Dynamic Framework for Comparative and Interactive Phylogenomic Analysis of HUlnan Paralogy Blocks

Abstract

One of the major focuses of evolutionary developmental biologists is to unvei l the geneti c underpinnings of major changes in organismal design and the origin of novelties during evolutionary transitions from prokaryotes to eukaryotes, unicellular to multicellular species, metazoans to bilaterians and in vertebrates 10 vCltebrates. A vast body of evolutionary developmental studies bas revealed that differences among closely and distantly related animal taxa are associated with differences in the spatial and temporal aspects of gene expression regulation during development. Still others consider increase in gene number by duplication as a principle mechanism responsible for iJ1CreaSe in organismai complexity and diversity. OIUlo (1970) for the first time put forward the idea of two rounds of whole genome duplication events as the most plausible exp'lanation for evolutionarizi ng the vertebrate lineage (2R hypothesis). The gene constellations on several human chromosomes termed as paralogons were specul<lted <IS remnants of whole genome dupli.cations. The high quality and well~annotated sequence maps of human genome along with the constantly elevating access of genome sequence data from diverse army of animal dynasty were scrutinized to understand the historical emergence of quadruplicated regions residing on four paralogons (HSA:217112117, HSA: 1/2/8/20, HSA: 1/6/9119 and I-ISA:415/8/10). The detailed phylogenetic anaJysis was calTied out 011 193 Illultigene families, having representation of their members on at least three chromosomes of pm1icular paralogon and the results were stored in the fOll11 of PAJ-IG database. The PAHG database is a user friendly and novel model for interactive browsing and comparative analysis of human paraJogy blocks. Tlle database provides comparisons of gene families under a framework of their shared phylogenetic history. The topology comparison approach was employed to classify the members of these gene families into distinct co-duplicated groups. Availabi li ty of PAHG as a web based database with graphicaJ visualizations of embedded information encourage better comparisons of gene families inhabiting paralogy blocks. This database pwvides a platform ror bioinfonnutics researchers and evolutionary biologists to inv.estigate genome dupli cation mechanisms that shaped the present architecture of human genome.