiple F-box proteins, and adaptive changes played a role in evolution of the Euarchontoglire F-box gene family. In addition, single nucleotide polymorphism (SNP) distributions were found to be highly non-random among different regions of F-box genes in 1092 human individuals, with domain regions having a significantly lower number of non-synonymous SNPs.     

哺乳动物锌指蛋白家族中KRAB功能域的进化

KRAB锌指基因是哺乳动物中最大的转录调控因子家族,它的多数成员在基因组上成簇分布,具有五种不同的亚家族,在功能行使上承担着不同的作用。本文通过对人类、黑猩猩、小鼠、大鼠和狗五种哺乳动物全蛋白质组序列及mRNA组织表达谱分析,验证了C2H2锌指结构在单个KRAB蛋白质中出现的数目多于一般锌指蛋白质;KRAB功能域在各物种中分布显著不同且与分化时间不成正比,这表明KRAB相关功能域多样性在灵长类进化过程中潜在的适应性进化。同时,提出KRAB亚家族进化的路线：即KRAB—Aa为起始家族,Ba由Aa直接演变形成,而Ca,blonga和XRCC-Z种亚型可能经过Ba或直接从Aa演变形成;此外,锌指结构在单个蛋白质中出现个数伴随KRAB功能域自身的进化路线逐渐递增,反映了KRAB功能域在形成新转录调控因子方面的积极作用。     

miR-124基因家族的分子进化与靶基因预测

MicroRNA (miRNA)是一类内源基因编码的长度约22个核苷酸的非编码单链RNA分子.依据其在进化中高度保守的特点,利用生物信息学方法在目前已测序的物种中搜寻在哺乳动物中枢神经系统特异表达的miR-124基因的同源序列.在80个不同的动物物种中找到了150条miR-124基因的同源序列,其中27条为新发现的序列.目前发现的miR-124基因中,除线虫cel-mir-124和小鼠mmu-mir-124-2位于内含子之外,其他均位于基因间隔区.不同物种中,miR-124基因成熟序列的相似性为89.54％,前体序列为41.98％.miR-124基因在大多数无脊椎动物中为单拷贝,而在脊椎动物中大多为多拷贝,表明从无脊推动物到脊椎动物进化过程中miR-124基因发生了重复.靶基因预测结果显示,在人、小鼠和大鼠等哺乳动物中mir-124大多靶位点也是保守的.