Biomedical subjects

Shruti Rastogi

Publications and source records attributed to Shruti Rastogi.

3 recordsLinked to original sources

PubMed2007

Evolution after gene duplication: models, mechanisms, sequences, systems, and organisms.

Gene duplication is postulated to have played a major role in the evolution of biological novelty. Here, gene duplication is examined across levels of biological organization in an attempt to create a unified picture of the mechanistic process by which gene duplication can have played a role in generating biodiversity. Neofunctionalization and subfunctionalization have been proposed as important processes driving the retention of duplicate genes. These models have foundations in population genetic theory, which is now being refined by explicit consideration of the structural constraints placed upon genes encoding proteins through physical chemistry. Further, such models can be examined in the context of comparative genomics, where an integration of gene-level evolution and species-level evolution allows an assessment of the frequency of duplication and the fate of duplicate genes. This process, of course, is dependent upon the biochemical role that duplicated genes play in biological systems, which is in turn dependent upon the mechanism of duplication: whole genome duplication involving a co-duplication of interacting partners vs. single gene duplication. Lastly, the role that these processes may have played in driving speciation is examined.

Animals↗

PubMed2006

Evaluation of models for the evolution of protein sequences and functions under structural constraint.

In the field of evolutionary structural genomics, methods are needed to evaluate why genomes evolved to contain the fold distributions that are observed. In order to study the effects of population dynamics in the evolved genomes we need fast and accurate evolutionary models which can analyze the effects of selection, drift and fixation of a protein sequence in a population that are grounded by physical parameters governing the folding and binding properties of the sequence. In this study, various knowledge-based, force field, and statistical methods for protein folding have been evaluated with four different folds: SH2 domains, SH3 domains, Globin-like, and Flavodoxin-like, to evaluate the speed and accuracy of the energy functions. Similarly, knowledge-based and force field methods have been used to predict ligand binding specificity in SH2 domain. To demonstrate the applicability of these methods, the dynamics of evolution of new binding capabilities by an SH2 domain is demonstrated.

Computational Biology↗

PubMed2005

Subfunctionalization of duplicated genes as a transition state to neofunctionalization.

BACKGROUND: Gene duplication has been suggested to be an important process in the generation of evolutionary novelty. Neofunctionalization, as an adaptive process where one copy mutates into a function that was not present in the pre-duplication gene, is one mechanism that can lead to the retention of both copies. More recently, subfunctionalization, as a neutral process where the two copies partition the ancestral function, has been proposed as an alternative mechanism driving duplicate gene retention in organisms with small effective population sizes. The relative importance of these two processes is unclear. RESULTS: A set of lattice model genes that fold and bind to two peptide ligands with overlapping binding pockets, but not a third ligand present in the cell was designed. Each gene was duplicated in a model haploid species with a small constant population size and no recombination. One set of models allowed subfunctionalization of binding events following duplication, while another set did not allow subfunctionalization. Modeling under such conditions suggests that subfunctionalization plays an important role, but as a transition state to neofunctionalization rather than as a terminal fate of duplicated genes. There is no apparent selective pressure to maintain redundancy. CONCLUSION: Subfunctionalization results in an increase in the preservation of duplicated gene copies, including those that are neofunctionalized, but never represents a substantial fraction of duplicate gene copies at any evolutionary time point and ultimately leads to neofunctionalization of those preserved copies. This conclusion also may reflect changes in gene function after duplication with time in real genomes.

Animals↗