Conservation anchors in the vertebrate genome.
Ontology highlight
ABSTRACT:
SUBMITTER: Aloni R
PROVIDER: S-EPMC1175977 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:This article describes a set of alignments of 28 vertebrate genome sequences that is provided by the UCSC Genome Browser. The alignments can be viewed on the Human Genome Browser (March 2006 assembly) at http://genome.ucsc.edu, downloaded in bulk by anonymous FTP from http://hgdownload.cse.ucsc.edu/goldenPath/hg18/multiz28way, or analyzed with the Galaxy server at http://g2.bx.psu.edu. This article illustrates the power of this resource for exploring vertebrate and mammalian evolution, using three examples. First, we present several vignettes involving insertions and deletions within protein-coding regions, including a look at some human-specific indels. Then we study the extent to which start codons and stop codons in the human sequence are conserved in other species, showing that start codons are in general more poorly conserved than stop codons. Finally, an investigation of the phylogenetic depth of conservation for several classes of functional elements in the human genome reveals striking differences in the rates and modes of decay in alignability. Each functional class has a distinctive period of stringent constraint, followed by decays that allow (for the case of regulatory regions) or reject (for coding regions and ultraconserved elements) insertions and deletions.
| S-EPMC2099589 | biostudies-literature
Project description:Vertebrates share the same general body plan and organs, possess related sets of genes, and rely on similar physiological mechanisms, yet show great diversity in morphology, habitat and behavior. Alteration of gene regulation is thought to be a major mechanism in phenotypic variation and evolution, but relatively little is known about the broad patterns of conservation in gene expression in non-mammalian vertebrates.We measured expression of all known and predicted genes across twenty tissues in chicken, frog and pufferfish. By combining the results with human and mouse data and considering only ten common tissues, we have found evidence of conserved expression for more than a third of unique orthologous genes. We find that, on average, transcription factor gene expression is neither more nor less conserved than that of other genes. Strikingly, conservation of expression correlates poorly with the amount of conserved nonexonic sequence, even using a sequence alignment technique that accounts for non-collinearity in conserved elements. Many genes show conserved human/fish expression despite having almost no nonexonic conserved primary sequence.There are clearly strong evolutionary constraints on tissue-specific gene expression. A major challenge will be to understand the precise mechanisms by which many gene expression patterns remain similar despite extensive cis-regulatory restructuring.
| S-EPMC2689434 | biostudies-literature
Project description:BACKGROUND: The myocyte enhancer factor 2 (MEF2) gene family is broadly expressed during the development and maintenance of muscle cells. Although a great deal has been elucidated concerning MEF2 transcription factors' regulation of specific gene expression in diverse programs and adaptive responses, little is known about the origin and evolution of the four members of the MEF2 gene family in vertebrates. METHODOLOGY/PRINCIPAL FINDINGS: By phylogenetic analyses, we investigated the origin, conservation, and evolution of the four MEF2 genes. First, among the four MEF2 paralogous branches, MEF2B is clearly distant from the other three branches in vertebrates, mainly because it lacks the HJURP_C (Holliday junction recognition protein C-terminal) region. Second, three duplication events might have occurred to produce the four MEF2 paralogous genes and the latest duplication event occurred near the origin of vertebrates producing MEF2A and MEF2C. Third, the ratio (K(a)/K(s)) of non-synonymous to synonymous nucleotide substitution rates showed that MEF2B evolves faster than the other three MEF2 proteins despite purifying selection on all of the four MEF2 branches. Moreover, a pair model of M0 versus M3 showed that variable selection exists among MEF2 proteins, and branch-site analysis presented that sites 53 and 64 along the MEF2B branch are under positive selection. Finally, and interestingly, substitution rates showed that type II MADS genes (i.e., MEF2-like genes) evolve as slowly as type I MADS genes (i.e., SRF-like genes) in animals, which is inconsistent with the fact that type II MADS genes evolve much slower than type I MADS genes in plants. CONCLUSION: Our findings shed light on the relationship of MEF2A, B, C, and D with functional conservation and evolution in vertebrates. This study provides a rationale for future experimental design to investigate distinct but overlapping regulatory roles of the four MEF2 genes in various tissues.
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Project description:Identifying priority areas for biodiversity is essential for directing conservation resources. Fundamentally, we must know where individual species live, which ones are vulnerable, where human actions threaten them, and their levels of protection. As conservation knowledge and threats change, we must reevaluate priorities. We mapped priority areas for vertebrates using newly updated data on >21,000 species of mammals, amphibians, and birds. For each taxon, we identified centers of richness for all species, small-ranged species, and threatened species listed with the International Union for the Conservation of Nature. Importantly, all analyses were at a spatial grain of 10 × 10 km, 100 times finer than previous assessments. This fine scale is a significant methodological improvement, because it brings mapping to scales comparable with regional decisions on where to place protected areas. We also mapped recent species discoveries, because they suggest where as-yet-unknown species might be living. To assess the protection of the priority areas, we calculated the percentage of priority areas within protected areas using the latest data from the World Database of Protected Areas, providing a snapshot of how well the planet's protected area system encompasses vertebrate biodiversity. Although the priority areas do have more protection than the global average, the level of protection still is insufficient given the importance of these areas for preventing vertebrate extinctions. We also found substantial differences between our identified vertebrate priorities and the leading map of global conservation priorities, the biodiversity hotspots. Our findings suggest a need to reassess the global allocation of conservation resources to reflect today's improved knowledge of biodiversity and conservation.
| S-EPMC3710798 | biostudies-literature
Project description:BackgroundA number of vertebrate highly conserved elements (HCEs) have been detected and their genomic interval distances have been reported to be more conserved than protein coding genes among mammalian genomes. A characteristic of the human - non-mammalian comparisons is a bimodal distribution of relative distance difference of conserved consecutive HCE pairs; and it is difficult to attribute such profile to a random assortment. We therefore undertook an analysis of the human genomic regions confined by consecutive HCE pairs common to eight genomes (human, mouse, rat, chicken, frog, zebrafish, tetradon and fugu).ResultsAmong HCE pairs, we found that some consistently preserve highly conserved interval distance among genomes while others have relatively low distance conservation. Using a partition method, we detected two groups of inter-HCE regions (IHRs) with distinct distance conservation pattern in vertebrate genomes: IHR1s that are bordered by HCE pairs with relative small distance variation, and IHR2s with larger distance difference values. Compared to random background, annotated repeat sequences are significantly less frequent in IHR1s than IHR2s, which reflects a correlation between repeat sequences and the length expansion of IHRs. Both groups of IHRs are unexpectedly enriched in human indel (i.e. insertion and deletion) polymorphism-variations than random background. The correlation between the percentage of conserved sequence and human IHR length was stronger for IHR1 than IHR2. Both groups of IHRs are significantly enriched for CpG islands.ConclusionThe data suggest that subsets of HCE pairs may undergo different evolutionary paths in light of their genomic distance conservation, and that sets of genomic regions pertain to HCEs, as well as the region in which HCEs reside, should be treated as integrated domains.
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Project description:Salmon and other anadromous fish are consumed by vertebrates with distinct life history strategies to capitalize on this ephemeral pulse of resource availability. Depending on the timing of salmon arrival, this resource may be in surplus to the needs of vertebrate consumers if, for instance, their populations are limited by food availability during other times of year. However, the life history of some consumers enables more efficient exploitation of these ephemeral resources. Bears can deposit fat and then hibernate to avoid winter food scarcity, and highly mobile consumers such as eagles, gulls, and other birds can migrate to access asynchronous pulses of salmon availability. We used camera traps on pink, chum, and sockeye salmon spawning grounds with various run times and stream morphologies, and on individual salmon carcasses, to discern potentially different use patterns among consumers. Wildlife use of salmon was highly heterogeneous. Ravens were the only avian consumer that fed heavily on pink salmon in small streams. Eagles and gulls did not feed on early pink salmon runs in streams, and only moderately at early sockeye runs, but were the dominant consumers at late chum salmon runs, particularly on expansive river flats. Brown bears used all salmon resources far more than other terrestrial vertebrates. Notably, black bears were not observed on salmon spawning grounds despite being the most frequently observed vertebrate on roads and trails. From a conservation and management perspective, all salmon species and stream morphologies are used extensively by bears, but salmon spawning late in the year are disproportionately important to eagles and other highly mobile species that are seasonally limited by winter food availability.
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Project description:Heart disease is the leading cause of death in the western world. Attaining a mechanistic understanding of human heart development and homeostasis and the molecular basis of associated disease states relies on the use of animal models. Here, we present the cardiac proteomes of 4 model vertebrates with dual circulatory systems: the pig (Sus scrofa), the mouse (Mus musculus), and 2 frogs (Xenopus laevis and Xenopus tropicalis). Determination of which proteins and protein pathways are conserved and which have diverged within these species will aid in our ability to choose the appropriate models for determining protein function and to model human disease. We uncover mammalian- and amphibian-specific, as well as species-specific, enriched proteins and protein pathways. Among these, we find and validate an enrichment in cell-cycle-associated proteins within Xenopus laevis. To further investigate functional units within cardiac proteomes, we develop a computational approach to profile the abundance of protein complexes across species. Finally, we demonstrate the utility of these data sets for predicting appropriate model systems for studying given cardiac conditions by testing the role of Kielin/chordin-like protein (Kcp), a protein found as enriched in frog hearts compared to mammals. We establish that germ-line mutations in Kcp in Xenopus lead to valve defects and, ultimately, cardiac failure and death. Thus, integrating these findings with data on proteins responsible for cardiac disease should lead to the development of refined, species-specific models for protein function and disease states.
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Project description:Human-driven extinction threatens entire lineages across the Tree of Life. Here we assess the conservation status of jawed vertebrate evolutionary history, using three policy-relevant approaches. First, we calculate an index of threat to overall evolutionary history, showing that we expect to lose 86-150 billion years (11-19%) of jawed vertebrate evolutionary history over the next 50-500 years. Second, we rank jawed vertebrate species by their EDGE scores to identify the highest priorities for species-focused conservation of evolutionary history, finding that chondrichthyans, ray-finned fish and testudines rank highest of all jawed vertebrates. Third, we assess the conservation status of jawed vertebrate families. We found that species within monotypic families are more likely to be threatened and more likely to be in decline than other species. We provide a baseline for the status of families at risk of extinction to catalyse conservation action. This work continues a trend of highlighting neglected groups-such as testudines, crocodylians, amphibians and chondrichthyans-as conservation priorities from a phylogenetic perspective.
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Project description:The evolutionary origin of vertebrates included innovations in sensory processing associated with the acquisition of a predatory lifestyle1. Vertebrates perceive external stimuli through sensory systems serviced by cranial sensory ganglia, whose neurons arise predominantly from cranial placodes; however, the understanding of the evolutionary origin of placodes and cranial sensory ganglia is hampered by the anatomical differences between living lineages and the difficulty in assigning homology between cell types and structures. Here we show that the homeobox transcription factor Hmx is a constitutive component of vertebrate sensory ganglion development and that in the tunicate Ciona intestinalis, Hmx is necessary and sufficient to drive the differentiation programme of bipolar tail neurons, cells previously thought to be homologues of neural crest2,3. Using Ciona and lamprey transgenesis, we demonstrate that a unique, tandemly duplicated enhancer pair regulated Hmx expression in the stem-vertebrate lineage. We also show notably robust vertebrate Hmx enhancer function in Ciona, demonstrating that deep conservation of the upstream regulatory network spans the evolutionary origin of vertebrates. These experiments demonstrate regulatory and functional conservation between Ciona and vertebrate Hmx, and point to bipolar tail neurons as homologues of cranial sensory ganglia.
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Project description:Caspases are proteases conserved throughout Metazoans and responsible for initiating and executing the apoptotic program. Currently, there are over 1800 known apoptotic caspase substrates, many of them known regulators of cell proliferation and death, which makes them attractive therapeutic targets. However, most caspase substrates are by-standers, and identifying novel apoptotic mediators amongst all caspase substrates remains an unmet need. Here, we conducted an in silico search for significant apoptotic caspase targets across different species within the Vertebrata subphylum, using different criteria of conservation combined with structural features of cleavage sites. We observed that P1 aspartate is highly conserved while the cleavage sites are extensively variable and found that cleavage sites are located primarily in coiled regions composed of hydrophilic amino acids. Using the combination of these criteria, we determined the final list of the 107 most relevant caspase substrates including 30 novel targets previously unknown for their role in apoptosis and cancer. These newly identified substrates can be potential regulators of apoptosis and candidates for anti-tumor therapy.
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