Evolution of a Hypervariable Region of the Low Density Lipoprotein Receptor (LDLR) Gene in Humans and other Hominoids

Alu repeats in primates have been shown to evolve at a neutral mutation rate, as anticipated for non-coding autosomal loci. However, we have identified Alu elements within the 3' untranslated region (UTR) of the low density lipoprotein receptor (LDLR) gene that exhibited highly accelerated rates of evolution. In humans, a 100- and 25-fold increase in average divergence, for an upstream Alu (Alu U) and a downstream Alu (Alu D) respectively, was estimated based on sequence analysis among eight individuals of diverse ethnic backgrounds. None of these individuals demonstrated identical sequences within a 950 base region consisting of these two Alu elements. The hypervariability of this genetic region in the nuclear genome yields a potentially powerful tool for human population studies, forensics and paternity. Additionally, the mutation rate of Alu U among non-human hominoids was also accelerated, although to a lesser extent of roughly 3-fold that of other Alu elements. Sequence analysis of various Hominoidea species demonstrated its utility as a phylogenetic tool. The mechanism for the hypervariability in mutation rates is unclear, but may be accelerated as a result of Alu-mediated gene conversion in the human lineage.     

植物WUSCHEL-related homeobox (WOX) 家族研究进展

WUSCHEL相关的同源异型盒(WUSCHEL-related homeobox,WOX)转录因子家族,在植物发育的众多阶段(茎和根顶端分生区的建成、侧生器官的发育、花器官的形成和胚的发育),尤其是在细胞增殖和分化较为旺盛的区域发挥重要的调控作用,即促进细胞的增殖或抑制细胞的分化。就WOX同源异型盒转录因子家族的系统进化分析、WOX家族成员的分子特征、WOX基因的生物学功能及其作用机制进行综述,并对本领域未来的发展方向作出展望。     

Evolution of the Hedgehog Gene Family

Effective intercellular communication is an important feature in the development of multicellular organisms. Secreted hedgehog (hh) protein is essential for both long- and short-range cellular signaling required for body pattern formation in animals. In a molecular evolutionary study, we find that the vertebrate homologs of the Drosophila hh gene arose by two gene duplications: the first gave rise to Desert hh, whereas the second produced the Indian and Sonic hh genes. Both duplications occurred before the emergence of vertebrates and probably before the evolution of chordates. The amino-terminal fragment of the hh precursor, crucial in long- and short-range intercellular communication, evolves two to four times slower than the carboxyl-terminal fragment in both Drosophila hh and its vertebrate homologues, suggesting conservation of mechanism of hh action in animals. A majority of amino acid substitutions in the amino- and carboxyl-terminal fragments are conservative, but the carboxyl-terminal domain has undergone extensive insertion-deletion events while maintaining its autocleavage protease activity. Our results point to similarity of evolutionary constraints among sites of Drosophila and vertebrate hh homologs and suggest some future directions for understanding the role of hh genes in the evolution of developmental complexity in animals.     

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.     

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。     

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.     

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.     

山茶属CHS基因家族的组成和分子进化初探

用PCR方法从4种山茶属(Camellia)(山茶科)(Theaceae)植物的总DNA中分别扩增到CHS基因外显子2的部分序列,经克隆、测序得到16个该基因的序列,这些序列与来自GenBank的该属另一种植物的3个序列及作为外类群的大豆(Glycine max (L.) Merr.)的2个序列一起进行分析.研究表明,山茶属CHS基因家族在进化过程中已分化为A、B、C三个亚家族,包括A1、A2、A3、B1、B2、C 等6类不同的基因成员;其中只有A2类成员为全部被研究的5种植物所共有,而其他5类成员只在部分被研究的植物中发现;所有这些CHS成员具有很高的同源性:在核苷酸水平上同一亚家族内基本上高于90%,不同亚家族间也在78%以上.从推测的氨基酸组成看,山茶属内CHS基因的功能已发生了分化,各类成员的碱基替代率有较大差异; 从分子系统发育树和可能的氨基酸组成分析,山茶属具有新功能的基因成员是在经过基因重复后,或是由少数几个位点的突变而成,或是由逐渐积累的突变而形成的.进一步分析认为,该属CHS基因的分化直到近期还在活跃地进行,并且不同种的进化式样有一定的差别,这种不同的进化式样可能是物种形成后受不同环境因素影响而形成的.     

山茶属CHS基因家族的组成和分子进化初探

用PCR方法从4种山茶属(Camellia)(山茶科)(Tlaeaceae)植物的总DNA中分别扩增到CHS基因外显子2的部分序列,经克隆、测序得到16个该基因的序列,这些序列与来自GenBank的该属另一种植物的3个序列及作为外类群的大豆(Glycine max (L)Merr)的2个序列一起进行分析。研究表明,山茶属CHS基因家族在进化过程中已分化为A、B、c三个亚家族,包括A1、A2、A3、B1、B2、C等6类不同的基因成员;其中只有A2类成员为全部被研究的5种植物所共有,而其他5类成员只在部分被研究的植物中发现;所有这些CHS成员具有很高的同源性：在核苷酸水平上同一亚家族内基本上高于90％,不同亚家族间也在78％以上。从推测的氨基酸组成看,山茶属内CHS基因的功能已发生了分化,各类成员的碱基替代率有较大差异;从分子系统发育树和可能的氨基酸组成分析,山茶属具有新功能的基因成员是在经过基因重复后,或是由少数几个位点的突变而成,或是由逐渐积累的突变而形成的。进一步分析认为,该属CHS基因的分化直到近期还在活跃地进行,并且不同种的进化式样有一定的差别,这种不同的进化式样可能是物种形成后受不同环境因素影响而形成的。