CiteULike: Tag evolution

Data and Theory Point to Mainly Additive Genetic Variance for Complex Traits

William Hill — 2008-07-01T10:00:17-00:00

PLoS Genet, Vol. 4, No. 2. (29 February 2008), e1000008.

The relative proportion of additive and non-additive variation for complex traits is important in evolutionary biology, medicine, and agriculture. We address a long-standing controversy and paradox about the contribution of non-additive genetic variation, namely that knowledge about biological pathways and gene networks imply that epistasis is important. Yet empirical data across a range of traits and species imply that most genetic variance is additive. We evaluate the evidence from empirical studies of genetic variance components and find that additive variance typically accounts for over half, and often close to 100%, of the total genetic variance. We present new theoretical results, based upon the distribution of allele frequencies under neutral and other population genetic models, that show why this is the case even if there are non-additive effects at the level of gene action. We conclude that interactions at the level of genes are not likely to generate much interaction at the level of variance.

The evolution of genome compression and genomic novelty in RNA viruses.

Robert Belshaw — 2007-09-07T05:21:32-00:00

Genome Res (4 September 2007)

The genomes of RNA viruses are characterized by their extremely small size and extremely high mutation rates (typically 10 kb and 10(-4)/base/replication cycle, respectively), traits that are thought to be causally linked. One aspect of their small size is the genome compression caused by the use of overlapping genes (where some nucleotides code for two genes). Using a comparative analysis of all known RNA viral species, we show that viruses with larger genomes tend to have less gene overlap. We provide a numerical model to show how a high mutation rate could lead to gene overlap, and we discuss the factors that might explain the observed relationship between gene overlap and genome size. We also propose a model for the evolution of gene overlap based on the co-opting of previously unused ORFs, which gives rise to two types of overlap: (1) the creation of novel genes inside older genes, predominantly via +1 frameshifts, and (2) the incremental increase in overlap between originally contiguous genes, with no frameshift preference. Both types of overlap are viewed as the creation of genomic novelty under pressure for genome compression. Simulations based on our model generate the empirical size distributions of overlaps and explain the observed frameshift preferences. We suggest that RNA viruses are a good model system for the investigation of general evolutionary relationship between genome attributes such as mutational robustness, mutation rate, and size.

Worldwide Human Relationships Inferred from Genome-Wide Patterns of Variation

Jun Li — 2008-02-22T08:51:45-00:00

Science, Vol. 319, No. 5866. (22 February 2008), pp. 1100-1104.

Human genetic diversity is shaped by both demographic and biological factors and has fundamental implications for understanding the genetic basis of diseases. We studied 938 unrelated individuals from 51 populations of the Human Genome Diversity Panel at 650,000 common single-nucleotide polymorphism loci. Individual ancestry and population substructure were detectable with very high resolution. The relationship between haplotype heterozygosity and geography was consistent with the hypothesis of a serial founder effect with a single origin in sub-Saharan Africa. In addition, we observed a pattern of ancestral allele frequency distributions that reflects variation in population dynamics among geographic regions. This data set allows the most comprehensive characterization to date of human genetic variation. 10.1126/science.1153717

Direct Visualization of Horizontal Gene Transfer

Ana Babic — 2008-03-14T05:48:40-00:00

Science, Vol. 319, No. 5869. (14 March 2008), pp. 1533-1536.

Conjugation allows bacteria to acquire genes for antibiotic resistance, novel virulence attributes, and alternative metabolic pathways. Using a fluorescent protein fusion, SeqA-YFP, we have visualized this process in real time and in single cells of Escherichia coli. We found that the F pilus mediates DNA transfer at considerable cell-to-cell distances. Integration of transferred DNA by recombination occurred in up to 96% of recipients; in the remaining cells, the transferred DNA was fully degraded by the RecBCD helicase/nuclease. The acquired integrated DNA was tracked through successive replication rounds and was found to occasionally split and segregate with different chromosomes, leading to the inheritance of different gene clusters within the cell lineage. The incidence of DNA splitting corresponds to about one crossover per cell generation. 10.1126/science.1153498

Transcription Factor Substitution during the Evolution of Fungal Ribosome Regulation

Herve Hogues — 2008-03-20T13:23:27-00:00

Molecular Cell, Vol. 29, No. 5. (14 March 2008), pp. 552-562.

Summary Coordinated ribosomal protein (RP) gene expression is crucial for cellular viability, but the transcriptional network controlling this regulon has only been well characterized in the yeast Saccharomyces cerevisiae. We have used whole-genome transcriptional and location profiling to establish that, in Candida albicans, the RP regulon is controlled by the Myb domain protein Tbf1 working in conjunction with Cbf1. These two factors bind both the promoters of RP genes and the rDNA locus; Tbf1 activates transcription at these loci and is essential. Orthologs of Tbf1 bind TTAGGG telomeric repeats in most eukaryotes, and TTAGGG cis-elements are present upstream of RP genes in plants and fungi, suggesting that Tbf1 was involved in both functions in ancestral eukaryotes. In all Hemiascomycetes, Rap1 substituted Tbf1 at telomeres and, in the S. cerevisiae lineage, this substitution also occurred independently at RP genes, illustrating the extreme adaptability and flexibility of transcriptional regulatory networks.

The evolution of human influenza A viruses from 1999 to 2006 - a complete genome study

Karoline Bragstad — 2008-03-07T17:03:37-00:00

Virology Journal, Vol. 5 (07 March 2008), 40.

Rates of evolutionary change in viruses: patterns and determinants

Siobain Duffy — 2008-03-19T16:33:41-00:00

Nature Reviews Genetics, Vol. 9, No. 4. (04 March 2008), pp. 267-276.

Design of protein function leaps by directed domain interface evolution

Jin Huang — 2008-04-30T19:38:26-00:00

Proceedings of the National Academy of Sciences (29 April 2008), 0801097105.

Most natural proteins performing sophisticated tasks contain multiple domains where an active site is located at the domain interface. Comparative structural analyses suggest that major leaps in protein function occur through gene recombination events that connect two or more protein domains to generate a new active site, frequently occurring at the newly created domain interface. However, such functional leaps by combination of unrelated domains have not been directly demonstrated. Here we show that highly specific and complex protein functions can be generated by joining a low-affinity peptide-binding domain with a functionally inert second domain and subsequently optimizing the domain interface. These directed evolution processes dramatically enhanced both affinity and specificity to a level unattainable with a single domain, corresponding to >500-fold and >2,000-fold increases of affinity and specificity, respectively. An x-ray crystal structure revealed that the resulting "affinity clamp" had clamshell architecture as designed, with large additional binding surface contributed by the second domain. The affinity clamps having a single-nanomolar dissociation constant outperformed a monoclonal antibody in immunochemical applications. This work establishes evolutionary paths from isolated domains with primitive function to multidomain proteins with sophisticated function and introduces a new protein-engineering concept that allows for the generation of highly functional affinity reagents to a predefined target. The prevalence and variety of natural interaction domains suggest that numerous new functions can be designed by using directed domain interface evolution. 10.1073/pnas.0801097105

Life-history traits drive the evolutionary rates of mammalian coding and noncoding genomic elements

Sergey Nikolaev — 2007-12-12T10:23:23-00:00

Proceedings of the National Academy of Sciences (11 December 2007), 0705658104.

A comprehensive phylogenetic framework is indispensable for investigating the evolution of genomic features in mammals as a whole, and particularly in humans. Using the ENCODE sequence data, we estimated mammalian neutral evolutionary rates and selective pressures acting on conserved coding and noncoding elements. We show that neutral evolutionary rates can be explained by the generation time (GT) hypothesis. Accordingly, primates (especially humans), having longer GTs than other mammals, display slower rates of neutral evolution. The evolution of constrained elements, particularly of nonsynonymous sites, is in agreement with the expectations of the nearly neutral theory of molecular evolution. We show that rates of nonsynonymous substitutions (dN) depend on the population size of a species. The results are robust to the exclusion of hypermutable CpG prone sites. The average rate of evolution in conserved noncoding sequences (CNCs) is 1.7 times higher than in nonsynonymous sites. Despite this, CNCs evolve at similar or even lower rates than nonsynonymous sites in the majority of basal branches of the eutherian tree. This observation could be the result of an overall gradual or, alternatively, lineage-specific relaxation of CNCs. The latter hypothesis was supported by the finding that 3 of the 20 longest CNCs displayed significant relaxation of individual branches. This observation may explain why the evolution of CNCs fits the expectations of the nearly neutral theory less well than the evolution of nonsynonymous sites. 10.1073/pnas.0705658104

Evolution: A gene is born

Tanita Casci — 2008-05-17T12:26:02-00:00

Nature Reviews Genetics, Vol. 9, No. 6., pp. 415-415.

Evolution of Function in the “Two Dinucleotide Binding Domains” Flavoproteins

Sunil Ojha — 2007-07-20T17:32:51-00:00

PLoS Computational Biology, Vol. 3, No. 7. (1 July 2007), e121.

Structural and biochemical constraints force some segments of proteins to evolve more slowly than others, often allowing identification of conserved structural or sequence motifs that can be associated with substrate binding properties, chemical mechanisms, and molecular functions. We have assessed the functional and structural constraints imposed by cofactors on the evolution of new functions in a superfamily of flavoproteins characterized by two-dinucleotide binding domains, the “two dinucleotide binding domains” flavoproteins (tDBDF) superfamily. Although these enzymes catalyze many different types of oxidation/reduction reactions, each is initiated by a stereospecific hydride transfer reaction between two cofactors, a pyridine nucleotide and flavin adenine dinucleotide (FAD). Sequence and structural analysis of more than 1,600 members of the superfamily reveals new members and identifies details of the evolutionary connections among them. Our analysis shows that in all of the highly divergent families within the superfamily, these cofactors adopt a conserved configuration optimal for stereospecific hydride transfer that is stabilized by specific interactions with amino acids from several motifs distributed among both dinucleotide binding domains. The conservation of cofactor configuration in the active site restricts the pyridine nucleotide to interact with FAD from the re-side, limiting the flow of electrons from the re-side to the si-side. This directionality of electron flow constrains interactions with the different partner proteins of different families to occur on the same face of the cofactor binding domains. As a result, superimposing the structures of tDBDFs aligns not only these interacting proteins, but also their constituent electron acceptors, including heme and iron-sulfur clusters. Thus, not only are specific aspects of the cofactor-directed chemical mechanism conserved across the superfamily, the constraints they impose are manifested in the mode of protein–protein interactions. Overlaid on this foundation of conserved interactions, nature has conscripted different protein partners to serve as electron acceptors, thereby generating diversification of function across the superfamily.

Genetic Association Mapping via Evolution-Based Clustering of Haplotypes

Ioanna Tachmazidou — 2007-08-02T15:30:41-00:00

PLoS Genetics, Vol. 3, No. 7. (1 July 2007), e111.

Multilocus analysis of single nucleotide polymorphism haplotypes is a promising approach to dissecting the genetic basis of complex diseases. We propose a coalescent-based model for association mapping that potentially increases the power to detect disease-susceptibility variants in genetic association studies. The approach uses Bayesian partition modelling to cluster haplotypes with similar disease risks by exploiting evolutionary information. We focus on candidate gene regions with densely spaced markers and model chromosomal segments in high linkage disequilibrium therein assuming a perfect phylogeny. To make this assumption more realistic, we split the chromosomal region of interest into sub-regions or windows of high linkage disequilibrium. The haplotype space is then partitioned into disjoint clusters, within which the phenotype–haplotype association is assumed to be the same. For example, in case-control studies, we expect chromosomal segments bearing the causal variant on a common ancestral background to be more frequent among cases than controls, giving rise to two separate haplotype clusters. The novelty of our approach arises from the fact that the distance used for clustering haplotypes has an evolutionary interpretation, as haplotypes are clustered according to the time to their most recent common ancestor. Our approach is fully Bayesian and we develop a Markov Chain Monte Carlo algorithm to sample efficiently over the space of possible partitions. We compare the proposed approach to both single-marker analyses and recently proposed multi-marker methods and show that the Bayesian partition modelling performs similarly in localizing the causal allele while yielding lower false-positive rates. Also, the method is computationally quicker than other multi-marker approaches. We present an application to real genotype data from the CYP2D6 gene region, which has a confirmed role in drug metabolism, where we succeed in mapping the location of the susceptibility variant within a small error.

New Taxonomy and the Origin of Species

Shai Meiri — 2007-08-28T16:42:20-00:00

PLoS Biology, Vol. 5, No. 7. (1 July 2007), e194.

A Comprehensive Phylogeny of Beetles Reveals the Evolutionary Origins of a Superradiation

Toby Hunt — 2007-12-21T09:46:44-00:00

Science, Vol. 318, No. 5858. (21 December 2007), pp. 1913-1916.

Beetles represent almost one-fourth of all described species, and knowledge about their relationships and evolution adds to our understanding of biodiversity. We performed a comprehensive phylogenetic analysis of Coleoptera inferred from three genes and nearly 1900 species, representing more than 80% of the world's recognized beetle families. We defined basal relationships in the Polyphaga supergroup, which contains over 300,000 species, and established five families as the earliest branching lineages. By dating the phylogeny, we found that the success of beetles is explained neither by exceptional net diversification rates nor by a predominant role of herbivory and the Cretaceous rise of angiosperms. Instead, the pre-Cretaceous origin of more than 100 present-day lineages suggests that beetle species richness is due to high survival of lineages and sustained diversification in a variety of niches. 10.1126/science.1146954

Frequent Gain and Loss of Functional Transcription Factor Binding Sites

Scott Doniger — 2007-05-26T03:59:06-00:00

PLoS Computational Biology, Vol. 3, No. 5. (1 May 2007), e99.

Cis-regulatory sequences are not always conserved across species. Divergence within cis-regulatory sequences may result from the evolution of species-specific patterns of gene expression or the flexible nature of the cis-regulatory code. The identification of functional divergence in cis-regulatory sequences is therefore important for both understanding the role of gene regulation in evolution and annotating regulatory elements. We have developed an evolutionary model to detect the loss of constraint on individual transcription factor binding sites (TFBSs). We find that a significant fraction of functionally constrained binding sites have been lost in a lineage-specific manner among three closely related yeast species. Binding site loss has previously been explained by turnover, where the concurrent gain and loss of a binding site maintains gene regulation. We estimate that nearly half of all loss events cannot be explained by binding site turnover. Recreating the mutations that led to binding site loss confirms that these sequence changes affect gene expression in some cases. We also estimate that there is a high rate of binding site gain, as more than half of experimentally identified S. cerevisiae binding sites are not conserved across species. The frequent gain and loss of TFBSs implies that cis-regulatory sequences are labile and, in the absence of turnover, may contribute to species-specific patterns of gene expression.

Protein Design by Directed Evolution

Christian Jackel — 2008-05-08T08:48:35-00:00

Annual Review of Biophysics, Vol. 37, No. 1. (2008), pp. 153-173.

While nature evolved polypeptides over billions of years, protein design by evolutionary mimicry is progressing at a far more rapid pace. The mutation, selection, and amplification steps of the evolutionary cycle may be imitated in the laboratory using existing proteins, or molecules created de novo from random sequence space, as starting templates. However, the astronomically large number of possible polypeptide sequences remains an obstacle to identifying and isolating functionally interesting variants. Intelligently designed libraries and improved search techniques are consequently important for future advances. In this regard, combining experimental and computational methods holds particular promise for the creation of tailored protein receptors and catalysts for tasks unimagined by nature.

Quantifying social group evolution

Gergely Palla — 2007-04-04T18:39:56-00:00

Nature, Vol. 446, No. 7136. (5 April 2007), pp. 664-667.

Molecular and Genomic Data Identify the Closest Living Relative of Primates

Jan Janecka — 2007-11-02T21:42:33-00:00

Science, Vol. 318, No. 5851. (2 November 2007), pp. 792-794.

A full understanding of primate morphological and genomic evolution requires the identification of their closest living relative. In order to resolve the ancestral relationships among primates and their closest relatives, we searched multispecies genome alignments for phylogenetically informative rare genomic changes within the superordinal group Euarchonta, which includes the orders Primates, Dermoptera (colugos), and Scandentia (treeshrews). We also constructed phylogenetic trees from 14 kilobases of nuclear genes for representatives from most major primate lineages, both extant colugos, and multiple treeshrews, including the pentail treeshrew, Ptilocercus lowii, the only living member of the family Ptilocercidae. A relaxed molecular clock analysis including Ptilocercus suggests that treeshrews arose approximately 63 million years ago. Our data show that colugos are the closest living relatives of primates and indicate that their divergence occurred in the Cretaceous. 10.1126/science.1147555

Quaternary Structure Constraints on Evolutionary Sequence Divergence

Fornasari — 2007-02-04T11:19:01-00:00

Molecular Biology and Evolution, Vol. 24, No. 2. (February 2007), pp. 349-351.

Empirical fitness landscapes reveal accessible evolutionary paths

Frank Poelwijk — 2007-01-25T17:08:44-00:00

Nature, Vol. 445, No. 7126. (25 January 2007), pp. 383-386.

Functional evolution of the p53 regulatory network through its target response elements

Anil Jegga — 2008-01-14T05:28:21-00:00

Proceedings of the National Academy of Sciences (10 January 2008), 0704694105.

Transcriptional network evolution is central to the development of complex biological systems. Networks can evolve through variation of master regulators and/or by changes in regulation of genes within networks. To gain insight into meaningful evolutionary differences in large networks, it is essential to address the functional consequences of sequence differences in response elements (REs) targeted by transcription factors. Using a combination of custom bioinformatics and multispecies alignment of promoter regions, we investigated the functional evolution of REs in terms of responsiveness to the sequence-specific transcription factor p53, a tumor suppressor and master regulator of stress responses. We identified REs orthologous to known p53 targets in human and rodent cells or alternatively REs related to the established p53 consensus. The orthologous REs were assigned p53 transactivation capabilities based on rules determined from model systems, and a functional heat map was developed to visually summarize conservation of sequence and relative level of responsiveness to p53 for 47 REs in 14 species. Individual REs exhibited marked differences in transactivation potentials and widespread evolutionary turnover. Functional differences were often not predicted from consensus sequence evaluations. Of the established human p53 REs analyzed, 91% had sequence conservation in at least one nonprimate species compared with 67.5% for functional conservation. Surprisingly, there was almost no conservation of functional REs for genes involved in DNA metabolism or repair between humans and rodents, suggesting important differences in p53 stress responses and cancer development. 10.1073/pnas.0704694105

Phylogeny-Aware Gap Placement Prevents Errors in Sequence Alignment and Evolutionary Analysis

Ari Loytynoja — 2008-06-20T03:07:52-00:00

Science, Vol. 320, No. 5883. (20 June 2008), pp. 1632-1635.

Genetic sequence alignment is the basis of many evolutionary and comparative studies, and errors in alignments lead to errors in the interpretation of evolutionary information in genomes. Traditional multiple sequence alignment methods disregard the phylogenetic implications of gap patterns that they create and infer systematically biased alignments with excess deletions and substitutions, too few insertions, and implausible insertion-deletion-event histories. We present a method that prevents these systematic errors by recognizing insertions and deletions as distinct evolutionary events. We show theoretically and practically that this improves the quality of sequence alignments and downstream analyses over a wide range of realistic alignment problems. These results suggest that insertions and sequence turnover are more common than is currently thought and challenge the conventional picture of sequence evolution and mechanisms of functional and structural changes. 10.1126/science.1158395

A First-Principles Model of Early Evolution: Emergence of Gene Families, Species, and Preferred Protein Folds

Konstantin Zeldovich — 2007-07-13T18:27:36-00:00

PLoS Computational Biology, Vol. 3, No. 7. (1 July 2007), e139.

In this work we develop a microscopic physical model of early evolution where phenotype—organism life expectancy—is directly related to genotype—the stability of its proteins in their native conformations—which can be determined exactly in the model. Simulating the model on a computer, we consistently observe the “Big Bang” scenario whereby exponential population growth ensues as soon as favorable sequence–structure combinations (precursors of stable proteins) are discovered. Upon that, random diversity of the structural space abruptly collapses into a small set of preferred proteins. We observe that protein folds remain stable and abundant in the population at timescales much greater than mutation or organism lifetime, and the distribution of the lifetimes of dominant folds in a population approximately follows a power law. The separation of evolutionary timescales between discovery of new folds and generation of new sequences gives rise to emergence of protein families and superfamilies whose sizes are power-law distributed, closely matching the same distributions for real proteins. On the population level we observe emergence of species—subpopulations that carry similar genomes. Further, we present a simple theory that relates stability of evolving proteins to the sizes of emerging genomes. Together, these results provide a microscopic first-principles picture of how first-gene families developed in the course of early evolution.

From Genotype to Phenotype: Systems Biology Meets Natural Variation

Philip Benfey — 2008-04-24T22:05:03-00:00

Science, Vol. 320, No. 5875. (25 April 2008), pp. 495-497.

The promise that came with genome sequencing was that we would soon know what genes do, particularly genes involved in human diseases and those of importance to agriculture. We now have the full genomic sequence of human, chimpanzee, mouse, chicken, dog, worm, fly, rice, and cress, as well as those for a wide variety of other species, and yet we still have a lot of trouble figuring out what genes do. Mapping genes to their function is called the "genotype-to-phenotype problem," where phenotype is whatever is changed in the organism when a gene's function is altered. 10.1126/science.1153716

Evolutionary plasticity of developmental gene regulatory network architecture

Veronica Hinman — 2007-11-28T06:17:29-00:00

Proceedings of the National Academy of Sciences (27 November 2007), 0709994104.

Sea stars and sea urchins evolved from a last common ancestor that lived at the end of the Cambrian, approximately half a billion years ago. In a previous comparative study of the gene regulatory networks (GRNs) that embody the genomic program for embryogenesis in these animals, we discovered an almost perfectly conserved five-gene network subcircuit required for endoderm specification. We show here that the GRN structure upstream and downstream of the conserved network kernel has, by contrast, diverged extensively. Mesoderm specification is accomplished quite differently; the DeltaNotch signaling system is used in radically distinct ways; and various regulatory genes have been coopted to different functions. The conservation of the conserved kernel is thus the more remarkable. The results indicate types of network linkage subject to evolutionary change. An emergent theme is that subcircuit design may be preserved even while the identity of genes performing given roles changes because of alteration in their cis-regulatory control systems. 10.1073/pnas.0709994104

Genome Analysis of Minibacterium massiliensis Highlights the Convergent Evolution of Water-Living Bacteria

Stéphane Audic — 2007-09-03T14:15:57-00:00

PLoS Genetics, Vol. 3, No. 8. (1 August 2007), e138.

Filtration usually eliminates water-living bacteria. Here, we report on the complete genome sequence of Minibacterium massiliensis, a β-proteobacteria that was recovered from 0.22-μm filtered water used for patients in the hospital. The unexpectedly large 4,110,251-nucleotide genome sequence of M. massiliensis was determined using the traditional shotgun sequencing approach. Bioinformatic analyses shows that the M. massiliensis genome sequence illustrates characteristic features of water-living bacteria, including overrepresentation of genes encoding transporters and transcription regulators. Phylogenomic analysis based on the gene content of available bacterial genome sequences displays a congruent evolution of water-living bacteria from various taxonomic origins, principally for genes involved in energy production and conversion, cell division, chromosome partitioning, and lipid metabolism. This phylogenomic clustering partially results from lateral gene transfer, which appears to be more frequent in water than in other environments. The M. massiliensis genome analyses strongly suggest that water-living bacteria are a common source for genes involved in heavy-metal resistance, antibiotics resistance, and virulence factors.

BLOSUM62 miscalculations improve search performance

Mark Styczynski — 2008-03-09T04:13:09-00:00

Nature Biotechnology, Vol. 26, No. 3., pp. 274-275.

Toward Resolving the Eukaryotic Tree: The Phylogenetic Positions of Jakobids and Cercozoans

Naiara Rodriguez-Ezpeleta — 2007-08-28T03:01:11-00:00

Current Biology, Vol. 17, No. 16. (21 August 2007), pp. 1420-1425.

Summary Resolving the global phylogeny of eukaryotes has proven to be challenging. Among the eukaryotic groups of uncertain phylogenetic position are jakobids, a group of bacterivorous flagellates that possess the most bacteria-like mitochondrial genomes known and . Jakobids share several ultrastructural features with malawimonads and an assemblage of anaerobic protists (e.g., diplomonads and oxymonads) and . These lineages together with Euglenozoa and Heterolobosea have collectively been designated "excavates" . However, published molecular phylogenies based on the sequences of nuclear rRNAs , and and up to six nucleus-encoded proteins , and do not provide convincing support for the monophyly of excavates, nor do they uncover their relationship to other major eukaryotic groups , , , , and . Here, we report the first large-scale eukaryotic phylogeny, inferred from 143 nucleus-encoded proteins comprising 31,604 amino acid positions, that includes jakobids, malawimonads and cercozoans . We obtain compelling support for the monophyly of jakobids, Euglenozoa plus Heterolobosea (JEH group), and for the association of cercozoans with stramenopiles plus alveolates. Furthermore, we observe a sister-group relationship between the JEH group and malawimonads after removing fast-evolving species from the dataset. We discuss the implications of these results for the concept of "excavates" and for the elucidation of eukaryotic phylogeny in general.

Efficient evolution

Daniel Evanko — 2007-03-31T18:47:36-00:00

Nature Methods, Vol. 4, No. 4., pp. 300-300.

Evolution of protein domain promiscuity in eukaryotes

Malay Basu — 2008-02-11T22:17:34-00:00

Genome Res. (29 January 2008), gr.6943508.

Numerous eukaryotic proteins contain multiple domains. Certain domains show a tendency to occur in diverse domain architectures and can be considered "promiscuous." These promiscuous domains are, typically, involved in proteinprotein interactions and play crucial roles in interaction networks, particularly those that contribute to signal transduction. A systematic comparative-genomic analysis of promiscuous domains in eukaryotes is described. Two quantitative measures of domain promiscuity are introduced and applied to the analysis of 28 genomes of diverse eukaryotes. Altogether, 215 domains are identified as strongly promiscuous. The fraction of promiscuous domains in animals is shown to be significantly greater than that in fungi or plants. Evolutionary reconstructions indicate that domain promiscuity is a volatile, relatively fast-changing feature of eukaryotic proteins, with few domains remaining promiscuous throughout the evolution of eukaryotes. Some domains appear to have attained promiscuity independently in different lineages, for example, animals and plants. It is proposed that promiscuous domains persist within a relatively small pool of evolutionarily stable domain combinations from which numerous rare architectures emerge during evolution. Domain promiscuity positively correlates with the number of experimentally detected domain interactions and with the strength of purifying selection affecting a domain. Thus, evolution of promiscuous domains seems to be constrained by the diversity of their interaction partners. The set of promiscuous domains is enriched for domains mediating proteinprotein interactions that are involved in various forms of signal transduction, especially in the ubiquitin system and in chromatin. Thus, a limited repertoire of promiscuous domains makes a major contribution to the diversity and evolvability of eukaryotic proteomes and signaling networks. 10.1101/gr.6943508

Evolution of genes and genomes on the Drosophila phylogeny

2007-11-07T19:25:43-00:00

Nature, Vol. 450, No. 7167. (November 2007), pp. 203-218.

Evolutionary models for formation of network motifs and modularity in the Saccharomyces transcription factor network.

JJ Ward — 2007-11-05T11:12:10-00:00

PLoS Comput Biol, Vol. 3, No. 10. (26 October 2007), pp. 1993-2002.

Many natural and artificial networks contain overrepresented subgraphs, which have been termed network motifs. In this article, we investigate the processes that led to the formation of the two most common network motifs in eukaryote transcription factor networks: the bi-fan motif and the feed-forward loop. Around 100 million y ago, the common ancestor of the Saccharomyces clade underwent a whole-genome duplication event. The simultaneous duplication of the genes created by this event enabled the origin of many network motifs to be established. The data suggest that there are two primary mechanisms that are involved in motif formation. The first mechanism, enabled by the substantial plasticity in promoter regions, is rewiring of connections as a result of positive environmental selection. The second is duplication of transcription factors, which is also shown to be involved in the formation of intermediate-scale network modularity. These two evolutionary processes are complementary, with the pre-existence of network motifs enabling duplicated transcription factors to bind different targets despite structural constraints on their DNA-binding specificities. This process may facilitate the creation of novel expression states and the increases in regulatory complexity associated with higher eukaryotes.

Distinguishing structural and functional restraints in evolution in order to identify interaction sites.

V Chelliah — 2005-10-10T09:30:09-00:00

J Mol Biol, Vol. 342, No. 5. (1 October 2004), pp. 1487-1504.

Structural genomics projects are producing many three-dimensional structures of proteins that have been identified only from their gene sequences. It is therefore important to develop computational methods that will predict sites involved in productive intermolecular interactions that might give clues about functions. Techniques based on evolutionary conservation of amino acids have the advantage over physiochemical methods in that they are more general. However, the majority of techniques neither use all available structural and sequence information, nor are able to distinguish between evolutionary restraints that arise from the need to maintain structure and those that arise from function. Three methods to identify evolutionary restraints on protein sequence and structure are described here. The first identifies those residues that have a higher degree of conservation than expected: this is achieved by comparing for each amino acid position the sequence conservation observed in the homologous family of proteins with the degree of conservation predicted on the basis of amino acid type and local environment. The second uses information theory to identify those positions where environment-specific substitution tables make poor predictions of the overall amino acid substitution pattern. The third method identifies those residues that have highly conserved positions when three-dimensional structures of proteins in a homologous family are superposed. The scores derived from these methods are mapped onto the protein three-dimensional structures and contoured, allowing identification clusters of residues with strong evolutionary restraints that are sites of interaction in proteins involved in a variety of functions. Our method differs from other published techniques by making use of structural information to identify restraints that arise from the structure of the protein and differentiating these restraints from others that derive from intermolecular interactions that mediate functions in the whole organism.

Is evolvability evolvable?

Massimo Pigliucci — 2007-12-17T10:38:56-00:00

Nat Rev Genet (4 December 2007)

In recent years, biologists have increasingly been asking whether the ability to evolve - the evolvability - of biological systems, itself evolves, and whether this phenomenon is the result of natural selection or a by-product of other evolutionary processes. The concept of evolvability, and the increasing theoretical and empirical literature that refers to it, may constitute one of several pillars on which an extended evolutionary synthesis will take shape during the next few years, although much work remains to be done on how evolvability comes about.

Unequal evolutionary conservation of human protein interactions in interologous networks

Kevin Brown — 2007-05-30T19:30:06-00:00

Genome Biology, Vol. 8 (29 May 2007), R95.

Mechanistic approaches to the study of evolution: the functional synthesis

Antony Dean — 2007-08-18T01:43:38-00:00

Nature Reviews Genetics, Vol. 8, No. 9., pp. 675-688.

Varying environments can speed up evolution

Nadav Kashtan — 2007-08-16T08:29:49-00:00

PNAS (14 August 2007), 0611630104.

Edited by Curtis G. Callan, Jr., Princeton University, Princeton, NJ, and approved June 19, 2007 (received for review December 28, 2006)Simulations of biological evolution, in which computers are used to evolve systems toward a goal, often require many generations to achieve even simple goals. It is therefore of interest to look for generic ways, compatible with natural conditions, in which evolution in simulations can be speeded. Here, we study the impact of temporally varying goals on the speed of evolution, defined as the number of generations needed for an initially random population to achieve a given goal. Using computer simulations, we find that evolution toward goals that change over time can, in certain cases, dramatically speed up evolution compared with evolution toward a fixed goal. The highest speedup is found under modularly varying goals, in which goals change over time such that each new goal shares some of the subproblems with the previous goal. The speedup increases with the complexity of the goal: the harder the problem, the larger the speedup. Modularly varying goals seem to push populations away from local fitness maxima, and guide them toward evolvable and modular solutions. This study suggests that varying environments might significantly contribute to the speed of natural evolution. In addition, it suggests a way to accelerate optimization algorithms and improve evolutionary approaches in engineering. 10.1073/pnas.0611630104

Viral Evolution in the Genomic Age

Edward Holmes — 2007-10-02T19:24:33-00:00

PLoS Biology, Vol. 5, No. 10. (1 October 2007), e278.

Understanding the Evolutionary Fate of Finite Populations: The Dynamics of Mutational Effects

Olin Silander — 2007-04-03T18:58:33-00:00

PLoS Biology, Vol. 5, No. 4. (1 April 2007), e94.

The most consistent result in more than two decades of experimental evolution is that the fitness of populations adapting to a constant environment does not increase indefinitely, but reaches a plateau. Using experimental evolution with bacteriophage, we show here that the converse is also true. In populations small enough such that drift overwhelms selection and causes fitness to decrease, fitness declines down to a plateau. We demonstrate theoretically that both of these phenomena must be due either to changes in the ratio of beneficial to deleterious mutations, the size of mutational effects, or both. We use mutation accumulation experiments and molecular data from experimental evolution to show that the most significant change in mutational effects is a drastic increase in the rate of beneficial mutation as fitness decreases. In contrast, the size of mutational effects changes little even as organismal fitness changes over several orders of magnitude. These findings have significant implications for the dynamics of adaptation.

Morphological evolution through multiple cis-regulatory mutations at a single gene

Alistair Mcgregor — 2007-07-17T11:11:14-00:00

Nature (15 July 2007)

Evolution at the system level: the natural history of protein interaction networks

Michael Stumpf — 2007-05-08T10:42:06-00:00

Trends in Ecology & Evolution, Vol. In Press, Corrected Proof

Recent work leading to new insights into the molecular architecture underlying complex cellular phenotypes enables researchers to investigate evolutionary processes in unprecedented detail. Protein interaction network data, which are now available for an increasing number of species, promise new insights and there have been many recent studies investigating evolutionary aspects of these interaction networks, from mathematical studies of growing networks to detailed phylogenetic surveys of proteins in their interaction network context. Here, we review the spectrum of such approaches, and assess issues associated with analyzing such data from an evolutionary perspective. Currently, such analyses are statistically challenging, but could link present initiatives in systems biology with results and methodologies that have developed in evolutionary biology over the past 60 years.

Functional Architecture and Evolution of Transcriptional Elements That Drive Gene Coexpression

Christopher Brown — 2007-09-14T17:12:44-00:00

Science, Vol. 317, No. 5844. (14 September 2007), pp. 1557-1560.

Transcriptional coexpression of interacting gene products is required for complex molecular processes; however, the function and evolution of cis-regulatory elements that orchestrate coexpression remain largely unexplored. We mutagenized 19 regulatory elements that drive coexpression of Ciona muscle genes and obtained quantitative estimates of the cis-regulatory activity of the 77 motifs that comprise these elements. We found that individual motif activity ranges broadly within and among elements, and among different instantiations of the same motif type. The activity of orthologous motifs is strongly constrained, although motif arrangement, type, and activity vary greatly among the elements of different co-regulated genes. Thus, the syntactical rules governing this regulatory function are flexible but become highly constrained evolutionarily once they are established in a particular element. 10.1126/science.1145893

The evolutionary dynamics of the Saccharomyces cerevisiae protein interaction network after duplication

Aviva Presser — 2008-01-17T08:38:46-00:00

Proceedings of the National Academy of Sciences (16 January 2008), 0707293105.

Gene duplication is an important mechanism in the evolution of protein interaction networks. Duplications are followed by the gain and loss of interactions, rewiring the network at some unknown rate. Because rewiring is likely to change the distribution of network motifs within the duplicated interaction set, it should be possible to study network rewiring by tracking the evolution of these motifs. We have developed a mathematical framework that, together with duplication data from comparative genomic and proteomic studies, allows us to infer the connectivity of the preduplication network and the changes in connectivity over time. We focused on the whole-genome duplication (WGD) event in Saccharomyces cerevisiae. The model allowed us to predict the frequency of intergene interaction before WGD and the post duplication probabilities of interaction gain and loss. We find that the predicted frequency of self-interactions in the preduplication network is significantly higher than that observed in today's network. This could suggest a structural difference between the modern and ancestral networks, preferential addition or retention of interactions between ohnologs, or selective pressure to preserve duplicates of self-interacting proteins. 10.1073/pnas.0707293105

False occurrences of functional motifs in protein sequences highlight evolutionary constraints

Allegra Via — 2007-03-02T13:02:07-00:00

BMC Bioinformatics, Vol. 8 (01 March 2007), 68.

Modeling the Evolution of Protein Domain Architectures Using Maximum Parsimony

Jessica Fong — 2007-01-25T03:25:14-00:00

Journal of Molecular Biology, Vol. 366, No. 1. (9 February 2007), pp. 307-315.

Domains are basic evolutionary units of proteins and most proteins have more than one domain. Advances in domain modeling and collection are making it possible to annotate a large fraction of known protein sequences by a linear ordering of their domains, yielding their architecture. Protein domain architectures link evolutionarily related proteins and underscore their shared functions. Here, we attempt to better understand this association by identifying the evolutionary pathways by which extant architectures may have evolved. We propose a model of evolution in which architectures arise through rearrangements of inferred precursor architectures and acquisition of new domains. These pathways are ranked using a parsimony principle, whereby scenarios requiring the fewest number of independent recombination events, namely fission and fusion operations, are assumed to be more likely. Using a data set of domain architectures present in 159 proteomes that represent all three major branches of the tree of life allows us to estimate the history of over 85% of all architectures in the sequence database. We find that the distribution of rearrangement classes is robust with respect to alternative parsimony rules for inferring the presence of precursor architectures in ancestral species. Analyzing the most parsimonious pathways, we find 87% of architectures to gain complexity over time through simple changes, among which fusion events account for 5.6 times as many architectures as fission. Our results may be used to compute domain architecture similarities, for example, based on the number of historical recombination events separating them. Domain architecture "neighbors" identified in this way may lead to new insights about the evolution of protein function.

Compensatory Evolution Reveals Functional Interactions between Ribosomal Proteins S12, L14 and L19

Sophie Maisnier-Patin — 2007-03-19T12:50:44-00:00

Journal of Molecular Biology, Vol. 366, No. 1. (9 February 2007), pp. 207-215.

Certain mutations in S12, a ribosomal protein involved in translation elongation rate and translation accuracy, confer resistance to the aminoglycoside streptomycin. Previously we showed in Salmonella typhimurium that the fitness cost, i.e. reduced growth rate, due to the amino acid substitution K42N in S12 could be compensated by at least 35 different mutations located in the ribosomal proteins S4, S5 and L19. Here, we have characterized in vivo the fitness, translation speed and translation accuracy of four different L19 mutants. When separated from the resistance mutation located in S12, the three different compensatory amino acid substitutions in L19 at position 40 (Q40H, Q40L and Q40R) caused a decrease in fitness while the G104A change had no effect on bacterial growth. The rate of protein synthesis was unaffected or increased by the mutations at position 40 and the level of read-through of a UGA nonsense codon was increased in vivo, indicating a loss of translational accuracy. The mutations in L19 increased sensitivity to aminoglycosides active at the A-site, further indicating a perturbation of the decoding step. These phenotypes are similar to those of the classical S4 and S5 ram (ribosomal ambiguity) mutants. By evolving low-fitness L19 mutants by serial passage, we showed that the fitness cost conferred by the L19 mutations could be compensated by additional mutations in the ribosomal protein L19 itself, in S12 and in L14, a protein located close to L19. Our results reveal a novel functional role for the 50 S ribosomal protein L19 during protein synthesis, supporting published structural data suggesting that the interaction of L14 and L19 with 16 S rRNA could influence function of the 30 S subunit. Moreover, our study demonstrates how compensatory fitness-evolution can be used to discover new molecular functions of ribosomal proteins.

The Hill–Robertson effect: evolutionary consequences of weak selection and linkage in finite populations

JM Comeron — 2007-09-20T16:52:30-00:00

Heredity, Vol. aop, No. current.

Epistasis between deleterious mutations and the evolution of recombination

Roger Kouyos — 2007-03-19T09:44:31-00:00

Trends in Ecology & Evolution, Vol. In Press, Corrected Proof

Epistasis and the evolution of recombination are closely intertwined: epistasis generates linkage disequilibria (i.e. statistical associations between alleles), whereas recombination breaks them up. The mutational deterministic hypothesis (MDH) states that high recombination rates are maintained because the breaking up of linkage disequilibria generated by negative epistasis enables more efficient purging of deleterious mutations. However, recent theoretical and experimental work challenges the MDH. Experimental evidence suggests that negative epistasis, required by the MDH, is relatively uncommon. On the theoretical side, population genetic models suggest that, compared with the combined effects of drift and selection, epistasis generates a negligible amount of linkage disequilibria. Here, we assess these criticisms and discuss to what extent they invalidate the MDH as an explanation for the evolution of recombination.

Calculating Bootstrap Probabilities of Phylogeny Using Multilocus Sequence Data

Tae-Kun Seo — 2008-04-15T04:09:39-00:00

Mol Biol Evol, Vol. 25, No. 5. (1 May 2008), pp. 960-971.

Phylogeny estimation is extremely crucial in the study of molecular evolution. The increase in the amount of available genomic data facilitates phylogeny estimation from multilocus sequence data. Although maximum likelihood and Bayesian methods are available for phylogeny reconstruction using multilocus sequence data, these methods require heavy computation, and their application is limited to the analysis of a moderate number of genes and taxa. Distance matrix methods present suitable alternatives for analyzing huge amounts of sequence data. However, the manner in which distance methods can be applied to multilocus sequence data remains unknown. Here, we suggest new procedures to estimate molecular phylogeny using multilocus sequence data and evaluate its significance in the framework of the distance method. We found that concatenation of the multilocus sequence data may result in incorrect phylogeny estimation with an extremely high bootstrap probability (BP), which is due to incorrect estimation of the distances and intentional ignorance of the intergene variations. Therefore, we suggest that the distance matrices for multilocus sequence data be estimated separately and these matrices be subsequently combined to reconstruct phylogeny instead of phylogeny reconstruction using concatenated sequence data. To calculate the BPs of the reconstructed phylogeny, we suggest that 2-stage bootstrap procedures be adopted; in this, genes are resampled followed by resampling of the sequence columns within the resampled genes. By resampling the genes during calculation of BPs, intergene variations are properly considered. Via simulation studies and empirical data analysis, we demonstrate that our 2-stage bootstrap procedures are more suitable than the conventional bootstrap procedure that is adopted after sequence concatenation. 10.1093/molbev/msn043

Networks of genomic co-occurrence capture characteristics of human influenza A (H3N2) evolution

Xiangjun Du — 2007-11-27T17:25:40-00:00

Genome Res. (21 November 2007), gr.6969007.

The recent availability of full genomic sequence data for a large number of human influenza A (H3N2) virus isolates over many years provides us an opportunity to analyze human influenza virus evolution by considering all gene segments simultaneously. However, such analysis requires development of new computational models that can capture the complex evolutionary features over the entire genome. By analyzing nucleotide co-occurrence over the entire genome of human H3N2 viruses, we have developed a network model to describe H3N2 virus evolutionary patterns and dynamics. The network model effectively captures the evolutionary antigenic features of H3N2 virus at the whole-genome level and accurately describes the complex evolutionary patterns between individual gene segments. Our analyses show that the co-occurring nucleotide modules apparently underpin the dynamics of human H3N2 evolution and that amino acid substitutions corresponding to nucleotide co-changes cluster preferentially in known antigenic regions of the viral HA. Therefore, our study demonstrates that nucleotide co-occurrence networks represent a powerful method for tracking influenza A virus evolution and that cooperative genomic interaction is a major force underlying influenza virus evolution. 10.1101/gr.6969007