Comparative analysis of DNA and amino acid sequences is now routinely employed in tracing the origins, patterns, and evolutionary relationships of homologous sequences. Due to recent advances in DNA sequencing technologies, these datasets now contain increasingly larger numbers of sequences that comprise a family of orthologous (arisen by speciation) and/or paralogous (arisen by gene duplications) sequences from diverse species. Therefore, the need for biologist-centric tools for evolutionary and functional genomics analysis of these data is growing. We propose to address these needs by expanding the scope of Molecular Evolutionary Genetics Analysis (MEGA) software to the analysis of gene families. This would involve development of new software for streamlining large gene family data acquisition, making MEGA cross-platform, and implementing efficient heuristics for estimating very large trees quickly and inferring gene duplication events and divergence times. Because sequence lengths in gene family alignments are biologically constrained, unlike species history analysis for which full genomes and multiple genes are often available to improve precision, we plan to evaluate the accuracies of phylogenetic trees produced by these extremely fast, but highly heuristic, algorithms for phylogenetic inference by means of computer simulation involving biologically realistic parameters. Insights gained from these efforts will be introduced in algorithm designs in MEGA. Overall, the software and research developments will contribute to advances in molecular evolution, bioinformatics, functional genomics, computational biology, and basic biomedicine. As always, MEGA and its source code will be made available free of charge for all uses, including research, education, and training.
Evolutionary Bioinformatics is a powerful tool for conducting in silico functional analysis of DNA and protein sequences from genes and genomes of diverse organisms. The proposed software development and fundamental research will lead to an advanced Molecular Evolutionary Genetics Analysis (MEGA) tool for use by biologists in their quest to beter understand the evolutionary dynamics of gene families residing in the genomes of humans as well as their evolutionary relatives and pathogens.
|Karim, Sajjad; NourEldin, Hend Fakhri; Abusamra, Heba et al. (2016) e-GRASP: an integrated evolutionary and GRASP resource for exploring disease associations. BMC Genomics 17:770|
|Liu, Li; Tamura, Koichiro; Sanderford, Maxwell et al. (2016) A Molecular Evolutionary Reference for the Human Variome. Mol Biol Evol 33:245-54|
|Miura, Sayaka; Tate, Stephanie; Kumar, Sudhir (2015) Using Disease-Associated Coding Sequence Variation to Investigate Functional Compensation by Human Paralogous Proteins. Evol Bioinform Online 11:245-51|
|Kumar, Avishek; Butler, Brandon M; Kumar, Sudhir et al. (2015) Integration of structural dynamics and molecular evolution via protein interaction networks: a new era in genomic medicine. Curr Opin Struct Biol 35:135-42|
|Butler, Brandon M; Gerek, Z Nevin; Kumar, Sudhir et al. (2015) Conformational dynamics of nonsynonymous variants at protein interfaces reveals disease association. Proteins 83:428-35|
|Filipski, Alan; Tamura, Koichiro; Billing-Ross, Paul et al. (2015) Phylogenetic placement of metagenomic reads using the minimum evolution principle. BMC Genomics 16 Suppl 1:S13|
|Gerek, Nevin Z; Liu, Li; Gerold, Kristyn et al. (2015) Evolutionary Diagnosis of non-synonymous variants involved in differential drug response. BMC Med Genomics 8 Suppl 1:S6|
|Battistuzzi, Fabia U; Billing-Ross, Paul; Murillo, Oscar et al. (2015) A Protocol for Diagnosing the Effect of Calibration Priors on Posterior Time Estimates: A Case Study for the Cambrian Explosion of Animal Phyla. Mol Biol Evol 32:1907-12|
|Hedges, S Blair; Marin, Julie; Suleski, Michael et al. (2015) Tree of life reveals clock-like speciation and diversification. Mol Biol Evol 32:835-45|
|Kumar, Sudhir; Liu, Li (2014) No positive selection for G allele in a p53 response element in Europeans. Cell 157:1497-9|
Showing the most recent 10 out of 47 publications