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A "Long Indel" model for evolutionary sequence alignment.

We present a new probabilistic model of sequence evolution, allowing indels of arbitrary length, and give sequence alignment algorithms for our model. Previously implemented evolutionary models have allowed (at most) single-residue indels or have introduced artifacts such as the existence of indivisible "fragments." We compare our algorithm to these previous methods by applying it to the structural homology dataset HOMSTRAD, evaluating the accuracy of (1) alignments and (2) evolutionary time estimates. With our method, it is possible (for the first time) to integrate probabilistic sequence alignment, with reliability indicators and arbitrary gap penalties, in the same framework as phylogenetic reconstruction. Our alignment algorithm requires that we evaluate the likelihood of any specific path of mutation events in a continuous-time Markov model, with the event times integrated out. To this effect, we introduce a "trajectory likelihood" algorithm (Appendix A). We anticipate that this algorithm will be useful in more general contexts, such as Markov Chain Monte Carlo simulations.

Algorithms↗

The low evolutionary rate of human T-cell lymphotropic virus type-1 confirmed by analysis of vertical transmission chains.

The evolutionary rate of the human T-cell lymphotropic virus type-1 (HTLV-1) is considered to be very low, in strong contrast to the related human retrovirus HIV. However, current estimates of the HTLV-1 rate rely on the anthropological calibration of phylogenies using assumed dates of human migration events. To obtain an independent rate estimate, we analyzed two variable regions of the HTLV-1 genome (LTR and env) from eight infected families. Remarkable genetic stability was observed, as only two mutations in LTR (756 bp) and three mutations in env (522 bp) occurred within the 16 vertical transmission chains, including one ambiguous position in each region. The evolutionary rate in HTLV-1 was then calculated using a maximum-likelihood approach that used the highest and lowest possible times of HTLV-1 shared ancestry, given the known transmission histories. The rates for the LTR and env regions were 9.58 x 10(-8)-1.25 x 10(-5) and 7.84 x 10(-7) -2.33 x 10(-5)nucleotide substitutions per site per year, respectively. A more precise estimate was obtained for the combined LTR-env data set, which was 7.06 x 10(-7)-1.38 x 10(-5)substitutions per site per year. We also note an interesting correlation between the occurrence of mutations in HTLV-1 and the age of the individual infected.

Adolescent↗

Evolutionary process of amino acid biosynthesis in Corynebacterium at the whole genome level.

Corynebacterium glutamicum, which is the closest relative of Corynebacterium efficiens, is widely used for the large scale production of many kinds of amino acids, particularly glutamic acid and lysine, by fermentation. Corynebacterium diphtheriae, which is well known as a human pathogen, is also closely related to these two species of Corynebacteria, but it lacks such productivity of amino acids. It is an important and interesting question to ask how those closely related bacterial species have undergone such significant functional differentiation in amino acid biosynthesis. The main purpose of the present study is to clarify the evolutionary process of functional differentiation among the three species of Corynebacteria by conducting a comparative analysis of genome sequences. When Mycobacterium and Streptomyces were used as out groups, our comparative study suggested that the common ancestor of Corynebacteria already possessed almost all of the gene sets necessary for amino acid production. However, C. diphtheriae was found to have lost the genes responsible for amino acid production. Moreover, we found that the common ancestor of C. efficiens and C. glutamicum have acquired some of genes responsible for amino acid production by horizontal gene transfer. Thus, we conclude that the evolutionary events of gene loss and horizontal gene transfer must have been responsible for functional differentiation in amino acid biosynthesis of the three species of Corynebacteria.

Amino Acids↗

Microsatellite variation and evolutionary history of PCDHX/Y gene pair within the Xq21.3/Yp11.2 hominid-specific homology block.

To better understand the evolutionary dynamics of repetitive sequences in human sex chromosomes, we have analyzed seven new X/Y homologous microsatellites located within PCDHX/Y, one of the two recently described gene pairs in the Xq21.3/Yp11.2 hominid-specific homology block, in samples from Portugal and Mozambique. Sharp differences were observed on X/Y allele distributions, concerning both the presence of private alleles and a different modal repeat length for X-linked and Y-linked markers, and this difference was statistically significant. Higher diversity was found in X-linked microsatellites than in their Y chromosome counterparts; when comparing populations, Mozambicans showed more allele diversity for the X chromosome, but the contrary was true for the Y chromosome microsatellites. Evolutionary patterns, relying on intragenic PCDHX/Y SNPs, also revealed distinct scenarios for X and Y chromosomes. Greater microsatellite diversity was displayed by African X chromosomes within the most common haplotypes shared by both populations, whereas higher microsatellite diversity was found in Portugal for the ancestral Y chromosome haplotype. The most frequent PCDHY haplotype in Portuguese was the derived one, and it was not found in Mozambicans. TMRCA estimated by the rho parameter resulted in 13,700 years (7,500-20,000 years), which is consistent with a recent, post-Out-of-Africa origin for this haplotype. In conclusion, the newly described microsatellite loci generally displayed greater X-linked to Y-linked diversity and this pattern was also detected with slower evolving markers, with a remarkable differentiation between populations observed for Y chromosome haplotypes and, thus, greater divergence among Y chromosomes in human populations.

Africa↗

The evolutionary repertoires of the eukaryotic-type ABC transporters in terms of the phylogeny of ATP-binding domains in eukaryotes and prokaryotes.

ABC (ATP-binding cassette) transporters play an important role in the communication of various substrates across cell membranes. They are ubiquitous in prokaryotes and eukaryotes, and eukaryotic types (EK-types) are distinguished from prokaryotic types (PK-types) in terms of their genes and domain organizations. The EK-types and PK-types mainly consist of exporters and importers, respectively. Prokaryotes have both the EK-types and the PK-types. The EK-types in prokaryotes are usually called "bacterial multidrug ABC transporters," but they are not well characterized in comparison with the multidrug ABC transporters in eukaryotes. Thus, an exhaustive search of the EK-types among diverse organisms and detailed sequence classification and analysis would elucidate the evolutionary history of EK-types. It would also help shed some light on the fundamental repertoires of the wide variety of substrates through which multidrug ABC transporters in eukaryotes communicate. In this work, we have identified the EK-type ABC transporters in 126 prokaryotes using the profiles of the ATP-binding domain (NBD) of the EK-type ABC transporters from 12 eukaryotes. As a result, 11 clusters were identified from 1,046 EK-types ABC transporters. In particular, two large novel clusters emerged, corresponding to the bacterial multidrug ABC transporters related to the ABCB and ABCC families in eukaryotes, respectively. In the genomic context, most of these genes are located alone or adjacent to genes from the same clusters. Additionally, to detect functional divergences in the NBDs, the Kullback-Leibler divergence was measured among these bacterial multidrug transporters. As a result, several putative functional regions were identified, some corresponding to the predicted secondary structures. We also analyzed a phylogeny of the EK-type ABC transporters in both prokaryotes and eukaryotes, which revealed that the EK-type ABC transporters in prokaryotes have certain repertoires corresponding to the conventional ABC protein groups in eukaryotes. On the basis of these findings, we propose an updated evolutionary hypothesis in which the EK-type ABC transporters in both eukaryotes and prokaryotes consisted of several kinds of ABC transporters in putative ancestor cells before the divergence of eukaryotic and prokaryotic cells.

ATP-Binding Cassette Transporters↗

Evolutionary history of chromosome 20.

The evolutionary history of human chromosome 20 in primates was investigated using a panel of human BAC/PAC probes spaced along the chromosome. Oligonucleotide primers derived from the sequence of each human clone were used to screen horse, cat, pig, and black lemur BAC libraries to assemble, for each species, a panel of probes mapping to chromosomal loci orthologous to the loci encompassed by the human BACs. This approach facilitated marker-order comparison aimed at defining marker arrangement in primate ancestor. To this goal, we also took advantage of the mouse and rat draft sequences. The almost perfect colinearity of chromosome 20 sequence in humans and mouse could be interpreted as evidence that their form was ancestral to primates. Contrary to this view, we found that horse, macaque, and two New World monkeys share the same marker-order arrangement from which the human and mouse forms can be derived, assuming similar but distinct inversions that fully account for the small difference in marker arrangement between humans and mouse. The evolutionary history of this chromosome unveiled also two centromere repositioning events in New World monkey species.

Animals↗

Statistical and molecular analyses of evolutionary significance of red-green color vision and color blindness in vertebrates.

Red-green color vision is strongly suspected to enhance the survival of its possessors. Despite being red-green color blind, however, many species have successfully competed in nature, which brings into question the evolutionary advantage of achieving red-green color vision. Here, we propose a new method of identifying positive selection at individual amino acid sites with the premise that if positive Darwinian selection has driven the evolution of the protein under consideration, then it should be found mostly at the branches in the phylogenetic tree where its function had changed. The statistical and molecular methods have been applied to 29 visual pigments with the wavelengths of maximal absorption at approximately 510-540 nm (green- or middle wavelength-sensitive [MWS] pigments) and at approximately 560 nm (red- or long wavelength-sensitive [LWS] pigments), which are sampled from a diverse range of vertebrate species. The results show that the MWS pigments are positively selected through amino acid replacements S180A, Y277F, and T285A and that the LWS pigments have been subjected to strong evolutionary conservation. The fact that these positively selected M/LWS pigments are found not only in animals with red-green color vision but also in those with red-green color blindness strongly suggests that both red-green color vision and color blindness have undergone adaptive evolution independently in different species.

Animals↗

Evolutionary change of the numbers of homeobox genes in bilateral animals.

It has been known that the conservation or diversity of homeobox genes is responsible for the similarity and variability of some of the morphological or physiological characters among different organisms. To gain some insights into the evolutionary pattern of homeobox genes in bilateral animals, we studied the change of the numbers of these genes during the evolution of bilateral animals. We analyzed 2,031 homeodomain sequences compiled from 11 species of bilateral animals ranging from Caenorhabditis elegans to humans. Our phylogenetic analysis using a modified reconciled-tree method suggested that there were at least about 88 homeobox genes in the common ancestor of bilateral animals. About 50-60 genes of them have left at least one descendant gene in each of the 11 species studied, suggesting that about 30-40 genes were lost in a lineage-specific manner. Although similar numbers of ancestral genes have survived in each species, vertebrate lineages gained many more genes by duplication than invertebrate lineages, resulting in more than 200 homeobox genes in vertebrates and about 100 in invertebrates. After these gene duplications, a substantial number of old duplicate genes have also been lost in each lineage. Because many old duplicate genes were lost, it is likely that lost genes had already been differentiated from other groups of genes at the time of gene loss. We conclude that both gain and loss of homeobox genes were important for the evolutionary change of phenotypic characters in bilateral animals.

Algorithms↗

The "inverse relationship between evolutionary rate and age of mammalian genes" is an artifact of increased genetic distance with rate of evolution and time of divergence.

It has recently been claimed that older genes tend to evolve more slowly than newer ones (Alba and Castresana 2005). By simulation of genes of equal age, we show that the inverse correlation between age and rate is an artifact caused by our inability to detect homology when evolutionary distances are large. Since evolutionary distance increases with time of divergence and rate of evolution, homologs of fast-evolving genes are frequently undetected in distantly related taxa and are, hence, misclassified as "new." This misclassification causes the mean genetic distance of 'new' genes to be overestimated and the mean genetic distance of "old" genes to be underestimated.

Animals↗

Application of phylogenetic networks in evolutionary studies.

The evolutionary history of a set of taxa is usually represented by a phylogenetic tree, and this model has greatly facilitated the discussion and testing of hypotheses. However, it is well known that more complex evolutionary scenarios are poorly described by such models. Further, even when evolution proceeds in a tree-like manner, analysis of the data may not be best served by using methods that enforce a tree structure but rather by a richer visualization of the data to evaluate its properties, at least as an essential first step. Thus, phylogenetic networks should be employed when reticulate events such as hybridization, horizontal gene transfer, recombination, or gene duplication and loss are believed to be involved, and, even in the absence of such events, phylogenetic networks have a useful role to play. This article reviews the terminology used for phylogenetic networks and covers both split networks and reticulate networks, how they are defined, and how they can be interpreted. Additionally, the article outlines the beginnings of a comprehensive statistical framework for applying split network methods. We show how split networks can represent confidence sets of trees and introduce a conservative statistical test for whether the conflicting signal in a network is treelike. Finally, this article describes a new program, SplitsTree4, an interactive and comprehensive tool for inferring different types of phylogenetic networks from sequences, distances, and trees.

Animals↗

On the correlation between composition and site-specific evolutionary rate: implications for phylogenetic inference.

Model-based phylogenetic reconstruction methods traditionally assume homogeneity of nucleotide frequencies among sequence sites and lineages. Yet, heterogeneity in base composition is a characteristic shared by most biological sequences. Compositional variation in time, reflected in the compositional biases among contemporary sequences, has already been extensively studied, and its detrimental effects on phylogenetic estimates are known. However, fewer studies have focused on the effects of spatial compositional heterogeneity within genes. We show here that different sites in an alignment do not always share a unique compositional pattern, and we provide examples where nucleotide frequency trends are correlated with the site-specific rate of evolution in RNA genes. Spatial compositional heterogeneity is shown to affect the estimation of evolutionary parameters. With standard phylogenetic methods, estimates of equilibrium frequencies are found to be biased towards the composition observed at fast-evolving sites. Conversely, the ancestral composition estimates of some time-heterogeneous but spatially homogeneous methods are found to be biased towards frequencies observed at invariant and slow-evolving sites. The latter finding challenges the result of a previous study arguing against a hyperthermophilic last universal ancestor from the low apparent G + C content of its rRNA sequences. We propose a new model to account for compositional variation across sites. A Gaussian process prior is used to allow for a smooth change in composition with evolutionary rate. The model has been implemented in the phylogenetic inference software PHASE, and Bayesian methods can be used to obtain the model parameters. The results suggest that this model can accurately capture the observed trends in present-day RNA sequences.

Evolution, Molecular↗

An evolutionary space-time model with varying among-site dependencies.

It is now widely accepted that sites in a protein do not undergo independent evolutionary processes. The underlying assumption is that proteins are composed of conserved and variable linear domains, and thus rates at neighboring sites are correlated. In this paper, we comprehensively examine the performance of an autocorrelation model of evolutionary rates in protein sequences. We further develop a model in which the level of correlation between rates at adjacent sites is not equal at all sites of the protein. High correlation is expected, for example, in linear functional domains. On the other hand, when we consider nonlinear functional regions (e.g., active sites), low correlation is expected because the interaction between distant sites imposes independence of rates in the linear sequence. Our model is based on a hidden Markov model, which accounts for autocorrelation at certain regions of the protein and rate independence at others. We study the differences between the novel model and models which assume either independence or a fixed level of dependence throughout the protein. Using a diverse set of protein data sets we show that the novel model better fits most data sets. We further analyze the potassium-channel protein family and illustrate the relationship between the dependence of rates at adjacent sites and the tertiary structure of the protein.

Evolution, Molecular↗

Genetic structure and evolutionary history of a diploid hybrid pine Pinus densata inferred from the nucleotide variation at seven gene loci.

Although homoploid hybridization is increasingly recognized as an important phenomenon in plant evolution, its evolutionary genetic mechanisms are poorly documented and understood. Pinus densata, a pine native to the Tibetan Plateau, represents a good example of a homoploid hybrid speciation facilitated by adaptation to extreme environment and ecological isolation from the parents. Its ecologically and reproductively stabilized nature offers excellent opportunity for studying genetic processes associated with hybrid speciation. In this study, we investigated the levels and patterns of nucleotide variation in P. densata and its putative parents. Haplotype composition, gene genealogies, and the levels and patterns of nucleotide variation gave further support to the hybrid nature of P. densata. Allelic history, as revealed by our data, suggests the ancient nature of the hybrid preceding elevation of the Tibetan Plateau. We detected more deviations from neutrality in P. densata than in the parental species. Thus, at least some of the evolutionary forces that have shaped the genetic variation in P. densata are likely to be different from those acting upon parental species. We speculate that when populations of P. densata invaded new territories, they had elevated rates of response to selection in order to develop traits that help them to survive and adapt in the new environments.

Diploidy↗

The evolutionary origin of Xanthomonadales genomes and the nature of the horizontal gene transfer process.

Determining the influence of horizontal gene transfer (HGT) on phylogenomic analyses and the retrieval of a tree of life is relevant for our understanding of microbial genome evolution. It is particularly difficult to differentiate between phylogenetic incongruence due to noise and that resulting from HGT. We have performed a large-scale, detailed evolutionary analysis of the different phylogenetic signals present in the genomes of Xanthomonadales, a group of Proteobacteria. We show that the presence of phylogenetic noise is not an obstacle to infer past and present HGTs during their evolution. The scenario derived from this analysis and other recently published reports reflect the confounding effects on bacterial phylogenomics of past and present HGT. Although transfers between closely related species are difficult to detect in genome-scale phylogenetic analyses, past transfers to the ancestor of extant groups appear as conflicting signals that occasionally might make impossible to determine the evolutionary origin of the whole genome.

Cluster Analysis↗

Genome sequence comparison reveals independent inactivation of the caspase-15 gene in different evolutionary lineages of mammals.

We have recently demonstrated that placental mammalian species such as pig and dog express a novel proapoptotic protease, caspase-15, whereas mouse and humans lack this enzyme. Here we investigated the evolutionary fate of the caspase-15 gene in different mammalian lineages by analyzing whole-genome shotgun sequences of 30 mammalian species for the presence of caspase-15 orthologs. Caspase-15 gene sequences were found in representatives of all major mammalian clades except for the superorders Afrotheria (tenrec, rock hyrax, and elephant) and Euarchontoglires (rodents, rabbit, tree shrew, and primates), which either lacked any caspase-15-like sequences or contained mutated remnants of the caspase-15 gene. Polymerase chain reaction screenings confirmed the results of the database searches and showed that the caspase-15 gene is expressed not only in various placental mammals but also in the marsupial, Monodelphis domestica. The observed species distribution implies that caspase-15 has originated in an early ancestor of modern mammals and has been conserved, over more than 180 Myr, in marsupials and many placental mammals, whereas it was independently lost in 2 phylogenetically distant clades of placental mammals, that is, Afrotheria and Euarchontoglires. Our data suggest that the inactivation of the caspase-15 gene was not counteracted by, and may even have been driven by, evolutionary constraints in these clades, and therefore, caution against the uncritical use of gene absence for the inference of phylogenetic relationships.

Amino Acid Sequence↗

Avian influenza virus exhibits rapid evolutionary dynamics.

Influenza A viruses from wild aquatic birds, their natural reservoir species, are thought to have reached a form of stasis, characterized by low rates of evolutionary change. We tested this hypothesis by estimating rates of nucleotide substitution in a diverse array of avian influenza viruses (AIV) and allowing for rate variation among lineages. The rates observed were extremely high, at >10(-3) substitutions per site, per year, with little difference among wild and domestic host species or viral subtypes and were similar to those seen in mammalian influenza A viruses. Influenza A virus therefore exhibits rapid evolutionary dynamics across its host range, consistent with a high background mutation rate and rapid replication. Using the same approach, we also estimated that the common ancestors of the hemagglutinin and neuraminidase sequences of AIV arose within the last 3,000 years, with most intrasubtype diversity emerging within the last 100 years and suggestive of a continual selective turnover.

Animals↗

On the evolutionary descent of organisms and organelles: a global phylogeny based on a highly conserved structural core in small subunit ribosomal RNA.

To probe the earliest evolutionary events attending the origin of the five known genome types (archaebacterial, eubacterial, nuclear, mitochondrial and plastid), we have analyzed sequences corresponding to a ubiquitous, highly conserved core of secondary structure in small subunit rRNA. Our results support (i) the existence of three primary lineages (archaebacterial, eubacterial, and nuclear), (ii) a specific eubacterial ancestry for plastids and mitochondria (plant, animal, fungal), and (iii) an endosymbiotic, evolutionary origin of the two types of organelle from within distinct groups of eubacteria (blue-green algae (cyanobacteria) in the case of plastids, nonphotosynthetic aerobic bacteria in the case of mitochondria). In addition, our analysis suggests (iv) a biphyletic origin of mitochondria, with animal and fungal mitochondria branching together but separately from plant mitochondria, and (v) a monophyletic origin of plastids. The method described here provides a powerful and generally applicable molecular taxonomic approach towards a global phylogeny encompassing all organisms and organelles.

Animals↗

The evolutionary conservation of DNA polymerase alpha.

The evolutionary conservation of DNA polymerase alpha was assessed by immunological and molecular genetic approaches. Four anti-human KB cell DNA polymerase alpha monoclonal antibodies were tested for their ability to recognize a phylogenetically broad array of eukaryotic DNA polymerases. While the single non-neutralizing antibody used in this study recognizes higher mammalian (human, simian, canine, and bovine) polymerases only, three neutralizing antibodies exhibit greater, but variable, extents of cross-reactivity among vertebrate species. The most highly cross-reactive antibody recognizes a unique epitope on a 165-180 kDa catalytic polypeptide in cell lysates from several eukaryotic sources, as distant from man as the amphibians. Genomic Southern hybridization studies with the cDNA of the human DNA polymerase alpha catalytic polypeptide identify the existence of many consensus DNA sequences within the DNA polymerase genes of vertebrate, invertebrate, plant and unicellular organisms. These findings illustrate the differential evolutionary conservation of four unique epitopes on DNA polymerase alpha among vertebrates and the conservation of specific genetic sequences, presumably reflective of critical functional domains, in the DNA polymerase genes from a broad diversity of living forms.

Animals↗