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Reed A Cartwright

Publications and source records attributed to Reed A Cartwright.

4 recordsLinked to original sources

Logarithmic gap costs decrease alignment accuracy.

BACKGROUND: Studies on the distribution of indel sizes have consistently found that they obey a power law. This finding has lead several scientists to propose that logarithmic gap costs, G (k) = a + c ln k, are more biologically realistic than affine gap costs, G (k) = a + bk, for sequence alignment. Since quick and efficient affine costs are currently the most popular way to globally align sequences, the goal of this paper is to determine whether logarithmic gap costs improve alignment accuracy significantly enough the merit their use over the faster affine gap costs. RESULTS: A group of simulated sequences pairs were globally aligned using affine, logarithmic, and log-affine gap costs. Alignment accuracy was calculated by comparing resulting alignments to actual alignments of the sequence pairs. Gap costs were then compared based on average alignment accuracy. Log-affine gap costs had the best accuracy, followed closely by affine gap costs, while logarithmic gap costs performed poorly. Subsequently a model was developed to explain the results. CONCLUSION: In contrast to initial expectations, logarithmic gap costs produce poor alignments and are actually not implied by the power-law behavior of gap sizes, given typical match and mismatch costs. Furthermore, affine gap costs not only produce accurate alignments but are also good approximations to biologically realistic gap costs. This work provides added confidence for the biological relevance of existing alignment algorithms.

Algorithms↗

DNA assembly with gaps (Dawg): simulating sequence evolution.

MOTIVATION: Relationships amongst taxa are inferred from biological data using phylogenetic methods and procedures. Very few known phylogenies exist against which to test the accuracy of our inferences. Therefore, in the absence of biological data, simulated data must be used to test the accuracy of methods which produce these inferences. Researchers have limited or non-existent options for simulations useful for studying the impact of insertions, deletions, and alignments on phylogenetic accuracy. RESULTS: To satisfy this gap I have developed a new algorithm of indel formation and incorporated it into a new, flexible, and portable application for sequence simulation. The application, called Dawg, simulates phylogenetic evolution of DNA sequences in continuous time using the robust general time reversible model with gamma and invariant rate heterogeneity and a novel length-dependent model of indel formation. On completion, Dawg produces the true alignment of the simulated sequences. Unlike other applications, Dawg allows indel lengths to be explicitly distributed via a biologically realistic power law. Many options are available to allow users to customize their simulations and results. Because simulating with indels would be problematic if biologically realistic parameters could not be estimated, a script is provided with Dawg that can estimate the parameters of indel formation from sequence data. Dawg was applied to the sequences of four chloroplast trnK introns. It was used to parametrically bootstrap an estimation of the rate of indel formation for the phylogeny. Because Dawg can assist in parametric bootstrapping of sequence data it is useful beyond phylogenetics, such as studying alignment algorithms or parameters of molecular evolution. AVAILABILITY: Dawg 1.0.0 can be obtained at the following websites: http://www.genetics.uga.edu/sw/ or http://scit.us/dawg/. The package includes source code, example files, a brief manual and helper scripts. Binary distributions are available for Windows and Macintosh OS X. A development page for Dawg exists at http://scit.us/dawg/, with links to a Subversion repository, mailing lists and updated versions.

Base Sequence↗

Frequency-dependent selection with dominance: a window onto the behavior of the mean fitness.

Selection in which fitnesses vary with the changing genetic composition of the population may facilitate the maintenance of genetic diversity in a wide range of organisms. Here, a detailed theoretical investigation is made of a frequency-dependent selection model, in which fitnesses are based on pairwise interactions between the two phenotypes at a diploid, diallelic, autosomal locus with complete dominance. The allele frequency dynamics are fully delimited analytically, along with all possible shapes of the mean fitness function in terms of where it increases or decreases as a function of the current allele frequency in the population. These results in turn allow possibly the first complete characterization of the dynamical behavior by the mean fitness through time under frequency-dependent selection. Here the mean fitness (i) monotonically increases, (ii) monotonically decreases, (iii) initially increases and then decreases, or (iv) initially decreases and then increases as equilibrium is approached. We analytically derive the exact initial and fitness conditions that produce each dynamic and how often each arises. Computer simulations with random initial conditions and fitnesses reveal that the potential decline in mean fitness is not negligible; on average a net decrease occurs 20% of the time and reduces the mean fitness by >17%.

Alleles↗