Why individual thermo sensation and pain perception varies? Clue of disruptive mutations in TRPVs from 2504 human genome data

Every individual varies in character and so do their sensory functions and perceptions. The molecular mechanism and the molecular candidates involved in these processes are assumed to be similar if not same. So far several molecular factors have been identified which are fairly conserved across the phylogenetic tree and are involved in these complex sensory functions. Among all, members belonging to Transient Receptor Potential (TRP) channels have been widely characterized for their involvement in thermo-sensation. These include TRPV1 to TRPV4 channels which reveal complex thermo-gating behavior in response to changes in temperature. The molecular evolution of these channels is highly correlative with the thermal response of different species. However, recent 2504 human genome data suggest that these thermo-sensitive TRPV channels are highly variable and carry possible deleterious mutations in human population. These unexpected findings may explain the individual differences in terms of complex sensory functions.     

The utility of cranial ontogeny for phylogenetic inference: a case study in crocodylians using geometric morphometrics

The degree to which the ontogeny of organisms could facilitate our understanding of phylogenetic relationships has long been a subject of contention in evolutionary biology. The famed notion that ‘ontogeny recapitulates phylogeny’ has been largely discredited, but there remains an expectation that closely related organisms undergo similar morphological transformations throughout ontogeny. To test this assumption, we used three‐dimensional geometric morphometric methods to characterize the cranial morphology of 10 extant crocodylian species and construct allometric trajectories that model the post‐natal ontogenetic shape changes. Using time‐calibrated molecular and morphological trees, we employed a suite of comparative phylogenetic methods to assess the extent of phylogenetic signal in these trajectories. All analyses largely demonstrated a lack of significant phylogenetic signal, indicating that ontogenetic shape changes contain little phylogenetic information. Notably, some Mantel tests yielded marginally significant results when analysed with the morphological tree, which suggest that the underlying signal in these trajectories is correlated with similarities in the adult cranial morphology. However, despite these instances, all other analyses, including more powerful tests for phylogenetic signal, recovered statistical and visual evidence against the assumption that similarities in ontogenetic shape changes are commensurate with phylogenetic relatedness and thus bring into question the efficacy of using allometric trajectories for phylogenetic inference.     

Rare genomic changes as a tool for phylogenetics

DNA sequence data have offered valuable insights into the relationships between living organisms. However, most phylogenetic analyses of DNA sequences rely primarily on single nucleotide substitutions, which might not be perfect phylogenetic markers. Rare genomic changes (RGCs), such as intron indels, retroposon integrations, signature sequences, mitochondrial and chloroplast gene order changes, gene duplications and genetic code changes, provide a suite of complementary markers with enormous potential for molecular systematics. Recent exploitation of RGCs has already started to yield exciting phylogenetic information.     

Evolutionary change of restriction cleavage sites and phylogenetic inference for man and apes

A mathematical theory for the evolutionary change of restriction endonuclease cleavage sites is developed, and the probabilities of various types of restriction-site changes are evaluated. A computer simulation is also conducted to study properties of the evolutionary change of restriction sites. These studies indicate that parsimony methods of constructing phylogenetic trees often make erroneous inferences about evolutionary changes of restriction sites unless the number of nucleotide substitutions per site is less than 0.01 for all branches of the tree. This introduces a systematic error in estimating the number of mutational changes for each branch and, consequently, in constructing phylogenetic trees. Therefore, parsimony methods should be used only in cases where nucleotide sequences are closely related. Reexamination of Ferris et al.'s data on restriction-site differences of mitochondrial DNAs does not support Templeton's conclusions regarding the phylogenetic tree for man and apes and the molecular clock hypothesis. Templeton's claim that Nei and Li's method of estimating the number of nucleotide substitutions per site is seriously affected by parallel losses and loss-gains of restriction sites is also unsupported.      

Intergenic sequence comparison of Escherichia coli isolates reveals lifestyle adaptations but not host specificity

Establishing the risk of human infection is one of the goals of public health. For bacterial pathogens, the virulence and zoonotic potential can often be related to their host source. Escherichia coli bacteria are common contaminants of water associated with human recreation and consumption, and many strains are pathogenic. In this study, we analyzed three promoter-containing intergenic regions from 284 diverse E. coli isolates in an attempt to identify molecular signatures associated with specific host types. Promoter sequences controlling production of curli fimbriae, flagella, and nutrient import yielded a phylogenetic tree with isolates clustered by established phylogenetic grouping (A, B1, B2, and D) but not by host source. Virulence genes were more prevalent in groups B2 and D isolates and in human isolates. Group B1 isolates, primarily from nonhuman sources, were the most genetically similar, indicating that they lacked molecular adaptations to specific host environments and were likely host generalists. Conversely, B2 isolates, primarily from human sources, displayed greater genetic distances and were more likely to be host adapted. In agreement with these hypotheses, prevalence of σ(S) activity and the rdar morphotype, phenotypes associated with environmental survival, were significantly higher in B1 isolates than in B2 isolates. Based on our findings, we speculate that E. coli host specificity is not defined by genome-wide sequence changes but, rather, by the presence or absence of specific genes and associated promoter elements. Furthermore, the requirements for colonization of the human gastrointestinal tract may lead to E. coli lifestyle changes along with selection for increased virulence.     

Recreating ancestral proteins

Tracing the history of molecular changes using phylogenetic methods can provide powerful insights into how and why molecules work the way they do. It is now possible to recreate inferred ancestral proteins in the laboratory and study the function of these molecules. This provides a unique opportunity to study the paths and the mechanisms of functional change during molecular evolution. What insights have already emerged from such phylogenetic studies of protein evolution and function, what are the impediments to progress and what are the prospects for the future?     

Remarkable consistency of exon-intron structure of hatching enzyme genes and molecular phylogenetic relationships of teleostean fishes

The phylogenetic positions of various fishes in the Teleostei are frequently confused. One such confusion is in the phylogenetic relationships among Salmoniformes, Esociformes, Osmeriformes, Argentiniformes and Alepocephaliformes. While morphology-based phylogenetic studies suggested that all of these belong to Euteleostei, molecule-based phylogenetic analyses indicated that the former four orders belong to the Euteleostei, and the Alepocephaliformes to the Otocephala. In addition, the phylogenetic relationships among the former four orders have not been established: morphological studies have proposed various hypotheses, while molecular analyses have suggested esociforms and salmoniforms to be sister groups at the basal position in euteleosts. In this study, we examined their controversial phylogenetic positions using exon-intron structures of hatching enzyme genes. The gene structures of alepocephaliforms were characteristic to those of lower otocephalans. Those of argentiniforms and osmeriforms were the same as those of higher euteleosts, but different from those of salmoniforms and esociforms. The results suggest that alepocephaliforms are closely related to otocephalans, and salmoniforms form a sister group to esociforms in euteleosts. Therefore, changes in exon-intron structure of hatching enzyme genes correspond well with the molecular phylogenetic relationship estimated from mitochondrial DNA sequences.     

The phylogeny of Xantusiid lizards: The concern for analysis in the search for a best estimate of phylogeny

In the onrush of molecular-based phylogenetic hypotheses, previous morphological-based phylogenies are being ignored, discarded, or even treated with disdain. Coupled with this implicit superiority of molecular data is the sometimes tendency to construct a phylogeny from the molecular data with less than analytical rigor. This paper examines the phylogenetic relationships within the lizard family Xantusiidae employing both molecular and morphological data. The analysis focuses on four analytical points of the molecular data and on the phylogenetics synthesis of the two data sets. We conclude that the phylogeny of xantusiid lizards is not yet a robust hypothesis.     

Evaluation of the internal transcribed spacer 2 (ITS2) as a molecular marker for phylogenetic inference using sequence and secondary structure information in blow flies (Diptera: Calliphoridae)

The internal transcribed spacer 2 (ITS2) is a small non-coding region located inside the nuclear ribosomal DNA cluster. ITS2 sequence variability is thought to be appropriate to differentiate species and for phylogenetic reconstructions analyses, which can be further improved if structural information is considered. We evaluated the potential of ITS2 as a molecular marker for phylogenetic inference in Calliphoridae (Diptera: Brachycera) using a broad range of inference methods and different substitution models, accounting or not for structural information. Sequence analyses revealed a hierarchically organized pattern of sequence variation and a small level of nucleotide substitution saturation. Intragenomic variation due to small sequence repeats was found mainly in the most variable domain (IV), but it has no significant impact on the phylogenetic signal at the species level. Inferred secondary structures revealed that GC pairs are more frequently found flanking bulges and loops regions in more conserved domains, thus ensuring structure stability. In the phylogenetic analyses, the use of substitution models accounting for structural information significantly improves phylogenetic inference in both neighbour-joining and Bayesian analyses, although the former provides limited resolution for dealing with highly divergent sequences. For Bayesian analyses, a significant improvement in likelihood was observed when considering structure information, although with small changes in topology and overall support, probably reflecting better evolutionary rates estimates. Based on these findings, ITS2 is a suitable molecular marker for phylogenetic analyses in Calliphoridae, at both species and generic level.     

Evolutionary anthropology and genes: Investigating the genetics of human evolution from excavated skeletal remains

The development of molecular tools for the extraction, analysis and interpretation of DNA from the remains of ancient organisms (paleogenetics) has revolutionised a range of disciplines as diverse as the fields of human evolution, bioarchaeology, epidemiology, microbiology, taxonomy and population genetics. The paper draws attention to some of the challenges associated with the extraction and interpretation of ancient DNA from archaeological material, and then reviews the influence of paleogenetics on the field of human evolution. It discusses the main contributions of molecular studies to reconstructing the evolutionary and phylogenetic relationships between extinct hominins (human ancestors) and anatomically modern humans. It also explores the evidence for evolutionary changes in the genetic structure of anatomically modern humans in recent millennia. This breadth of research has led to discoveries that would never have been possible using traditional approaches to human evolution.     

Understanding phylogenetic incongruence: lessons from phyllostomid bats

All characters and trait systems in an organism share a common evolutionary history that can be estimated using phylogenetic methods. However, differential rates of change and the evolutionary mechanisms driving those rates result in pervasive phylogenetic conflict. These drivers need to be uncovered because mismatches between evolutionary processes and phylogenetic models can lead to high confidence in incorrect hypotheses. Incongruence between phylogenies derived from morphological versus molecular analyses, and between trees based on different subsets of molecular sequences has become pervasive as datasets have expanded rapidly in both characters and species. For more than a decade, evolutionary relationships among members of the New World bat family Phyllostomidae inferred from morphological and molecular data have been in conflict. Here, we develop and apply methods to minimize systematic biases, uncover the biological mechanisms underlying phylogenetic conflict, and outline data requirements for future phylogenomic and morphological data collection. We introduce new morphological data for phyllostomids and outgroups and expand previous molecular analyses to eliminate methodological sources of phylogenetic conflict such as taxonomic sampling, sparse character sampling, or use of different algorithms to estimate the phylogeny. We also evaluate the impact of biological sources of conflict: saturation in morphological changes and molecular substitutions, and other processes that result in incongruent trees, including convergent morphological and molecular evolution. Methodological sources of incongruence play some role in generating phylogenetic conflict, and are relatively easy to eliminate by matching taxa, collecting more characters, and applying the same algorithms to optimize phylogeny. The evolutionary patterns uncovered are consistent with multiple biological sources of conflict, including saturation in morphological and molecular changes, adaptive morphological convergence among nectar‐feeding lineages, and incongruent gene trees. Applying methods to account for nucleotide sequence saturation reduces, but does not completely eliminate, phylogenetic conflict. We ruled out paralogy, lateral gene transfer, and poor taxon sampling and outgroup choices among the processes leading to incongruent gene trees in phyllostomid bats. Uncovering and countering the possible effects of introgression and lineage sorting of ancestral polymorphism on gene trees will require great leaps in genomic and allelic sequencing in this species‐rich mammalian family. We also found evidence for adaptive molecular evolution leading to convergence in mitochondrial proteins among nectar‐feeding lineages. In conclusion, the biological processes that generate phylogenetic conflict are ubiquitous, and overcoming incongruence requires better models and more data than have been collected even in well‐studied organisms such as phyllostomid bats.     

Empirical support for a stochastic model of evolution

Summary The stochastic model of molecular evolution was used to makea priori predictions for the total number of one-step nucleotide changes required to account for a given number of amino acid substitutions between two homologous proteins. These predictions are now found to be concordant with empirical data summarized by Dayhoff, Eck and Park (1969). Correction factors are derived for adjusting the leg lengths of phylogenetic trees. It is shown that the operations of constructing the phylogenetic tree and applying the correction algorithm are not commutative with respect to obtaining the leg lengths. The effect of this on certain published phylogenies is discussed. It is suggested that, as a first approximation, at any given point in evolutionary time, enthalpic (selective) forces determine the number and position of those codon sites which are free to vary, whereas within these variable sites, entropic (random) processes determine the course of evolution at the molecular level.     

A mixed branch length model of heterotachy improves phylogenetic accuracy

Evolutionary relationships are typically inferred from molecular sequence data using a statistical model of the evolutionary process. When the model accurately reflects the underlying process, probabilistic phylogenetic methods recover the correct relationships with high accuracy. There is ample evidence, however, that models commonly used today do not adequately reflect real-world evolutionary dynamics. Virtually all contemporary models assume that relatively fast-evolving sites are fast across the entire tree, whereas slower sites always evolve at relatively slower rates. Many molecular sequences, however, exhibit site-specific changes in evolutionary rates, called "heterotachy." Here we examine the accuracy of 2 phylogenetic methods for incorporating heterotachy, the mixed branch length model--which incorporates site-specific rate changes by summing likelihoods over multiple sets of branch lengths on the same tree--and the covarion model, which uses a hidden Markov process to allow sites to switch between variable and invariable as they evolve. Under a variety of simple heterogeneous simulation conditions, the mixed model was dramatically more accurate than homotachous models, which were subject to topological biases as well as biases in branch length estimates. When data were simulated with strong versions of the types of heterotachy observed in real molecular sequences, the mixed branch length model was more accurate than homotachous techniques. Analyses of empirical data sets confirmed that the mixed branch length model can improve phylogenetic accuracy under conditions that cause homotachous models to fail. In contrast, the covarion model did not improve phylogenetic accuracy compared with homotachous models and was sometimes substantially less accurate. We conclude that a mixed branch length approach, although not the solution to all phylogenetic errors, is a valuable strategy for improving the accuracy of inferred trees.     

Phylogenetic Framework and Molecular Signatures for the Main Clades of the Phylum Actinobacteria

Summary: The phylum Actinobacteria harbors many important human pathogens and also provides one of the richest sources of natural products, including numerous antibiotics and other compounds of biotechnological interest. Thus, a reliable phylogeny of this large phylum and the means to accurately identify its different constituent groups are of much interest. Detailed phylogenetic and comparative analyses of >150 actinobacterial genomes reported here form the basis for achieving these objectives. In phylogenetic trees based upon 35 conserved proteins, most of the main groups of Actinobacteria as well as a number of their superageneric clades are resolved. We also describe large numbers of molecular markers consisting of conserved signature indels in protein sequences and whole proteins that are specific for either all Actinobacteria or their different clades (viz., orders, families, genera, and subgenera) at various taxonomic levels. These signatures independently support the existence of different phylogenetic clades, and based upon them, it is now possible to delimit the phylum Actinobacteria (excluding Coriobacteriia) and most of its major groups in clear molecular terms. The species distribution patterns of these markers also provide important information regarding the interrelationships among different main orders of Actinobacteria. The identified molecular markers, in addition to enabling the development of a stable and reliable phylogenetic framework for this phylum, also provide novel and powerful means for the identification of different groups of Actinobacteria in diverse environments. Genetic and biochemical studies on these Actinobacteria-specific markers should lead to the discovery of novel biochemical and/or other properties that are unique to different groups of Actinobacteria.     

Cranial shape and correlated characters in crocodilian evolution

Crocodilians show a high degree of cranial variation and convergence throughout their 80 million-year fossil record that complicates their phylogenetic reconstruction. Conflicting phylogenetic results from different data partitions and character homoplasies typify crocodilian phylogeny, and differences between molecular and morphological phylogenetic hypotheses are believed to be associated with the slender-snout skull shape of Gavialis gangeticus and Tomistoma schlegelii. Slender-snout skulls are one of five identified eusuchian cranial ecomorph shape categories (ESCs) thought to reflect functional or ecological specialization. This paper tested the effect of transitions among general, blunt and slender ESCs on cranial character-state distributions in phylogeny using the concentrated changes test. In addition, 'tree-free' character compatibility analysis of character independence was conducted on the morphological character matrix to determine if character correlations are observed independent of specific tree topologies. Results suggest cranial ESCs do affect cranial character-state gains in phylogeny. Concentrated changes identify a broad suite of character-state changes that significantly correlate with transitions to slender, general and blunt ESCs on morphological, molecular and combined-data tree topologies, but numbers of correlated characters for each category differ according to topology. Character compatibility analysis results do not mirror the concentrated changes test results and reflect hierarchically distributed support throughout the data. As cranial ESCs affect character-state transitions, it is possible that nonphylogenetic variables could affect inferences of crocodilian phylogeny by affecting cranial morphology.     

Microsatellite Behavior with Range Constraints: Parameter Estimation and Improved Distances for Use in Phylogenetic Reconstruction

A symmetric stepwise mutation model with reflecting boundaries is employed to evaluate microsatellite evolution under range constraints. Methods of estimating range constraints and mutation rates under the assumptions of the model are developed. Least squares procedures are employed to improve molecular distance estimation for use in phylogenetic reconstruction in the case where range constraints and mutation rates vary across loci. The bias and accuracy of these methods are evaluated using computer simulations, and they are compared to previously existing methods which do not assume range constraints. Range constraints are seen to have a substantial impact on phylogenetic conclusions based on molecular distances, particularly for more divergent taxa. Results indicate that if range constraints are in effect, the methods developed here should be used in both the preliminary planning and final analysis of phylogenetic studies employing microsatellites. It is also seen that in order to make accurate phylogenetic inferences under range constraints, a larger number of loci are required than in their absence.     

Testing for differences in rates-across-sites distributions in phylogenetic subtrees

It has long been recognized that the rates of molecular evolution vary amongst sites in proteins. The usual model for rate heterogeneity assumes independent rate variation according to a rate distribution. In such models the rate at a site, although random, is assumed fixed throughout the evolutionary tree. Recent work by several groups has suggested that rates at sites often vary across subtrees of the larger tree as well as across sites. This phenomenon is not captured by most phylogenetic models but instead is more similar to the covarion model of Fitch and coworkers. In this article we present methods that can be useful in detecting whether different rates occur in two different subtrees of the larger tree and where these differences occur. Parametric bootstrapping and orthogonal regression methodologies are used to test for rate differences and to make statements about the general differences in the rates at sites. Confidence intervals based on the conditional distributions of rates at sites are then used to detect where the rate differences occur. Such methods will be helpful in studying the phylogenetic, structural, and functional bases of changes in evolutionary rates at sites, a phenomenon that has important consequences for deep phylogenetic inference.     

Phylogenetic analysis of the African papionin basicranium using 3‐D geometric morphometrics: The need for improved methods to account for allometric effects

The basicranium has been argued to contain a strong phylogenetic signal in previous analyses of primate cranial morphology. Therefore, further study of basicranial morphology may offer new insights into controversial phylogenetic relationships within primate groups. In this study, I apply 3‐D geometric morphometric techniques in a phylogenetic analysis of the African papionin basicranium. The effects of allometry strongly influence African papionin basicranial morphology and, unless these size effects are controlled or eliminated, phylogenetic analyses suggest traditional phylogenetic groupings of small taxa (mangabeys) and large taxa (geladas, mandrills, drills, and baboons). When the effects of allometry are eliminated by excluding size‐correlated principal components (PCs) or by regression analysis with retention of residuals, phylogenetic analyses of African papionin basicranial morphology are incongruent with recent molecular and morphological studies. By contrast, a cladistic analysis of basicranial characters using the narrow allometric coding method suggests the same phylogenetic relationships as recent molecular and morphological studies. These results suggest that important phylogenetic information is contained within the size‐correlated data, and this information is being discarded during the attempt to eliminate the effects of body size. Future 3‐D morphometric studies of phylogeny should focus on the development of new methodologies to adjust for allometric effects, as current techniques appear to be ill‐equipped to deal with the case of a size‐disparate, lower‐level taxonomic group. Am J Phys Anthropol, 2010. © 2010 Wiley‐Liss, Inc.