Biology subjects

Jalan, S.

Publications and source records attributed to Jalan, S..

5 recordsLinked to original sources

bioRxiv2023

Higher-order co-mutation interactions in mitochondrial genomes

Pair-wise co-mutation networks of the mitochondrial genome have already provided ample evidences about the roles of genetic interactions in the manifestation of phenotype under altered environmental conditions. Here, we present a method to construct and analyze higher-order interactions, namely, 3-uniform hypergraphs of the mitochondrial genome for different altitude populations to decipher the role of co-mutating variable sites beyond pair-wise interactions. While the weights distribution of such gene hyperedges manifested power-law for all the altitudes, we identified altitude-specific genes based on gene hyperedge weight. This framework of hypergraphs serves a promising avenue for future investigation of nuclear genomes in context of phenotypic association and genetic disorders.

systems biology↗

bioRxiv2021

Role of mitochondrial genetic interactions in determining adaptation to high altitude in human population around the globe

Physiological and haplogroup studies performed to understand high-altitude adaptation in humans are limited to individual genes and polymorphic sites. Due to stochastic evolutionary forces, the frequency of a polymorphism is affected by changes in the frequency of a near-by polymorphism on the same DNA sample making them connected in terms of evolution. Here, first we provide a method to model these mitochondrial polymorphisms as "co-mutation networks" for three high-altitude populations, Tibetan, Ethiopian and Andean. Then, by transforming these co-mutation networks into weighted and undirected gene-gene interaction (GGI) networks, we were able to identify functionally enriched genetic interactions of CYB and CO3 genes in Tibetan and Andean populations, while NADH dehydrogenase genes in Ethiopian population playing a significant role in high altitude adaptation. These co-mutation based genetic networks provide insights into the role of different set of genes in high-altitude adaptation human sub-populations.

bioinformatics↗

bioRxiv2019

Altitude-wise analysis of co-occurrence networks of mitochondrial genome in Asian population

Networks have been established as an extremely powerful framework to understand and predict the behavior of many large-scale complex systems. We have studied network motifs, the basic structural elements of networks, to describe the possible role of co-occurrence of genomic variations behind high altitude adaptation in the Asian human population. Mitochondrial DNA (mt-DNA) variations have been acclaimed as one of the key players in understanding the biological mechanisms behind adaptation to extreme conditions. To explore the cumulative effects and variations in the mitochondrial genome with the variation in the altitude, we investigated human mt-DNA sequences from the NCBI database at different altitudes under the co-occurrence motifs framework. Analysis of the co-occurrence motifs using similarity clusteringrevealed a clear distinction between lower and higher altitude regions. In addition, the previously known high altitude markers 3394 and 7697 (which are definitive sites of haplogroup M9a1a1c1b) were found to co-occur within their own gene complexes indicating the impact of intra-genic constraint on co-evolution of nucleotides. Furthermore, an ancestral RSRS50 variant 10398 was found to co-occur only at higher altitudes supporting the fact that a separate route of colonization at these altitudes might have taken place. Overall, our analysis revealed the presence of co-occurrence interactions specific to high altitude at a whole mitochondrial genome level. This study, combined with the classical haplogroups analysis is useful in understanding the role of co-occurrence of mitochondrial variations in high altitude adaptation.

systems biology↗

bioRxiv2018

Impact of mitochondrial epistatic interactions on evolution of different human subpopulations

Investigation of human mitochondrial (mt) genome variation has been shown to provide insights to the human history and natural selection. By analyzing 24,167 human mt-genome samples, collected for five continents, we have developed a co-mutation network model to investigate characteristic human evolutionary patterns. The analysis highlighted richer co-mutating regions of the mt-genome, suggesting the presence of epistasis. Specifically, a large portion of COX genes was found to co-mutate in Asian and American populations, whereas, in African, European, and Oceanic populations, there was greater co-mutation bias in hypervariable regions. Interestingly, this study demonstrated hierarchical modularity as a crucial agent for these co-mutation networks. More profoundly, our ancestry-based co-mutation module analyses showed that mutations cluster preferentially in known mitochondrial haplogroups. Contemporary human mt-genome nucleotides most closely resembled the ancestral state, and very few of them were found to be ancestral-variants. Overall, these results demonstrated that subpopulation-based biases may favor mitochondrial gene specific epistasis.

synthetic biology↗

bioRxiv2016

Codon based co-occurrence network motifs in human mitochondria

Human mitochondrial DNA (mtDNA) generates a highly divergent pool of alleles even within species that have dispersed and expanded in size. On top of that codon position bias plays a relative role in prompting population wide sequence based variations. Codon positions are immensely studied as independent evolutionary genetic markers, however co-evolution of codon positions are still largely unexplored. Using 18,411 genome samples, we analyze nucleotide co-occurrences over mitochondrial DNA of human sub-populations covering most of the mtDNA diversity on the earth. Our codon based network motif investigation reveals that codon position is one of the critical factor to form higher order motifs. It is interesting to report a different evolution of Asian genomes than those of the rest which is divulged by motifs in non-coding regions. Most notably, we demonstrate that there are preferences of codon position co-evolution with respect to codon position sensitivity implying the selective role of evolutionary processes on fundamental formation of genetic code in terms of codon bias evolution. These network based findings not only recapitulates the established facts regarding the importance of each codon position in providing codon bias but also highlight their preferential role in resulting correlated mutations. Moreover, codon based nucleotide co-occurrence provides framework to investigate important evolutionary insights into human mitochondrial evolutionary genomics.

evolutionary biology↗