Detection of Biochemical Pathways by Probabilistic Matching of Phyletic Vectors

A phyletic vector, also known as a phyletic (or phylogenetic) pattern, is a binary representation of the presences and absences of orthologous genes in different genomes. Joint occurrence of two or more genes in many genomes results in closely similar binary vectors representing these genes, and this similarity between gene vectors may be used as a measure of functional association between genes. Better understanding of quantitative properties of gene co-occurrences is needed for systematic studies of gene function and evolution. We used the probabilistic iterative algorithm Psi-square to find groups of similar phyletic vectors. An extended Psi-square algorithm, in which pseudocounts are implemented, shows better sensitivity in identifying proteins with known functional links than our earlier hierarchical clustering approach. At the same time, the specificity of inferring functional associations between genes in prokaryotic genomes is strongly dependent on the pathway: phyletic vectors of the genes involved in energy metabolism and in de novo biosynthesis of the essential precursors tend to be lumped together, whereas cellular modules involved in secretion, motility, assembly of cell surfaces, biosynthesis of some coenzymes, and utilization of secondary carbon sources tend to be identified with much greater specificity. It appears that the network of gene coinheritance in prokaryotes contains a giant connected component that encompasses most biosynthetic subsystems, along with a series of more independent modules involved in cell interaction with the environment

Protein Complex Evolution Does Not Involve Extensive Network Rewiring

The formation of proteins into stable protein complexes plays a fundamental role in the operation of the cell. The study of the degree of evolutionary conservation of protein complexes between species and the evolution of protein-protein interactions has been hampered by lack of comprehensive coverage of the high-throughput (HTP) technologies that measure the interactome. We show that new high-throughput datasets on protein co-purification in yeast have a substantially lower false negative rate than previous datasets when compared to known complexes. These datasets are therefore more suitable to estimate the conservation of protein complex membership than hitherto possible. We perform comparative genomics between curated protein complexes from human and the HTP data in Saccharomyces cerevisiae to study the evolution of co-complex memberships. This analysis revealed that out of the 5,960 protein pairs that are part of the same complex in human, 2,216 are absent because both proteins lack an ortholog in S. cerevisiae, while for 1,828 the co-complex membership is disrupted because one of the two proteins lacks an ortholog. For the remaining 1,916 protein pairs, only 10% were never co-purified in the large-scale experiments. This implies a conservation level of co-complex membership of 90% when the genes coding for the protein pairs that participate in the same protein complex are also conserved. We conclude that the evolutionary dynamics of protein complexes are, by and large, not the result of network rewiring (i.e. acquisition or loss of co-complex memberships), but mainly due to genomic acquisition or loss of genes coding for subunits. We thus reveal evidence for the tight interrelation of genomic and network evolution

Tool-use learning by common marmosets (Callithrix jacchus)

One of the most critical and common features of tool use is that the tool essentially functions as a part of the body. This feature is likely rooted in biological features that are shared by tool users. To establish an ideal primate model to explore the neurobiological mechanisms supporting tool-use behaviours, we trained common marmosets, a small New World monkey species that is not usually associated with tool use, to use a rake-shaped tool to retrieve food. Five naive common marmosets were systematically trained to manipulate the tool using a 4-stage, step-by-step protocol. The relative positions of the tool and the food were manipulated, so that the marmosets were required to (1) pull the tool vertically, (2) move the tool horizontally, (3) make an arc to retrieve a food item located behind the tool and (4) retrieve the food item. We found considerable individual differences in tool-use technique; for example, one animal consistently used a unilateral hand movement for all of the steps, whereas the others (n = 4) used both hands to move the tool depending on the location of the food item. After extensive training, all of the marmosets could manipulate the rake-shaped tool, which is reported in this species for the first time. The common marmoset is thus a model primate for such studies. This study sets the stage for future research to examine the biological mechanisms underlying the cognitive ability of tool use at the molecular and genetic levels

Cohesive versus Flexible Evolution of Functional Modules in Eukaryotes

Although functionally related proteins can be reliably predicted from phylogenetic profiles, many functional modules do not seem to evolve cohesively according to case studies and systematic analyses in prokaryotes. In this study we quantify the extent of evolutionary cohesiveness of functional modules in eukaryotes and probe the biological and methodological factors influencing our estimates. We have collected various datasets of protein complexes and pathways in Saccheromyces cerevisiae. We define orthologous groups on 34 eukaryotic genomes and measure the extent of cohesive evolution of sets of orthologous groups of which members constitute a known complex or pathway. Within this framework it appears that most functional modules evolve flexibly rather than cohesively. Even after correcting for uncertain module definitions and potentially problematic orthologous groups, only 46% of pathways and complexes evolve more cohesively than random modules. This flexibility seems partly coupled to the nature of the functional module because biochemical pathways are generally more cohesively evolving than complexes

Chimpanzee Autarky

Background: Economists believe that barter is the ultimate cause of social wealth—and even much of our human culture—yet little is known about the evolution and development of such behavior. It is useful to examine the circumstances under which other species will or will not barter to more fully understand the phenomenon. Chimpanzees (Pan troglodytes) are an interesting test case as they are an intelligent species, closely related to humans, and known to participate in reciprocal interactions and token economies with humans, yet they have not spontaneously developed costly barter. Methodology/Principle Findings: Although chimpanzees do engage in noncostly barter, in which otherwise value-less tokens are exchanged for food, this lack of risk is not typical of human barter. Thus, we systematically examined barter in chimpanzees to ascertain under what circumstances chimpanzees will engage in costly barter of commodities, that is, trading food items for other food items with a human experimenter. We found that chimpanzees do barter, relinquishing lower value items to obtain higher value items (and not the reverse). However, they do not trade in all beneficial situations, maintaining possession of less preferred items when the relative gains they stand to make are small. Conclusions/Significance: Two potential explanations for this puzzling behavior are that chimpanzees lack ownership norms, and thus have limited opportunity to benefit from the gains of trade, and that chimpanzees\u27 risk of defection is sufficiently high that large gains must be imminent to justify the risk. Understanding the conditions that support barter in chimpanzees may increase understanding of situations in which humans, too, do not maximize their gains

A Dual Origin of the Xist Gene from a Protein-Coding Gene and a Set of Transposable Elements

X-chromosome inactivation, which occurs in female eutherian mammals is controlled by a complex X-linked locus termed the X-inactivation center (XIC). Previously it was proposed that genes of the XIC evolved, at least in part, as a result of pseudogenization of protein-coding genes. In this study we show that the key XIC gene Xist, which displays fragmentary homology to a protein-coding gene Lnx3, emerged de novo in early eutherians by integration of mobile elements which gave rise to simple tandem repeats. The Xist gene promoter region and four out of ten exons found in eutherians retain homology to exons of the Lnx3 gene. The remaining six Xist exons including those with simple tandem repeats detectable in their structure have similarity to different transposable elements. Integration of mobile elements into Xist accompanies the overall evolution of the gene and presumably continues in contemporary eutherian species. Additionally we showed that the combination of remnants of protein-coding sequences and mobile elements is not unique to the Xist gene and is found in other XIC genes producing non-coding nuclear RNA

Investigation of the Origin and Spread of a Mammalian Transposable Element Based on Current Sequence Diversity

Almost half the human genome consists of mobile DNA elements, and their analysis is a vital part of understanding the human genome as a whole. Many of these elements are ancient and have persisted in the genome for tens or hundreds of millions of years, providing a window into the evolution of modern mammals. The Golem family have been used as model transposons to highlight computational analyses which can be used to investigate these elements, particularly the use of molecular dating with large transposon families. Whole-genome searches found Golem sequences in 20 mammalian species. Golem A and B subsequences were only found in primates and squirrel. Interestingly, the full-length Golem, found as a few copies in many mammalian genomes, was found abundantly in horse. A phylogenetic profile suggested that Golem originated after the eutherian–metatherian divergence and that the A and B subfamilies originated at a much later date. Molecular dating based on sequence diversity suggests an early age, of 175 Mya, for the origin of the family and that the A and B lineages originated much earlier than expected from their current taxonomic distribution and have subsequently been lost in some lineages. Using publically available data, it is possible to investigate the evolutionary history of transposon families. Determining in which organisms a transposon can be found is often used to date the origin and expansion of the families. However, in this analysis, molecular dating, commonly used for determining the age of gene sequences, has been used, reducing the likelihood of errors from deleted lineages

Extensive Gains and Losses of Olfactory Receptor Genes in Mammalian Evolution

Odor perception in mammals is mediated by a large multigene family of olfactory receptor (OR) genes. The number of OR genes varies extensively among different species of mammals, and most species have a substantial number of pseudogenes. To gain some insight into the evolutionary dynamics of mammalian OR genes, we identified the entire set of OR genes in platypuses, opossums, cows, dogs, rats, and macaques and studied the evolutionary change of the genes together with those of humans and mice. We found that platypuses and primates have <400 functional OR genes while the other species have 800–1,200 functional OR genes. We then estimated the numbers of gains and losses of OR genes for each branch of the phylogenetic tree of mammals. This analysis showed that (i) gene expansion occurred in the placental lineage each time after it diverged from monotremes and from marsupials and (ii) hundreds of gains and losses of OR genes have occurred in an order-specific manner, making the gene repertoires highly variable among different orders. It appears that the number of OR genes is determined primarily by the functional requirement for each species, but once the number reaches the required level, it fluctuates by random duplication and deletion of genes. This fluctuation seems to have been aided by the stochastic nature of OR gene expression

Chemical characterization of oligosaccharides in the milk of six species of New and Old world monkeys

Human and great ape milks contain a diverse array of milk oligosaccharides, but little is known about the milk oligosaccharides of other primates, and how they differ among taxa. Neutral and acidic oligosaccharides were isolated from the milk of three species of Old World or catarrhine monkeys (Cercopithecidae: rhesus macaque (Macaca mulatta), toque macaque (Macaca sinica) and Hamadryas baboon (Papio hamadryas)) and three of New World or platyrrhine monkeys (Cebidae: tufted capuchin (Cebus apella) and Bolivian squirrel monkey (Saimiri boliviensis); Atelidae: mantled howler (Alouatta palliata)). The milks of these species contained 6–8% total sugar, most of which was lactose: the estimated ratio of oligosaccharides to lactose in Old World monkeys (1:4 to 1:6) was greater than in New World monkeys (1:12 to 1:23). The chemical structures of the oligosaccharides were determined mainly by 1H-NMR spectroscopy. Oligosaccharides containing the type II unit (Gal(β1-4)GlcNAc) were found in the milk of the rhesus macaque, toque macaque, Hamadryas baboon and tufted capuchin, but oligosaccharides containing the type I unit (Gal(β1-3)GlcNAc), which have been found in human and many great ape milks, were absent from the milk of all species studied. Oligosaccharides containing Lewis x (Gal(β1-4)[Fuc(α1-3)]GlcNAc) and 3-fucosyl lactose (3-FL, Gal(β1-4)[Fuc(α1-3)]Glc) were found in the milk of the three cercopithecid monkey species, while 2-fucosyl lactose (5'-FL, Fuc(α1-2)Gal(β1-4)Glc) was absent from all species studied. All of these milks contained acidic oligosaccharides that had N-acetylneuraminic acid as part of their structures, but did not contain oligosaccharides that had N-glycolylneuraminic acid, in contrast to the milk or colostrum of great apes which contain both types of acidic oligosaccharides. Two GalNAc-containing oligosaccharides, lactose 3′-O-sulfate and lacto-N-novopentaose I (Gal(β1-3)[Gal(β1-4)GlcNAc(β1-6)]Gal(β1-4)Glc) were found only in the milk of rhesus macaque, hamadryas baboon and tufted capuchin, respectively. Further research is needed to determine the extent to which the milk oligosaccharide patterns observed among these taxa represent wider phylogenetic trends among primates and how much variation occurs among individuals or species

Signs of positive selection of somatic mutations in human cancers detected by EST sequence analysis

BACKGROUND: Carcinogenesis typically involves multiple somatic mutations in caretaker (DNA repair) and gatekeeper (tumor suppressors and oncogenes) genes. Analysis of mutation spectra of the tumor suppressor that is most commonly mutated in human cancers, p53, unexpectedly suggested that somatic evolution of the p53 gene during tumorigenesis is dominated by positive selection for gain of function. This conclusion is supported by accumulating experimental evidence of evolution of new functions of p53 in tumors. These findings prompted a genome-wide analysis of possible positive selection during tumor evolution. METHODS: A comprehensive analysis of probable somatic mutations in the sequences of Expressed Sequence Tags (ESTs) from malignant tumors and normal tissues was performed in order to access the prevalence of positive selection in cancer evolution. For each EST, the numbers of synonymous and non-synonymous substitutions were calculated. In order to identify genes with a signature of positive selection in cancers, these numbers were compared to: i) expected numbers and ii) the numbers for the respective genes in the ESTs from normal tissues. RESULTS: We identified 112 genes with a signature of positive selection in cancers, i.e., a significantly elevated ratio of non-synonymous to synonymous substitutions, in tumors as compared to 37 such genes in an approximately equal-sized EST collection from normal tissues. A substantial fraction of the tumor-specific positive-selection candidates have experimentally demonstrated or strongly predicted links to cancer. CONCLUSION: The results of EST analysis should be interpreted with extreme caution given the noise introduced by sequencing errors and undetected polymorphisms. Furthermore, an inherent limitation of EST analysis is that multiple mutations amenable to statistical analysis can be detected only in relatively highly expressed genes. Nevertheless, the present results suggest that positive selection might affect a substantial number of genes during tumorigenic somatic evolution