Biology subjects

Begum, T.

Publications and source records attributed to Begum, T..

4 recordsLinked to original sources

bioRxiv2023

Phylogenetic modeling provides evidence for sudden shifts in expression after small-scale duplication in vertebrates and strong support for the ortholog conjecture

Gene duplication is a potential source of innovation, but the evolutionary dynamics of functional change are still poorly understood. Under the debated "ortholog conjecture", most functional change and innovation is assumed to follow duplication. Testing the ortholog conjecture allows to better understand and characterize the way in which gene function evolves. Most models of functional evolution assume continuous change, an assumption which we challenge here. We have applied a Levy model of evolutionary trait jumps to the evolution of gene expression in vertebrates, with a special focus on duplication in teleost fishes. We show for the first time that trait jumps strongly affects paralogs, in addition to other modes of functional evolution. We find that at least 25% of teleost fish small-scale duplicates follow a rapid evolutionary rate shift model for both expression level and tissue-specificity, much more than after speciations. However, genome-wide duplicates (ohnologs) do not support such a trait jump model, and thus follow a different evolutionary dynamic. While there is some evidence for more positive selection at the protein-coding level after duplication, it is not strongly linked to jumps in expression. Finally, both small-scale paralogs and ohnologs strongly support the ortholog conjecture by contrasting speciation branches pre- and post-duplication to the duplication branches themselves, with trait jumps explaining much of the higher phylogenetic independent contrasts between small-scale paralogs. Significance statementThe debate on the ortholog conjecture, i.e. that gene function changes little between orthologs but changes frequently between paralogs, provides a framework to understand better the evolution of gene function. Here we add two pieces to the puzzle: a novel way to use phylogenetic contrasts to test the ortholog conjecture, by comparing not only duplication to speciation, but speciation according to whether they were preceded by a duplication; and a model of jumps rather than continuous change of gene function. We tested these on vertebrates, with emphasis on teleost fishes, distinguishing small-scale duplications and whole-genome duplication; in all cases we support strongly the ortholog conjecture. We find that trait jumps strongly affect small-scale paralogs but not genome duplication paralogs, providing an exciting new model for gene function evolution.

evolutionary biology↗

bioRxiv2020

Performance of a phylogenetic independent contrast method and an improved pairwise comparison under different scenarios of trait evolution after speciation and duplication

O_LIDespite the importance of gene function to evolutionary biology, the applicability of comparative methods to gene function is poorly known. A specific case which has crystalized methodological questions is the "ortholog conjecture", the hypothesis that function evolves faster after duplication (i.e., in paralogs), and conversely is conserved between orthologs. Since the mode of functional evolution after duplication is not well known, we investigate under which reasonable evolutionary scenarios phylogenetic independent contrasts or pairwise comparisons can recover a putative signal of different functional evolution between orthologs and paralogs. C_LIO_LIWe investigate three different simulation models, which represent reasonable but simplified hypotheses about the evolution of a gene function trait. These are time dependent trait acceleration, correlated changes in rates of both sequence and trait evolution, and asymmetric trait jump. For each model we tested phylogenetic independent contrasts and an improved pairwise comparison method which accounts for interactions between events and node age. C_LIO_LIBoth approaches lose power to detect the trend of functional evolution when the functional trait accelerates for a long time following duplication for trees with many duplications, with better power of phylogenetic contrasts under intermediate scenarios. Concomitant increase in evolutionary rates of sequence and of trait after duplication can lead to both an incorrect rejection of the null under null simulations of trait evolution, and a false rejection of the ortholog conjecture under ortholog conjecture simulations, by phylogenetic independent contrasts. Improved pairwise comparisons are robust to this bias. Both approaches perform equally well under rapid shifts in traits. C_LIO_LIConsidering our ignorance of gene function evolution, and the potential for bias under simple models, we recommend methodological pluralism in studying gene family evolution. Functional phylogenomics is complex and results supported by only one method should be treated with caution. C_LI

evolutionary biology↗

bioRxiv2019

Phylogenetic comparative methods are problematic when applied to gene trees with speciation and duplication nodes: correcting for biases in testing the ortholog conjecture

How gene function evolves is a central question of evolutionary biology. It can be investigated by comparing functional genomics results between species and between genes. Most comparative studies of functional genomics have used pairwise comparisons. Yet it has been shown that this can provide biased results, since genes, like species, are phylogenetically related. Phylogenetic comparative methods should allow to correct for this, but they depend on strong assumptions, including unbiased tree estimates relative to the hypothesis being tested. Such methods have recently been used to test the "ortholog conjecture", the hypothesis that functional evolution is faster in paralogs than in orthologs. Whereas pairwise comparisons of tissue specificity ({tau}) provided support for the ortholog conjecture, phylogenetic independent contrasts did not. Our reanalysis on the same gene trees identified problems with the time calibration of duplication nodes. We find that the gene trees used suffer from important biases, due to the inclusion of trees with no duplication nodes, to the relative age of speciations and duplications, to systematic differences in branch lengths, and to non-Brownian motion of tissue-specificity on many trees. We find that incorrect implementation of phylogenetic method in empirical gene trees with duplications can be problematic. Controlling for biases allows to successfully use phylogenetic methods to study the evolution of gene function, and provides some support for the ortholog conjecture using three different phylogenetic approaches.

evolutionary biology↗

bioRxiv2017

The optimization of mRNA expression level by its intrinsic properties -- insights from codon usage pattern and structural stability of mRNA

The deviation from the uniform usage of synonymous codons is termed codon usage bias. A lot has been explained from the translational viewpoint for the observed phenomenon. To understand codon usage bias from the transcriptional perspective, we present here a holistic picture of this phenomenon in Saccharomyces cerevisiae, using both wild type and computationally mutated mRNAs. Although in wild type, both codon usage bias and mRNA stability positively regulate the gene (mRNA) expression level and are positively correlated with each other, any deviation from natural situation breaks such equilibrium. Computational examination of mRNA sequences with different sets of synonymous codon composition reveals that in mutated condition, the mRNA expression becomes reduced. Furthermore, constraining codon usage pattern to wild type and carrying out randomization of codons resulted in less stable mRNA. Further, we realized a Boolean Expression explaining the gene expression under various conditions of bias and mRNA stability. These studies suggest that selection of codons is favored for regulation of gene expression through potential formation of messenger RNA structures which contribute to folding stability. The naturally occurring codon composition is responsible for optimization of gene expression, and under such composition, the mRNA structure having highest stability is selected by nature.

bioinformatics↗