Claire C Morgan

Imperial College London | Imperial · Division of Diabetes, Endocrinology and Metabolism

Polar bears are uniquely adapted to life in the High Arctic and have undergone drastic physiological changes in response to Arctic climates and a hyperlipid diet of primarily marine mammal prey. We analyzed 89 complete genomes of polar bear and brown bear using population genomic modeling and show that the species diverged only 479-343 thousand yea...

Placental mammals display a huge range of life history traits, including size, longevity, metabolic rate and germ line generation time. Although a number of general trends have been proposed between these traits, there are exceptions that warrant further investigation. Species such as naked mole rat, human and certain bat species all exhibit extrem...

Heterogeneity among life traits in mammals has resulted in considerable phylogenetic conflict, particularly concerning the position of the placental root. Layered upon this are gene- and lineage-specific variation in amino acid substitution rates and compositional biases. Life trait variations that may impact upon mutational rates are longevity, me...

Background Cancer, much like most human disease, is routinely studied by utilizing model organisms. Of these model organisms, mice are often dominant. However, our assumptions of functional equivalence fail to consider the opportunity for divergence conferred by ~180 Million Years (MY) of independent evolution between these species. For a given set...

Reproductive proteins are central to the continuation of all mammalian species. The evolution of these proteins has been greatly influenced by environmental pressures induced by pathogens, rival sperm, sexual selection and sexual conflict. Positive selection has been demonstrated in many of these proteins with particular focus on primate lineages....

Genetic studies promise to provide insight into the molecular mechanisms underlying type 2 diabetes (T2D). Variants associated with T2D are often located in tissue-specific enhancer clusters or super-enhancers. So far, such domains have been defined through clustering of enhancers in linear genome maps rather than in three-dimensional (3D) space. F...

Genetic studies promise to provide insight into the molecular mechanisms underlying type 2 diabetes (T2D). Variants associated with T2D are often located in tissue-specific enhancer regions (enhancer clusters, stretch enhancers or super-enhancers). So far, such domains have been defined through clustering of enhancers in linear genome maps rather t...

BACKGROUND: The adult mammalian heart has little regenerative capacity after myocardial infarction (MI), whereas neonatal mouse heart regenerates without scarring or dysfunction. However, the underlying pathways are poorly defined. We sought to derive insights into the pathways regulating neonatal development of the mouse heart and cardiac regenera...

Table S5. DM CpGs and DMRs in 7-Day Cut Sciatic Nerve and DM CpGs that Are in Close Proximity to Mapped Active Enhancers and Their Associated Genes, Related to Figures 5 and 6 (A) Co-ordinates of each significantly DM CpG with supporting p-adjusted value and DM% between uncut and cut seven-day nerves. Individual C to CT % for each DM CpG and its b...

Document S1. Supplemental Experimental Procedures, Figures S1–S5, and Tables S2 and S6

Table S1. List of Significantly Differentially Expressed RNAs and Annotated and Predicted lncRNAs 7 Days after Nerve Cut from the RNA-Seq Study, Related to Figures 1, 2, and 3 (A) All differentially expressed RNAs seven days after nerve cut from RNA-seq analysis. Differentially expressed annotated lncRNAs (B) and predicted lncRNAs (C). Average and...

Table S3. EMT-Associated Genes and miRNAs Expressed in the Injured Nerve, Related to Figures 1 and 4 List of enriched EMT genes between (A) uncut and seven day cut nerves from RNA-seq study, (B) miRNAs between uncut and three day cut nerves, (C) miRNAs between uncut and seven day cut nerves and (D) miRNAs between three and seven day cut nerves.

Table S4. List of Significantly Differentially Expressed miRNAs 3 and 7 Days after Nerve Cut from the Small RNA-Seq Study, Related to Figure 4 Differentially expressed miRNAs between (A) uncut versus three days after nerve cut, (B) uncut versus seven days after nerve cut and, (C), three days versus seven days after nerve cut. Average and condition...

Repair Schwann cells play a critical role in orchestrating nerve repair after injury, but the cellular and molecular processes that generate them are poorly understood. Here, we perform a combined whole-genome, coding and non-coding RNA and CpG methylation study following nerve injury. We show that genes involved in the epithelial-mesenchymal trans...

The reanalysis of publicly available GWAS data represents a powerful and cost-effective opportunity to gain insights into the genetics and pathophysiology of complex diseases. We demonstrate this by gathering and reanalyzing public type 2 diabetes (T2D) GWAS data for 70,127 subjects, using an innovative imputation and association strategy based on...

There are numerous phylogenetic reconstruction methods and models available—but which should you use and why? Important considerations in phylogenetic analyses include data quality, structure, signal, alignment length and sampling. If poorly modelled, variation in rates of change across proteins and across lineages can lead to incorrect phylogeny r...

It has been proposed that positive selection may be associated with protein functional change. For example, human and macaque have different outcomes to HIV infection and it has been shown that residues under positive selection in the macaque TRIM5α receptor locate to the region known to influence species-specific response to HIV. In general, howev...

Mitochondrial data have traditionally been used in reconstructing a variety of species phylogenies. The low rates of recombination and thorough characterization of mitochondrial data across vertebrate species make it a particularly attractive phylogenetic marker. The relatively low number of fully sequenced mammal genomes and the lack of extensive...

Complete set of all multiple sequence alignments used in the analysis. The data is presented on a gene-by-gene basis in nexus format.

Full set of recombination test results on a per gene and per species basis. The value highlighted in yellow for TP53 represents a region where recombination was detected with reasonable confidence that also coincided with a positively selected residue (i.e. false positive).

Likelihood ratio tests performed and their associated significance values.

Details of the data used in the analysis, the 21 species and their genome coverage. Orthologs that were not found by the Ensembl genome browser are labeled in black, orthologs identified are shown in white.

Full set of models, associated likelihood scores and parameter estimates for all genes in the colon cancer gene dataset. This information is given alphabetically on a gene-by-gene basis. All estimated parameters, Likelihood values and BEB or NEB sites are listed.

Additional Table 1 - Results of amino acid composition bias per gene. Results of the amino acid composition bias test and shown here on a per gene basis. We would expect that if two species have similarly and significantly (P < 0.05) biased amino acid composition that they would be drawn together on the phylogeny. Those with P < 0.05 scores are hig...

Additional Table 4 - Results of root mean squared deviation (RMSD) analysis for comparing binary trees. This table summarizes the results of comparing the site stripped phylogenies with the ideal species phylogeny. In the first column is the gene name. Each of the subsequent columns represents a category of site variation that is removed (1 is the...

Additional Table 7 - Summary of data used in the analysis. Species names, unique identifiers and sequence lengths are given for all data. Summary of data used in the analysis. Species names, unique identifiers for Ensembl (ENS) or Swiss-Prot and database versions are given. The sequence length per species are given for all genes.

Additional Table 8 - Parameters for Phylogeny Reconstruction per gene. The parameters used to reconstruct each gene tree in MrBayes are shown. The model of rate heterogeneity for each gene is shown, along with the number of generations required, and the number of markov chains (these values vary based on the size of the dataset).

Additional Table 9 - Likelihood ratio tests (LRTs) performed using all evolutionary models used in selection analysis. Details on all likelihood ratio tests performed in the analysis. The models are denoted by their abbreviated names, Model A1 is denoted as Model A null throughout the manuscript. The number of degrees of freedom (df) are shown, thi...

Additional Table 2 - Results of base composition bias per gene. Results of the base composition bias test and shown here on a per gene basis. We would expect that if two species have similarly and significantly (P < 0.05) biased base composition that they would be drawn together on the phylogeny. Those with P < 0.05 scores are highlighted but are d...

Additional Table 3 - Results of likelihood mapping test for phylogenetic support and conflict estimated for each gene. Results of Likelihood mapping test are shown here on a gene-by-gene basis. This table summarizes the amount of phylogenetic signal and conflict in each alignment. The three possible topologies for each quartet of species are repres...

Additional Table 5 - Results of the SH test for site-stripped gene versus ideal species phylogeny. This table summarizes the results of comparing the site stripped phylogenies with the ideal species phylogeny using the SH test, this is a more statistically robust approach and more suited to multi-furcating topologies such as those in the dataset. E...

Additional Table 6(a-k) - Complete results of Maximum likelihood analysis for selective pressure variation per gene. For each gene analyzed (a-k) the results are shown in full on a gene-by-gene basis (in alphabetical order). The layout of each table is identical for each gene. The corresponding LRTs performed and all scores and values computed are...

Thromboxane A(2) (TxA(2)), the principle product of platelet COX-1-dependent arachidonic acid metabolism, directs multiple pro-atherogenic processes via its receptor, TP. Oxidative challenge offsets TP degradation, a key component in limiting TxA(2)'s actions. Following TP activation, we observed cellular reactive oxygen species (ROS) generation co...