The life and death of gene families

One of the unique insights provided by the growing number of fully sequenced genomes is the pervasiveness of gene duplication and gene loss. Indeed, several metrics now suggest that rates of gene birth and death per gene are only 10–40% lower than nucleotide substitutions per site, and that per nucleotide, the consequent lineage‐specific expansion and contraction of gene families may play at least as large a role in adaptation as changes in orthologous sequences. While gene family evolution is pervasive, it may be especially important in our own evolution since it appears that the “revolving door” of gene duplication and loss has undergone multiple accelerations in the lineage leading to humans. In this paper, we review current understanding of gene family evolution including: methods for inferring copy number change, evidence for adaptive expansion and adaptive contraction of gene families, the origins of new families and deaths of previously established ones, and finally we conclude with a perspective on challenges and promising directions for future research.     

大豆蛋白编码基因起源与进化

物种基因组成是一个高度动态的进化过程, 其中相对较近起源的种系和物种特异性基因会持续整合到包含古老基因的原始基因网络中。新基因在塑造基因组结构中发挥重要作用, 能提高物种适应性。基因复制和新基因的从头起源是产生新基因及改变基因家族大小的2种方式。目前, 大豆(Glycine max)基因起源时间与进化模式的相互联系很大程度上还未被探索。该研究选择19种具有代表性的被子植物基因组, 分析基因含量动态性与大豆基因起源之间的潜在联系。采用基因出现法, 研究显示约58.7%的大豆基因能追溯到大约1.5亿年前, 同时有21.7%的基因为最近起源的orphan基因。研究结果表明, 与新基因相比, 古老基因受到更强的负选择压并且更加保守。此外, 古老基因的表达水平更高且更可能发生选择性剪切。此外, 具有不同拷贝数的基因在上述特征中也具有明显差异。研究结果有助于认识不同年龄基因的进化模式。     

大豆蛋白编码基因起源与进化

物种基因组成是一个高度动态的进化过程, 其中相对较近起源的种系和物种特异性基因会持续整合到包含古老基因的原始基因网络中。新基因在塑造基因组结构中发挥重要作用, 能提高物种适应性。基因复制和新基因的从头起源是产生新基因及改变基因家族大小的2种方式。目前, 大豆(Glycine max)基因起源时间与进化模式的相互联系很大程度上还未被探索。该研究选择19种具有代表性的被子植物基因组, 分析基因含量动态性与大豆基因起源之间的潜在联系。采用基因出现法, 研究显示约58.7%的大豆基因能追溯到大约1.5亿年前, 同时有21.7%的基因为最近起源的orphan基因。研究结果表明, 与新基因相比, 古老基因受到更强的负选择压并且更加保守。此外, 古老基因的表达水平更高且更可能发生选择性剪切。此外, 具有不同拷贝数的基因在上述特征中也具有明显差异。研究结果有助于认识不同年龄基因的进化模式。     

Evolution of nodal and nodal‐related genes and the putative composition of the heterodimers that trigger the nodal pathway in vertebrates

Nodal is a signaling molecule that belongs to the transforming growth factor‐β superfamily that plays key roles during the early stages of development of animals. In vertebrates Nodal forms an heterodimer with a GDF1/3 protein to activate the Nodal pathway. Vertebrates have a paralog of nodal in their genomes labeled Nodal‐related, but the evolutionary history of these genes is a matter of debate, mainly because of the presence of a variable numbers of genes in the vertebrate genomes sequenced so far. Thus, the goal of this study was to investigate the evolutionary history of the Nodal and Nodal‐related genes with an emphasis in tracking changes in the number of genes among vertebrates. Our results show the presence of two gene lineages (Nodal and Nodal‐related) that can be traced back to the ancestor of jawed vertebrates. These lineages have undergone processes of differential retention and lineage‐specific expansions. Our results imply that Nodal and Nodal‐related duplicated at the latest in the ancestor of gnathostomes, and they still retain a significant level of functional redundancy. By comparing the evolution of the Nodal/Nodal‐related with GDF1/3 gene family, it is possible to infer that there are several types of heterodimers that can trigger the Nodal pathway among vertebrates.     

Origins, lineage-specific expansions, and multiple losses of tyrosine kinases in eukaryotes

Tyrosine kinases are important components of metazoan signaling pathways, and their mutant forms are implicated in various malignancies. Searching the sequences from the genomes of 28 eukaryotes and the GenBank, we found tyrosine kinases not only in metazoans but also in the green algae Chlamydomonas reinhardtii, the potato late blight pathogen Phytophthora infestans, and the protozoan pathogen Entamoeba histolytica, contrary to the current view that tyrosine kinases are animal-specific. Based on a phylogenetic analysis, we divided this gene family into 43 subfamilies and found that at least 19 tyrosine kinases were likely present in the common ancestor of chordates, arthropods, and nematodes. Interestingly, most of the subfamilies have conserved domain organizations among subfamily members but have undergone different degrees of expansion during the evolution of metazoans. In particular, a large number of duplications occurred in the lineage leading to the common ancestor of Tagifugu and mammals after its split from the Ciona lineage about 450 to 550 MYA. The timing of expansion coincides with proposed large-scale duplication event in the chordate lineage. Furthermore, gene losses have occurred in most subfamilies. Interestingly, different subfamilies have similar net gain rates in the chordates studied. However, the tyrosine kinases in mouse and human or in fruit fly and mosquito mostly have a one-to-one relationship between species, indicating that static periods of 90 Myr or longer in tyrosine kinase evolution have followed large expansion events.     

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。     

Rapid rates of lineage-specific gene duplication and deletion in the alpha-globin gene family

Phylogeny reconstructions of the globin gene families have revealed that paralogous genes within species are often more similar to one another than they are to their orthologous counterparts in closely related species. This pattern has been previously attributed to mechanisms of concerted evolution such as interparalog gene conversion that homogenize sequence variation between tandemly duplicated genes and therefore create the appearance of recent common ancestry. Here we report a comparative genomic analysis of the alpha-globin gene family in mammals that reveal a surprisingly high rate of lineage-specific gene duplication and deletion via unequal crossing-over. Results of our analysis reveal that patterns of sequence similarity between paralogous alpha-like globin genes from the same species are only partly explained by concerted evolution between preexisting gene duplicates. In a number of cases, sequence similarity between paralogous sequences from the same species is attributable to recent ancestry between the products of de novo gene duplications. As a result of this surprisingly rapid rate of gene gain and loss, many mammals possess alpha-like globin genes that have no orthologous counterparts in closely related species. The resultant variation in gene copy number among species may represent an important source of regulatory variation that affects physiologically important aspects of blood oxygen transport and aerobic energy metabolism.     

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.     

一种新的基因注释语义相似度计算方法

基因本体(GO)数据库为基因提供了统一的注释,有效地解决了不同数据库描述相同基因的不一致问题。但是,根据基因注释如何比较基因的功能相似性,这个问题仍然没有得到有效解决。本文提出一种新的基因注释语义相似度计算方法,这种方法在本质上是基于基因的生物学特性,其特点在于结点的语义相似度与结点所在集合无关,只与结点在GO图的位置有关,语义相似度可被重复利用。它既考虑了基因所映射的GO结点深度,又考虑了两GO结点之间所有路径对结点语义相似度的影响。文中以酵母菌的异亮氨酸降解代谢通路和谷氨酸合成代谢通路为实验,实验结果表明这种算法能准确地计算基因注释语义相似度。     

Recurrent gene loss correlates with the evolution of stomach phenotypes in gnathostome history

The stomach, a hallmark of gnathostome evolution, represents a unique anatomical innovation characterized by the presence of acid- and pepsin-secreting glands. However, the occurrence of these glands in gnathostome species is not universal; in the nineteenth century the French zoologist Cuvier first noted that some teleosts lacked a stomach. Strikingly, Holocephali (chimaeras), dipnoids (lungfish) and monotremes (egg-laying mammals) also lack acid secretion and a gastric cellular phenotype. Here, we test the hypothesis that loss of the gastric phenotype is correlated with the loss of key gastric genes. We investigated species from all the main gnathostome lineages and show the specific contribution of gene loss to the widespread distribution of the agastric condition. We establish that the stomach loss correlates with the persistent and complete absence of the gastric function gene kit—H⁺/K⁺-ATPase (Atp4A and Atp4B) and pepsinogens (Pga, Pgc, Cym)—in the analysed species. We also find that in gastric species the pepsinogen gene complement varies significantly (e.g. two to four in teleosts and tens in some mammals) with multiple events of pseudogenization identified in various lineages. We propose that relaxation of purifying selection in pepsinogen genes and possibly proton pump genes in response to dietary changes led to the numerous independent events of stomach loss in gnathostome history. Significantly, the absence of the gastric genes predicts that reinvention of the stomach in agastric lineages would be highly improbable, in line with Dollo''s principle.     

草菇GH61家族基因的生物信息学分析及金属离子对其表达水平的影响

在前期工作中发现草菇含有30个GH61家族基因同源物（Vv_gh61_1至Vv_gh61_30）,进一步分析了这些基因的结构特点以及其编码蛋白基本性质和系统进化关系,并研究了Cu2+和Mn2+对基因表达水平的影响。分析表明有17个草菇GH61基因串联成6个基因簇,存在明显的串联重复现象,系统发育树与基因外显子位置分析表明串联重复基因分布在同一进化分枝上并具有相似的基因结构,串联重复基因编码序列一致性在71%–94%之间。草菇GH61编码蛋白的氨基酸数目在217–442aa之间,分子量和等电点分别介于22.4–45.4kDa和5.2–9.3之间,绝大多数都含有信号肽并定位在细胞外,都含有Glyco_hydro_61功能域以及CBM1、peroxidase等多样化的功能域,系统进化树表明草菇GH61家族基因具有3个主要进化分枝,与灰盖鬼伞等的GH61基因有较近的进化关系。金属离子诱导作用显示,Mn2+对草菇GH61家族基因的表达水平存在诱导作用而Cu2+的诱导作用不明显。     

On the nature of gene innovation: duplication patterns in microbial genomes

Gene duplication is considered a major force in gene family expansion and gene innovation. As gene copies assume novel functions, they must avoid periods of neutrality or be deleted from the genome. Current opinions state that copies avoid neutrality through gene dosage effects. These copies are therefore selected from an early stage. This study concentrates on the flow of copies from recent duplication to gene innovation. We have studied 21 microbial genomes using amino acid divergence to describe paralog evolution in the long-term perspective. Five of these were studied in closer detail using nucleotide divergence for a shorter perspective. It was found that rates of duplication and deletion are high, with only a small fraction of duplications retained and apparently selected. This leads to a steady accumulation of paralogs, which seems to be of a similar magnitude in most of the genomes. Furthermore, it is found that genes of high expression level, as measured by their codon bias, are strongly underrepresented among the most recent duplications. Based on these and other observations, it is suggested that gene innovation is driven by amplification of weak, ancillary functions rather than strong, established functions.