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The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete(More)
BACKGROUND We compared two methods of rooting a phylogenetic tree: the stationary and the nonstationary substitution processes. These methods do not require an outgroup. METHODS Given a multiple alignment and an unrooted tree, the maximum likelihood estimates of branch lengths and substitution parameters for each associated rooted tree are found; rooted(More)
The amount of noncoding genomic DNA sequence that aligns between human and mouse varies substantially in different regions of their genomes, and the amount of repetitive DNA also varies. In this report, we show that divergence in noncoding nonrepetitive DNA is strongly correlated with the amount of repetitive DNA in a region. We investigated aligned DNA in(More)
The genetic distance between biological sequences is a fundamental quantity in molecular evolution. It pertains to questions of rates of evolution, existence of a molecular clock, and phylogenetic inference. Under the class of continuous-time substitution models, the distance is commonly defined as the expected number of substitutions at any site in the(More)
Analysis of natural selection is key to understanding many core biological processes, including the emergence of competition, cooperation, and complexity, and has important applications in the targeted development of vaccines. Selection is hard to observe directly but can be inferred from molecular sequence variation. For protein-coding nucleotide(More)
Major histocompatibility complex class I molecules present peptides of 8-10 residues to CD8+ T cells. We used 19 predicted proteomes to determine the influence of CD8+ T cell immune surveillance on protein evolution in humans and microbial pathogens by predicting immunopeptidomes, i.e., sets of class I binding peptides present in proteomes. We find that(More)
BACKGROUND Neighboring nucleotides exert a striking influence on mutation, with the hypermutability of CpG dinucleotides in many genomes being an exemplar. Among the approaches employed to measure the relative importance of sequence neighbors on molecular evolution have been continuous-time Markov process models for substitutions that treat sequences as a(More)
BACKGROUND The nucleotide substitution rate matrix is a key parameter of molecular evolution. Several methods for inferring this parameter have been proposed, with different mathematical bases. These methods include counting sequence differences and taking the log of the resulting probability matrices, methods based on Markov triples, and maximum likelihood(More)
BACKGROUND Continuous-time Markov models allow flexible, parametrically succinct descriptions of sequence divergence. Non-reversible forms of these models are more biologically realistic but are challenging to develop. The instantaneous rate matrices defined for these models are typically transformed into substitution probability matrices using a matrix(More)
Continuous-time Markov processes are often used to model the complex natural phenomenon of sequence evolution. To make the process of sequence evolution tractable, simplifying assumptions are often made about the sequence properties and the underlying process. The validity of one such assumption, time-homogeneity, has never been explored. Violations of this(More)