哺乳动物系统发育基因组学研究进展

哺乳动物是一类最进化并在地球上占主导地位的动物类群,重建其系统发育关系一直是分子系统学的研究热点。随着越来越多物种全基因组测序的完成,在基因组水平上探讨该类动物的系统发育关系与进化成为研究的热点。本文从全基因组序列,稀有基因组变异及染色体涂染等几个方面简要介绍了当前系统发育基因组学在现生哺乳动物分子系统学中的应用,综合已有的研究归纳整理了胎盘亚纲的总目及目间的系统发育关系,给出了胎盘动物19 个目的系统发育树。本文还分析了哺乳动物系统发育基因组学目前所面临的主要问题及未来的发展前景。     

Housekeeping genes for phylogenetic analysis of eutherian relationships

The molecular relationship of placental mammals has attracted great interest in recent years. However, 2 crucial and conflicting hypotheses remain, one with respect to the position of the root of the eutherian tree and the other the relationship between the orders Rodentia, Lagomorpha (rabbits, hares), and Primates. Although most mitochondrial (mt) analyses have suggested that rodents have a basal position in the eutherian tree, some nuclear data in combination with mt-rRNA genes have placed the root on the so-called African clade or on a branch that includes this clade and the Xenarthra (e.g., anteater and armadillo). In order to generate a new and independent set of molecular data for phylogenetic analysis, we have established cDNA sequences from different tissues of various mammalian species. With this in mind, we have identified and sequenced 8 housekeeping genes with moderately fast rate of evolution from 22 placental mammals, representing 11 orders. In order to determine the root of the eutherian tree, the same genes were also sequenced for 3 marsupial species, which were used as outgroup. Inconsistent with the analyses of nuclear + mt-rRNA gene data, the current data set did not favor a basal position of the African clade or Xenarthra in the eutherian tree. Similarly, by joining rodents and lagomorphs on the same basal branch (Glires hypothesis), the data set is also inconsistent with the tree commonly favored in mtDNA analyses. The analyses of the currently established sequences have helped examination of problematic parts in the eutherian tree at the same time as they caution against suggestions that have claimed that basal eutherian relationships have been conclusively settled.     

Mammalian evolution and biomedicine: new views from phylogeny

Recent progress resolving the phylogenetic relationships of the major lineages of mammals has had a broad impact in evolutionary biology, comparative genomics and the biomedical sciences. Novel insights into the timing and historical biogeography of early mammalian diversification have resulted from a new molecular tree for placental mammals coupled with dating approaches that relax the assumption of the molecular clock. We highlight the numerous applications to come from a well-resolved phylogeny and genomic prospecting in multiple lineages of mammals, from identifying regulatory elements in mammalian genomes to assessing the functional consequences of mutations in human disease loci and those driving adaptive evolution.     

Phylogenomic analysis resolves the interordinal relationships and rapid diversification of the laurasiatherian mammals

Although great progress has been made in resolving the relationships of placental mammals, the position of several clades in Laurasiatheria remain controversial. In this study, we performed a phylogenetic analysis of 97 orthologs (46,152 bp) for 15 taxa, representing all laurasiatherian orders. Additionally, phylogenetic trees of laurasiatherian mammals with draft genome sequences were reconstructed based on 1608 exons (2,175,102 bp). Our reconstructions resolve the interordinal relationships within Laurasiatheria and corroborate the clades Scrotifera, Fereuungulata, and Cetartiodactyla. Furthermore, we tested alternative topologies within Laurasiatheria, and among alternatives for the phylogenetic position of Perissodactyla, a sister-group relationship with Cetartiodactyla receives the highest support. Thus, Pegasoferae (Perissodactyla + Carnivora + Pholidota + Chiroptera) does not appear to be a natural group. Divergence time estimates from these genes were compared with published estimates for splits within Laurasiatheria. Our estimates were similar to those of several studies and suggest that the divergences among these orders occurred within just a few million years.     

A Mitogenomic Phylogeny of Living Primates

Primates, the mammalian order including our own species, comprise 480 species in 78 genera. Thus, they represent the third largest of the 18 orders of eutherian mammals. Although recent phylogenetic studies on primates are increasingly built on molecular datasets, most of these studies have focused on taxonomic subgroups within the order. Complete mitochondrial (mt) genomes have proven to be extremely useful in deciphering within-order relationships even up to deep nodes. Using 454 sequencing, we sequenced 32 new complete mt genomes adding 20 previously not represented genera to the phylogenetic reconstruction of the primate tree. With 13 new sequences, the number of complete mt genomes within the parvorder Platyrrhini was widely extended, resulting in a largely resolved branching pattern among New World monkey families. We added 10 new Strepsirrhini mt genomes to the 15 previously available ones, thus almost doubling the number of mt genomes within this clade. Our data allow precise date estimates of all nodes and offer new insights into primate evolution. One major result is a relatively young date for the most recent common ancestor of all living primates which was estimated to 66-69 million years ago, suggesting that the divergence of extant primates started close to the K/T-boundary. Although some relationships remain unclear, the large number of mt genomes used allowed us to reconstruct a robust primate phylogeny which is largely in agreement with previous publications. Finally, we show that mt genomes are a useful tool for resolving primate phylogenetic relationships on various taxonomic levels.     

Molecules consolidate the placental mammal tree

Deciphering relationships among the orders of placental mammals remains an important problem in evolutionary biology and has implications for understanding patterns of morphological character evolution, reconstructing the ancestral placental genome, and evaluating the role of plate tectonics and dispersal in the biogeographic history of this group. Until recently, both molecular and morphological studies provided only a limited and questionable resolution of placental relationships. Studies based on larger and more diverse molecular datasets, and using an array of methodological approaches, are now converging on a stable tree topology with four major groups of placental mammals. The emerging tree has revealed numerous instances of convergent evolution and suggests a role for plate tectonics in the early evolutionary history of placental mammals. The reconstruction of mammalian phylogeny illustrates both the pitfalls and the powers of molecular systematics.     

A molecular perspective on mammalian evolution from the gene encoding interphotoreceptor retinoid binding protein, with convincing evidence for bat monophyly.

The evolutionary relationships of the various orders of placental mammals remain an issue of uncertainty and controversy. Molecular studies of mammalian phylogeny at the DNA level that include more than just a few orders are still relatively meager. Here we report results on mammalian phylogeny deduced from the coding sequence of the single-copy nuclear gene for the interphotoreceptor retinoid binding protein (IRBP). Analysis of 13 species representing eight eutherian orders and one marsupial yielded results that falsify the hypothesis that megachiropteran bats are "flying primates," only convergently resembling microchiropteran bats. Instead, in agreement with more traditional views, as well as those from other recent molecular studies, the results strongly support a monophyletic Chiroptera (micro- and megabats grouped together). The IRBP results also offer some rare molecular support for the Glires concept, in which rodents and lagomorphs form a superordinal grouping. Also in congruence with other recent molecular evidence, IRBP sequences do not support the view of a superorder Archonta that includes Chiroptera along with Dermoptera (flying lemur), Scandentia (tree shrew), and Primates. IRBP was not however, without its shortcomings as a molecular phylogenetic system: high levels of homoplasy, evident in the marsupial outgroup, did not allow us to properly root the tree, and several of the higher level eutherian clades were only weakly supported (e.g., a Carnivora/Chiroptera clade and an Artiodactyla/Carnivora/Chiroptera clade). We suggest that these shortcomings may be diminished as the phylogenetic density of the data set is increased.     

黑素皮质激素受体1（MC1R）基因系统发育树与犬的毛色

犬的驯养迄今约有1万多年,由于不同环境和不同目的人工选择形成了犬品种间或品种内极丰富的毛色多样性,经证实,这些犬的很多毛色类型与MC1R相关 ,MC1R在一些物种中有同源基因 本文阐述了犬MC1R多态性研究进展,并选择其它9个有代表性的哺乳动物物种与犬MC1R同源基因进行了比较,以此建立系统发育树。结果显示,10个物种的MC1R基因的分子进化关系与物种的经典分类学地位基本相符。      

Tracking Marsupial Evolution Using Archaic Genomic Retroposon Insertions

The Australasian and South American marsupial mammals, such as kangaroos and opossums, are the closest living relatives to placental mammals, having shared a common ancestor around 130 million years ago. The evolutionary relationships among the seven marsupial orders have, however, so far eluded resolution. In particular, the relationships between the four Australasian and three South American marsupial orders have been intensively debated since the South American order Microbiotheria was taxonomically moved into the group Australidelphia. Australidelphia is significantly supported by both molecular and morphological data and comprises the four Australasian marsupial orders and the South American order Microbiotheria, indicating a complex, ancient, biogeographic history of marsupials. However, the exact phylogenetic position of Microbiotheria within Australidelphia has yet to be resolved using either sequence or morphological data analysis. Here, we provide evidence from newly established and virtually homoplasy-free retroposon insertion markers for the basal relationships among marsupial orders. Fifty-three phylogenetically informative markers were retrieved after in silico and experimental screening of ∼217,000 retroposon-containing loci from opossum and kangaroo. The four Australasian orders share a single origin with Microbiotheria as their closest sister group, supporting a clear divergence between South American and Australasian marsupials. In addition, the new data place the South American opossums (Didelphimorphia) as the first branch of the marsupial tree. The exhaustive computational and experimental evidence provides important insight into the evolution of retroposable elements in the marsupial genome. Placing the retroposon insertion pattern in a paleobiogeographic context indicates a single marsupial migration from South America to Australia. The now firmly established phylogeny can be used to determine the direction of genomic changes and morphological transitions within marsupials.     

Recapitulating the evolution of Afrotheria: 57 genes and rare genomic changes (RGCs) consolidate their history

The decipherment of higher level relationships among the orders of Afrotheria – an extraordinary assumption in mammalian evolution – constitutes one of the major disputes in the evolutionary history of mammals. Recent comprehensive studies of various genomic data, including mitochondrial and nuclear DNA sequences, chromosomal syntenic associations and retroposon insertions support strongly the monophyly of Afrotheria. However, the relationships within Afrotheria have remained ambiguous and there is a necessity for a more sophisticated analysis (i.e. combination of gene phylogeny and Rare Genomic Changes (RGCs)), which could aid in the comprehension of the evolutionary history of this old group of mammals. The present study investigated the phylogenetic relationships within Afrotheria by analysing a data set of coding and non-coding sequences (～32 000 bp) comprising 57 orthologous genes and 31 RGCs, such as chromosomal associations and retroposon insertions, and re-evaluated a molecular timescale for afrotherian mammals using a Bayesian relaxed clock approach. The interordinal afrotherians phylogeny presented here contributed to the elucidation of the evolutionary history of this ancient clade of mammals, which is one of the most unorthodox proposals in mammalian biology. This is critical not only for understanding how Afrotheria evolved in Africa, but also to comprehend the early biogeographical history of placental mammals.     

The chromosomes of afrotheria and their bearing on Mammalian genome evolution

Afrotheria is the clade of placental mammals that, together with Xenarthra, Euarchontoglires and Laurasiatheria, represents 1 of the 4 main recognized supraordinal eutherian clades. It reunites 6 orders of African origin: Proboscidea, Sirenia, Hyracoidea, Macroscelidea, Afrosoricida and Tubulidentata. The apparently unlikely relationship among such disparate morphological taxa and their possible basal position at the base of the eutherian phylogenetic tree led to a great deal of attention and research on the group. The use of biomolecular data was pivotal in Afrotheria studies, as they were the basis for the recognition of this clade. Although morphological evidence is still scarce, a plethora of molecular data firmly attests to the phylogenetic relationship among these mammals of African origin. Modern cytogenetic techniques also gave a significant contribution to the study of Afrotheria, revealing chromosome signatures for the group as a whole, as well as for some of its internal relationships. The associations of human chromosomes HSA1/19 and 5/21 were found to be chromosome signatures for the group and provided further support for Afrotheria. Additional chromosome synapomorphies were also identified linking elephants and manatees in Tethytheria (the associations HSA2/3, 3/13, 8/22, 18/19 and the lack of HSA4/8) and elephant shrews with the aardvark (HSA2/8, 3/20 and 10/17). Herein, we review the current knowledge on Afrotheria chromosomes and genome evolution. The already available data on the group suggests that further work on this apparently bizarre assemblage of mammals will provide important data to a better understanding on mammalian genome evolution.     

Evolutionary history of mammalian sucking lice (Phthiraptera: Anoplura)

Background  

Sucking lice (Phthiraptera: Anoplura) are obligate, permanent ectoparasites of eutherian mammals, parasitizing members of 12 of the 29 recognized mammalian orders and approximately 20% of all mammalian species. These host specific, blood-sucking insects are morphologically adapted for life on mammals: they are wingless, dorso-ventrally flattened, possess tibio-tarsal claws for clinging to host hair, and have piercing mouthparts for feeding. Although there are more than 540 described species of Anoplura and despite the potential economical and medical implications of sucking louse infestations, this study represents the first attempt to examine higher-level anopluran relationships using molecular data. In this study, we use molecular data to reconstruct the evolutionary history of 65 sucking louse taxa with phylogenetic analyses and compare the results to findings based on morphological data. We also estimate divergence times among anopluran taxa and compare our results to host (mammal) relationships.     

哺乳动物抗凝血酶基因的分子特征、微共线性与适应性进化

抗凝血酶(AT)是哺乳动物体内重要的天然抗凝血因子之一,它隶属于丝氨酸蛋白酶抑制物家族,主要参与并调节复杂的血凝过程。基于比较基因组学手段,共挖掘出17个哺乳动物抗凝血酶基因(AT),并剖析了它们的基因结构、微共线性、保守基序、功能结构域、以及系统进化关系。基因结构与微共线分析表明,哺乳动物AT基因具有5-12个外显子,大多数是7个外显子;不同物种AT基因所处区段之间具有较好的共线性。哺乳动物AT蛋白特征分析显示,SERPIN功能结构域与保守基序1、2、3、4、5、8和9存在相互重叠的部分。AT基因进化树揭示基因进化和通常认为的物种进化几乎一致。同时,利用PAML中Codeml的位点特异模型在AT基因中发掘了1个正选择位点328D。     

Resolution of the laurasiatherian phylogeny: evidence from genomic data

Despite great progress over the past decade, some portions of the mammalian tree of life remain unresolved. In particular, relationships among the different orders included within the supraordinal group Laurasiatheria have been proven difficult to determine, and have received poor support in the vast majority of phylogenomic studies of mammalian systematics. We estimated interordinal relationships within Laurasiatheria using sequence data from 3733 protein-coding genes. Our study included data from from 11 placental mammals, corresponding to five of the six orders of Laurasiatheria, plus five outgroup species. Ingroup and outgroup species were chosen to maximize the number single-copy ortholog genes for which sequence data was available for all species in our study. Phylogenetic analyses of the concatenated dataset using maximum likelihood and Bayesian methods resulted on an identical and well supported topology in all alignment strategies compared. Our analyses provide high support for the sister relationship between Chiroptera and Cetartiodactyla and also provide support for placing Perissodactyla as sister to Carnivora. We obtained maximal estimates of bootstrap support (100%) and posterior probability (1.00) for all nodes within Laurasiatheria. Our study provides a further demonstration of the utility of very large and conserved genomic dataset to clarify our understanding of the evolutionary relationships among mammals.     

Evolutionary relationships of class II major-histocompatibility-complex genes in mammals

The major histocompatibility complex (MHC) class II molecule consists of noncovalently associated alpha and beta chains. In mammals studied so far, the class II MHC can be divided into a number of regions, each containing one or more alpha-chain genes (A genes) and beta-chain genes (B genes), and it has been known for some time that orthologous relationships exist between genes in corresponding regions from different mammalian species. A phylogenetic analysis of DNA sequences of class II A and B genes confirmed these relationships; but no such orthologous relationship was observed between the B genes of mammals and those of birds. Thus, the class II regions have diverged since the separation of birds and mammals (approximately 300 Mya) but before the radiation of the placental mammalian orders (60-80 Mya). Comparison of the phylogenetic trees for A and B genes revealed an unexpected characteristic of DP-region genes: DPB genes are most closely related to DQB genes, whereas DPA chain genes are most closely related to DRA-chain genes. Thus, the DP region seems to have originated through a recombinational event which brought together a DQB gene and a DRA gene (perhaps approximately 120 Mya). The 5' untranslated region of all class II genes includes sequences which are believed to be important in regulating class II gene expression but which are not conserved in known pseudogenes. These sequences are conserved to an extraordinary degree in the human DQB1 gene and its mouse homologue A beta 1, suggesting that regulation of expression of this locus may play a key role in expression of the entire class II MHC.     

Molecules remodel the mammalian tree

DNA sequences provide a direct record of the genealogy of extant species. This tremendous reservoir of phylogenetic information is only beginning to be exploited. If progress in molecular phylogeny is being made, it should be most conspicuous amongst mammals, as their evolution is probably the best-studied. Indeed, surprising changes have recently been proposed for the tree of mammalian orders. These range from grouping whales with hippos, to placing African golden moles closer to elephants than to their fellow insectivores.     

Origins and divergence times of mammalian class II MHC gene clusters

The class I and II major histocompatibility complex (MHC) genes are apparently subject to evolution by a birth-and-death process. The rate of gene turnover is much slower in the latter genes than in the former. In placental mammals, the class II region can be subdivided into different orthologous subregions or gene clusters (DR, DQ, DO, and DN), but the origins and evolutionary relationships of these gene clusters are not well established. Here we report the results of our study of the times of origin and evolutionary relationships of these gene clusters in mammals. Our analysis suggests that both class II alpha-chain and beta-chain gene clusters are shared by placental mammals and marsupials, but the gene clusters from nonmammalian species are paralogous to mammalian gene clusters. We estimated the times of divergence between gene clusters in placental mammals using the linearized tree and distance regression methods. Our results indicate that most gene clusters originated 170-200 million years (MY) ago, but that DO beta-chain genes diverged from the other beta-chain gene clusters approximately 210-260 MY ago. The phylogenetic trees for the alpha- and beta-chain genes were not congruent, suggesting that the evolutionary history of the class II gene clusters is more complex than previously thought.     

Abundant variations of <Emphasis Type="Italic">MC4R</Emphasis> gene revealed by Phylogenies of Yak (<Emphasis Type="Italic">Bos grunniens</Emphasis>) and other mammals

MC4R gene was proved to play important roles in body weight regulation in many mammals and exhibit higher homology among different species. The mutations MC4R significantly correlated to the restricted feeding weight, fat deposition and energy balance. In this work, ORF sequences of MC4R gene of Bos grunniens were cloned and phylogenetic relationships of yak and other mammals were analyzed on the basis of MC4R genes. Totally 290 variable sites were examined in 25 sequences from 22 different mammals, and 23 haplotypes were defined with a haplotype diversity of 0.9900. All the sequences were clustered into phylogenetic clades representing different orders or families. The individuals of Bos grunniens, Bos taurus and Ovis aries which belonged to the family of Bovidae were more divergent from the other orders or families and bovid animals may have branched out from the phylogenetic tree earlier than other mammals analyzed during 450 million years of vertebrate evolution. Amino acid sequences inferred from MC4R genes exhibited 54 variable sites, while high conservation of MC4R was observed within the same order or family. We concluded that coding region of MC4R gene displayed abundant variations among different mammal phylogenetic clades, whereas, the conservation of MC4R within order or family could be explained that MC4R gene may have been subjected to substantial constraints or strong purifying selection during several million years of mammal evolution.     

Novel mammalian herpesviruses and lineages within the Gammaherpesvirinae: cospeciation and interspecies transfer

Novel members of the subfamily Gammaherpesvirinae, hosted by eight mammalian species from six orders (Primates, Artiodactyla, Perissodactyla, Carnivora, Scandentia, and Eulipotyphla), were discovered using PCR with pan-herpesvirus DNA polymerase (DPOL) gene primers and genus-specific glycoprotein B (gB) gene primers. The gB and DPOL sequences of each virus species were connected by long-distance PCR, and contiguous sequences of approximately 3.4 kbp were compiled. Six additional gammaherpesviruses from four mammalian host orders (Artiodactyla, Perissodactyla, Primates, and Proboscidea), for which only short DPOL sequences were known, were analyzed in the same manner. Together with available corresponding sequences for 31 other gammaherpesviruses, alignments of encoded amino acid sequences were made and used for phylogenetic analyses by maximum-likelihood and Bayesian Monte Carlo Markov chain methods to derive a tree which contained two major loci of unresolved branching details. The tree was rooted by parallel analyses that included alpha- and betaherpesvirus sequences. This gammaherpesvirus tree contains 11 major lineages and presents the widest view to date of phylogenetic relationships in any subfamily of the Herpesviridae, as well as the most complex in the number of deep lineages. The tree's branching pattern can be interpreted only in part in terms of the cospeciation of virus and host lineages, and a substantial incidence of the interspecies transfer of viruses must also be invoked.     

Molecular Phylogeny and Evolution of the Neurotrophins from Monotremes and Marsupials

We have investigated the phylogenetic relationships of monotremes and marsupials using nucleotide sequence data from the neurotrophins; nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3). The study included species representing monotremes, Australasian marsupials and placentals, as well as species representing birds, reptiles, and fish. PCR was used to amplify fragments encoding parts of the neurotrophin genes from echidna, platypus, and eight marsupials from four different orders. Phylogenetic trees were generated using parsimony analysis, and support for the different tree structures was evaluated by bootstrapping. The analysis was performed with NGF, BDNF, or NT-3 sequence data used individually as well as with the three neurotrophins in a combined matrix, thereby simultaneously considering phylogenetic information from three separate genes. The results showed that the monotreme neurotrophin sequences associate to either therian or bird neurotrophin sequences and suggests that the monotremes are not necessarily related closer to therians than to birds. Furthermore, the results confirmed the present classification of four Australasian marsupial orders based on morphological characters, and suggested a phylogenetic relationship where Dasyuromorphia is related closest to Peramelemorphia followed by Notoryctemorphia and Diprotodontia. These studies show that sequence data from neurotrophins are well suited for phylogenetic analysis of mammals and that neurotrophins can resolve basal relationships in the evolutionary tree. Received: 27 January 1997 / Accepted: 20 March 1997