Variation in DNA Substitution Rates among Lineages Erroneously Inferred from Simulated Clock-Like Data

BACKGROUND: The observation of variation in substitution rates among lineages has led to (1) a general rejection of the molecular clock model, and (2) the suggestion that a number of biological characteristics of organisms can cause rate variation. Accurate estimates of rate variation, and thus accurate inferences regarding the causes of rate variation, depend on accurate estimates of substitution rates. However, theory suggests that even when the substitution process is clock-like, variable numbers of substitutions can occur among lineages because the substitution process is stochastic. Furthermore, substitution rates along lineages can be misestimated, particularly when multiple substitutions occur at some sites. Although these potential causes of error in rate estimation are well understood in theory, such error has not been examined in detail; consequently, empirical studies that estimate rate variation among lineages have been unable to determine whether their results could be impacted by estimation error. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the extent to which error in rate estimation could erroneously suggest rate variation among lineages, we examined rate variation estimated for datasets simulated under a molecular clock on trees with equal and variable branch lengths. Thus, any apparent rate variation in these datasets reflects error in rate estimation rather than true differences in the underlying substitution process. We observed substantial rate variation among lineages in our simulations; however, we did not observe rate variation when average substitution rates were compared between different clades. CONCLUSIONS/SIGNIFICANCE: Our results confirm previous theoretical work suggesting that observations of among lineage rate variation in empirical data may be due to the stochastic substitution process and error in the estimation of substitution rates, rather than true differences in the underlying substitution process among lineages. However, conclusions regarding rate variation drawn from rates averaged across multiple branches are likely due to real, systematic variation in rates between groups

Spatio-temporal regulation of Wnt and retinoic acid signaling by tbx16/spadetail during zebrafish mesoderm differentiation

<p>Abstract</p> <p>Background</p> <p>A complex network of signaling pathways and transcription factors regulates vertebrate mesoderm development. Zebrafish mutants provide a powerful tool for examining the roles of individual genes in such a network. <it>spadetail (spt) </it>is a mutant with a lesion in <it>tbx16</it>, a T-box transcription factor involved in mesoderm development; the mutant phenotype includes disrupted primitive red blood cell formation as well as disrupted somitogenesis. Despite much recent progress, the downstream targets of <it>tbx16 </it>remain incompletely understood. The current study was carried out to test whether any of the five major signaling pathways are regulated by <it>tbx16 </it>during two specific stages of mesoderm development: primitive red blood cell formation in the intermediate mesoderm and somite formation in the tail paraxial mesoderm. This test was performed using Gene Set Enrichment Analysis, which identifies coordinated changes in expression among <it>a priori </it>sets of genes associated with biological features or processes.</p> <p>Results</p> <p>Our Gene Set Enrichment Analysis results identify Wnt and retinoic acid signaling as likely downstream targets of <it>tbx16 </it>in the developing zebrafish intermediate mesoderm, the site of primitive red blood cell formation. In addition, such results identify retinoic acid signaling as a downstream target of <it>tbx16 </it>in the developing zebrafish posterior somites. Finally, using candidate gene identification and <it>in situ </it>hybridization, we provide expression domain information for 25 additional genes downstream of <it>tbx16 </it>that are outside of both pathways; 23 were previously unknown downstream targets of <it>tbx16</it>, and seven had previously uncharacterized expression in zebrafish.</p> <p>Conclusions</p> <p>Our results suggest that (1) <it>tbx16 </it>regulates Wnt signaling in the developing zebrafish intermediate mesoderm, the site of primitive red blood cell formation, and (2) <it>tbx16 </it>regulates retinoic acid signaling at two distinct embryonic locations and developmental stages, which may imply ongoing spatio-temporal regulation throughout mesoderm development.</p

Phylogenomics Reveals Ancient Gene Tree Discordance in the Amphibian Tree of Life

Molecular phylogenies have yielded strong support for many parts of the amphibian Tree of Life, but poor support for the resolution of deeper nodes, including relationships among families and orders. To clarify these relationships, we provide a phylogenomic perspective on amphibian relationships by developing a taxon-specific Anchored Hybrid Enrichment protocol targeting hundreds of conserved exons which are effective across the class. After obtaining data from 220 loci for 286 species (representing 94% of the families and 44% of the genera), we estimate a phylogeny for extant amphibians and identify gene tree–species tree conflict across the deepest branches of the amphibian phylogeny. We perform locus-by-locus genealogical interrogation of alternative topological hypotheses for amphibian monophyly, focusing on interordinal relationships. We find that phylogenetic signal deep in the amphibian phylogeny varies greatly across loci in a manner that is consistent with incomplete lineage sorting in the ancestral lineage of extant amphibians. Our results overwhelmingly support amphibian monophyly and a sister relationship between frogs and salamanders, consistent with the Batrachia hypothesis. Species tree analyses converge on a small set of topological hypotheses for the relationships among extant amphibian families. These results clarify several contentious portions of the amphibian Tree of Life, which in conjunction with a set of vetted fossil calibrations, support a surprisingly younger timescale for crown and ordinal amphibian diversification than previously reported. More broadly, our study provides insight into the sources, magnitudes, and heterogeneity of support across loci in phylogenomic data sets

LTR Retrotransposons Contribute to Genomic Gigantism in Plethodontid Salamanders

Among vertebrates, most of the largest genomes are found within the salamanders, a clade of amphibians that includes 613 species. Salamander genome sizes range from ∼14 to ∼120 Gb. Because genome size is correlated with nucleus and cell sizes, as well as other traits, morphological evolution in salamanders has been profoundly affected by genomic gigantism. However, the molecular mechanisms driving genomic expansion in this clade remain largely unknown. Here, we present the first comparative analysis of transposable element (TE) content in salamanders. Using high-throughput sequencing, we generated genomic shotgun data for six species from the Plethodontidae, the largest family of salamanders. We then developed a pipeline to mine TE sequences from shotgun data in taxa with limited genomic resources, such as salamanders. Our summaries of overall TE abundance and diversity for each species demonstrate that TEs make up a substantial portion of salamander genomes, and that all of the major known types of TEs are represented in salamanders. The most abundant TE superfamilies found in the genomes of our six focal species are similar, despite substantial variation in genome size. However, our results demonstrate a major difference between salamanders and other vertebrates: salamander genomes contain much larger amounts of long terminal repeat (LTR) retrotransposons, primarily Ty3/gypsy elements. Thus, the extreme increase in genome size that occurred in salamanders was likely accompanied by a shift in TE landscape. These results suggest that increased proliferation of LTR retrotransposons was a major molecular mechanism contributing to genomic expansion in salamanders

The calcium channel β2 (CACNB2) subunit repertoire in teleosts

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