Phylogenetic relations of humans and African apes from DNA sequences in the psi eta-globin region

Sequences from the upstream and downstream flanking DNA regions of the psi eta-globin locus in Pan troglodytes (common chimpanzee), Gorilla gorilla (gorilla), and Pongo pygmaeus (orangutan, the closest living relative to Homo, Pan, and Gorilla) provided further data for evaluating the phylogenetic relations of humans and African apes. These newly sequenced orthologs [an additional 4.9 kilobase pairs (kbp) for each species] were combined with published psi eta-gene sequences and then compared to the same orthologous stretch (a continuous 7.1-kbp region) available for humans. Phylogenetic analysis of these nucleotide sequences by the parsimony method indicated (i) that human and chimpanzee are more closely related to each other than either is to gorilla and (ii) that the slowdown in the rate of sequence evolution evident in higher primates is especially pronounced in humans. These results indicate that features (for example, knuckle-walking) unique to African apes (but not to humans) are primitive and that even local molecular clocks should be applied with caution.     

Sequencing and analysis of Neanderthal genomic DNA

Our knowledge of Neanderthals is based on a limited number of remains and artifacts from which we must make inferences about their biology, behavior, and relationship to ourselves. Here, we describe the characterization of these extinct hominids from a new perspective, based on the development of a Neanderthal metagenomic library and its high-throughput sequencing and analysis. Several lines of evidence indicate that the 65,250 base pairs of hominid sequence so far identified in the library are of Neanderthal origin, the strongest being the ascertainment of sequence identities between Neanderthal and chimpanzee at sites where the human genomic sequence is different. These results enabled us to calculate the human-Neanderthal divergence time based on multiple randomly distributed autosomal loci. Our analyses suggest that on average the Neanderthal genomic sequence we obtained and the reference human genome sequence share a most recent common ancestor approximately 706,000 years ago, and that the human and Neanderthal ancestral populations split approximately 370,000 years ago, before the emergence of anatomically modern humans. Our finding that the Neanderthal and human genomes are at least 99.5% identical led us to develop and successfully implement a targeted method for recovering specific ancient DNA sequences from metagenomic libraries. This initial analysis of the Neanderthal genome advances our understanding of the evolutionary relationship of Homo sapiens and Homo neanderthalensis and signifies the dawn of Neanderthal genomics.     

The primitive wrist of Homo floresiensis and its implications for hominin evolution

Whether the Late Pleistocene hominin fossils from Flores, Indonesia, represent a new species, Homo floresiensis, or pathological modern humans has been debated. Analysis of three wrist bones from the holotype specimen (LB1) shows that it retains wrist morphology that is primitive for the African ape-human clade. In contrast, Neandertals and modern humans share derived wrist morphology that forms during embryogenesis, which diminishes the probability that pathology could result in the normal primitive state. This evidence indicates that LB1 is not a modern human with an undiagnosed pathology or growth defect; rather, it represents a species descended from a hominin ancestor that branched off before the origin of the clade that includes modern humans, Neandertals, and their last common ancestor.     

Accelerated evolution of conserved noncoding sequences in humans

Changes in gene regulation likely influenced the profound phenotypic divergence of humans from other mammals, but the extent of adaptive substitution in human regulatory sequences remains unknown. We identified 992 conserved noncoding sequences (CNSs) with a significant excess of human-specific substitutions. These accelerated elements were disproportionately found near genes involved in neuronal cell adhesion. To assess the uniqueness of human noncoding evolution, we examined CNSs accelerated in chimpanzee and mouse. Although we observed a similar enrichment near neuronal adhesion genes in chimpanzee, the accelerated CNSs themselves exhibited almost no overlap with those in human, suggesting independent evolution toward different neuronal phenotypes in each species. CNSs accelerated in mouse showed no bias toward neuronal cell adhesion. Our results indicate that widespread cis-regulatory changes in human evolution may have contributed to uniquely human features of brain development and function.     

Inferring nonneutral evolution from human-chimp-mouse orthologous gene trios

Even though human and chimpanzee gene sequences are nearly 99% identical, sequence comparisons can nevertheless be highly informative in identifying biologically important changes that have occurred since our ancestral lineages diverged. We analyzed alignments of 7645 chimpanzee gene sequences to their human and mouse orthologs. These three-species sequence alignments allowed us to identify genes undergoing natural selection along the human and chimp lineage by fitting models that include parameters specifying rates of synonymous and nonsynonymous nucleotide substitution. This evolutionary approach revealed an informative set of genes with significantly different patterns of substitution on the human lineage compared with the chimpanzee and mouse lineages. Partitions of genes into inferred biological classes identified accelerated evolution in several functional classes, including olfaction and nuclear transport. In addition to suggesting adaptive physiological differences between chimps and humans, human-accelerated genes are significantly more likely to underlie major known Mendelian disorders.     

Reconstructing the origin of Andaman Islanders

The origin of the Andaman "Negrito" and Nicobar "Mongoloid" populations has been ambiguous. Our analyses of complete mitochondrial DNA sequences from Onges and Great Andaman populations revealed two deeply branching clades that share their most recent common ancestor in founder haplogroup M, with lineages spread among India, Africa, East Asia, New Guinea, and Australia. This distribution suggests that these two clades have likely survived in genetic isolation since the initial settlement of the islands during an out-of-Africa migration by anatomically modern humans. In contrast, Nicobarese sequences illustrate a close genetic relationship with populations from Southeast Asia.     

牦牛线粒体基因组研究进展

系统了解牦牛线粒体基因组(mtDNA)的研究现状,探究其存在的缺陷与不足,为今后更好地开展牦牛基因组学研究提供依据和基础材料。笔者通过查阅近20年有关牦牛mtDNA研究的文献资料,对牦牛mtDNA全序列和部分序列的研究进展进行综述。自20世纪80年代末以来,mtDNA作为一种很好的分子标记已被研究者用于探究牦牛的起源驯化、遗传多样性、迁徙模式、历史发展动态、分类学地位、适应性机理及系统发育关系等问题,并取得了具有结论性的诸多成果。然而,有关牦牛mtDNA全序列基础上的群体基因组学研究、线粒体转录组和蛋白质组学研究、核基因组与线粒体基因组间的互作和调控研究、线粒体基因组与部分性状间的关联分析等内容,还有待继续深入研究。     

A human-specific gene in microglia

Recent studies have shown multiple differences between humans and apes in sialic acid (Sia) biology, including Siglecs (Sia-recognizing-Ig-superfamily lectins). Comparisons with the chimpanzee genome indicate that human SIGLEC11 emerged through human-specific gene conversion by an adjacent pseudogene. Conversion involved 5 cent untranslated sequences and the Sia-recognition domain. This human protein shows reduced binding relative to the ancestral form but recognizes oligosialic acids, which are enriched in the brain. SIGLEC11 is expressed in human but not in chimpanzee brain microglia. Further studies will determine if this event was related to the evolution of Homo.     

Chromosomal speciation and molecular divergence--accelerated evolution in rearranged chromosomes

Humans and their closest evolutionary relatives, the chimpanzees, differ in approximately 1.24% of their genomic DNA sequences. The fraction of these changes accumulated during the speciation processes that have separated the two lineages may be of special relevance in understanding the basis of their differences. We analyzed human and chimpanzee sequence data to search for the patterns of divergence and polymorphism predicted by a theoretical model of speciation. According to the model, positively selected changes should accumulate in chromosomes that present fixed structural differences, such as inversions, between the two species. Protein evolution was more than 2.2 times faster in chromosomes that had undergone structural rearrangements compared with colinear chromosomes. Also, nucleotide variability is slightly lower in rearranged chromosomes. These patterns of divergence and polymorphism may be, at least in part, the molecular footprint of speciation events in the human and chimpanzee lineages.     

Genetic evidence for an East Asian origin of domestic dogs

The origin of the domestic dog from wolves has been established, but the number of founding events, as well as where and when these occurred, is not known. To address these questions, we examined the mitochondrial DNA (mtDNA) sequence variation among 654 domestic dogs representing all major dog populations worldwide. Although our data indicate several maternal origins from wolf, >95% of all sequences belonged to three phylogenetic groups universally represented at similar frequencies, suggesting a common origin from a single gene pool for all dog populations. A larger genetic variation in East Asia than in other regions and the pattern of phylogeographic variation suggest an East Asian origin for the domestic dog, approximately 15,000 years ago.     

Investigation of mitochondrial DNA genetic diversity and phylogeny of goats worldwide

Genetic diversity, population structure, and population expansion of goats worldwide (4 165 individuals from 196 breeds) were analyzed using published mitochondrial DNA (mtDNA) D_loop hypervariable region sequences. Results showed that 2 409 haplotypes and 301 polymorphic sites were present within the 401-bp length D_loop region, the nucleotide diversity (Pi) was 0.03471, and the haplotype diversity (Hd) was 0.9983. Phylogenetic analysis revealed that 98.92% of haplotypes were divided into six obvious clusters, consistent with the classification of the known mitochondrial haplogroups of goats. Haplogroup A accounted for the largest proportion (86%). Interestingly, two unknown divisions (Unknown I and Unknown II) were discovered from goats in Southwest China, suggesting that Southwest China has unique maternal haplogroups. Analysis of molecular variance (AMOVA) and the average number of pairwise differences between populations (PiXY) indicated that geographical variation was small but significant. Neutrality tests (Tajima's D and Fu's F_S tests) and mismatch distribution showed that haplogroups B, C, and G had expansion histories. In addition, the phylogenetic relationship between domestic and wild goats suggested that Capra aegagrus is the most likely wild ancestor and may have participated in the domestication of ancestral populations of A, B, C, and F haplogroups. A meta-analysis on the mtDNA sequences of goats from international databases was conducted to analyze goats’ genetic diversity, population structure, and matrilineal system evolution worldwide. The results may help further understand the domestication history and gene flow of goats worldwide.     

Modern turtle origins: the oldest known cryptodire

The discovery of a turtle in the Early Jurassic(185 million years before present) Kayenta Formation of northeastern Arizona provides significant evidence about the origin of modern turtles. This new taxon possesses many of the primitive features expected in the hypothetical common ancestor of pleurodires and cryptodires, the two groups of modern turtles. It is identified as the oldest known cryptodire because of the presence of a distinctive cryptodiran jaw mechanism consisting of a trochlea over the otic chamber that redirects the line of action of the adductor muscle. Aquatic habits appear to have developed very early in turtle evolution. Kayentachelys extends the known record of cryptodires back at least 45 million years and documents a very early stage in the evolution of modern turtles.     

中国家驴品种遗传多样性及母系起源研究

为了给中国家驴遗传资源的评价、保护和利用提供一些分子生物学基础,本研究通过自行设计引物,采用PCR-SSCP技术对中国家驴线粒体DNA( Mitochondrial DNA,mtDNA)细胞色素b(Cytochrome b,Cytb)基因308bp片段序列的变异进行检测来探讨其遗传多样性和母系起源.发现了3种基因型,结合GenBank已公布的数据进行分析发现在中国家驴品种中共存在15个突变位点,17个单倍型,通过计算各群体的遗传多样性指数发现中国家驴的遗传多样性比较丰富.另外,还通过与两种非洲野驴的Cytb序列进行比对和网络聚类分析方法对所有家驴的样品进行了母系起源的研究,证明家驴起源于非洲的索马里驴和努比亚驴.     

Parallel patterns of evolution in the genomes and transcriptomes of humans and chimpanzees

The determination of the chimpanzee genome sequence provides a means to study both structural and functional aspects of the evolution of the human genome. Here we compare humans and chimpanzees with respect to differences in expression levels and protein-coding sequences for genes active in brain, heart, liver, kidney, and testis. We find that the patterns of differences in gene expression and gene sequences are markedly similar. In particular, there is a gradation of selective constraints among the tissues so that the brain shows the least differences between the species whereas liver shows the most. Furthermore, expression levels as well as amino acid sequences of genes active in more tissues have diverged less between the species than have genes active in fewer tissues. In general, these patterns are consistent with a model of neutral evolution with negative selection. However, for X-chromosomal genes expressed in testis, patterns suggestive of positive selection on sequence changes as well as expression changes are seen. Furthermore, although genes expressed in the brain have changed less than have genes expressed in other tissues, in agreement with previous work we find that genes active in brain have accumulated more changes on the human than on the chimpanzee lineage.     

Genetic and fossil evidence for the origin of modern humans

The origin of living Homo sapiens has once again been the subject of much debate. Genetic data on present human population relationships and data from the Pleistocene fossil hominid record are used to compare two contrasting models for the origin of modern humans. Both genetics and paleontology support a recent African origin for modern humans rather than a long period of multiregional evolution accompanied by gene flow.     

Inserted sequences in bovine satellite DNA's

The nucleotide sequence of the 1413-base-pair repeat unit of bovine 1.711a satellite DNA (density in cesium chloride, 1.711 grams per cubic centimeter) has been determined. The repeat unit contains two segments consisting of variants of a basic 23-base-pair sequence that is closely related to sequences of bovine 1.706 satellite DNA. A third segment of the repeat unit contains an unrelated 611-base-pair sequence that is not internally repetitive. This segment is flanked by inverted repeats of 8 base pairs and, on one side, by a direct repeat of the terminal sequence. A related segment is present in bovine 1.711b satellite DNA and is inserted into sequences derived from the 1.715 satellite. These nucleotide sequences suggest the timing of some of the stages in the evolution of these complex, closely related satellite DNA's and indicate the mechanisms inherent in their divergence from a common ancestor.     

Vertebrate-type intron-rich genes in the marine annelid Platynereis dumerilii

Previous genome comparisons have suggested that one important trend in vertebrate evolution has been a sharp rise in intron abundance. By using genomic data and expressed sequence tags from the marine annelid Platynereis dumerilii, we provide direct evidence that about two-thirds of human introns predate the bilaterian radiation but were lost from insect and nematode genomes to a large extent. A comparison of coding exon sequences confirms the ancestral nature of Platynereis and human genes. Thus, the urbilaterian ancestor had complex, intron-rich genes that have been retained in Platynereis and human.     

Whole-genome shotgun assembly and analysis of the genome of Fugu rubripes

The compact genome of Fugu rubripes has been sequenced to over 95% coverage, and more than 80% of the assembly is in multigene-sized scaffolds. In this 365-megabase vertebrate genome, repetitive DNA accounts for less than one-sixth of the sequence, and gene loci occupy about one-third of the genome. As with the human genome, gene loci are not evenly distributed, but are clustered into sparse and dense regions. Some "giant" genes were observed that had average coding sequence sizes but were spread over genomic lengths significantly larger than those of their human orthologs. Although three-quarters of predicted human proteins have a strong match to Fugu, approximately a quarter of the human proteins had highly diverged from or had no pufferfish homologs, highlighting the extent of protein evolution in the 450 million years since teleosts and mammals diverged. Conserved linkages between Fugu and human genes indicate the preservation of chromosomal segments from the common vertebrate ancestor, but with considerable scrambling of gene order.     

Discovery of a major D-loop replication origin reveals two modes of human mtDNA synthesis

Mammalian mitochondrial DNA (mtDNA) replication has long been considered to occur by asymmetric synthesis of the two strands, starting at the multiple origins of the strand-displacement loop (D-loop). We report the discovery of a major replication origin at position 57 in the D-loop of several human cell lines (HeLa, A549, and 143B.TK-) and immortalized lymphocytes. The nascent chains starting at this origin, in contrast to those initiated at the previously described origins, do not terminate prematurely at the 3' end of the D-loop but proceed well beyond this control point, behaving as "true" replicating strands. This origin is mainly responsible for mtDNA maintenance under steady-state conditions, whereas mtDNA synthesis from the formerly identified D-loop origins may be more important for recovery after mtDNA depletion and for accelerating mtDNA replication in response to physiological demands.     

Paleontology. Shaking the earliest branches of anthropoid primate evolution

Primates living today are believed to share a common ancestor that originated in either Africa or Asia. Fossil examples of such anthropoid ancestors have been found in both continents, so pushing back the origins to a single location has been controversial. In their Perspective, Jaeger and Marivaux discuss results reported in the same issue by Seiffert et al. that may put part of the controversy to rest. Seiffert et al. describe the earliest and most complete African anthropoid fossils from the Fayum desert region of Egypt. Cranial and dental fossils of two different small species were found, and their character, especially the features of the fossil teeth, suggests an ancient evolutionary history in Africa. At the same time, the phylogenetic analysis of Seiffert et al. is consistent with the view that African anthropoids immigrated from Asia at a very early date, probably before the late Paleocene (60 million years ago), possibly followed by later waves of immigration.