Biology subjects

Aqil, A.

Publications and source records attributed to Aqil, A..

3 recordsLinked to original sources

bioRxiv2024

Evolvability through segmental duplication follows species-specific dynamics

Segmental duplications are major drivers of evolutionary innovation, yet their dynamics across vertebrates remain poorly understood. Here, we identify segmental duplications from long-read sequenced genomes of 117 vertebrates and the starfish, generating the largest multi-species dataset of its kind. We find that vertebrate genomes show a higher propensity for tandem duplications than for interspersed duplications. However, when focusing only on subtelomeric regions, avian and mammalian genomes show the opposite propensity toward interspersed duplications. We also observe that, across vertebrates, tandem duplications tend to be larger than interspersed duplications. Next, we construct a segmental duplication network for each species, and use network-derived properties to quantify the duplication landscape for that species. Functional enrichment analysis of hyper-duplicated genes reveals a strong enrichment in platypus for pheromone response, driven by the expansion of the vomeronasal pheromone receptor V1R gene family. Overall, our results uncover the general properties of vertebrate segmental duplication, demonstrate the rapid evolution of segmental duplication landscapes, and highlight the utility of network-based approaches for studying genome evolution. SignificanceGene and regulatory region duplications are a fundamental source of evolutionary raw material. Here we generate segmental duplication calls from 117 vertebrate species. We find that vertebrate genomes have a bias towards tandem duplications relative to interspersed duplications. However, in the subtelomeric regions, birds and mammals exhibit an opposite bias toward interspersed duplications. Our analysis of segmental duplication networks demonstrate that duplication landscapes evolve rapidly, following species-specific rather than phylogenetic patterns. These findings indicate that the genomic architecture underlying segmental duplications is highly dynamic, uniquely shaping each lineages potential to adapt. Our study provides the most comprehensive view of vertebrate segmental duplications to date and establishes a network-based framework for studying genomic structural evolution.

evolutionary biology↗

bioRxiv2024

Switch-like Gene Expression Modulates Disease Susceptibility

A fundamental challenge in biomedicine is understanding the mechanisms predisposing individuals to disease. While previous research has suggested that switch-like gene expression is crucial in driving biological variation and disease susceptibility, a systematic analysis across multiple tissues is still lacking. By analyzing transcriptomes from 943 individuals across 27 tissues, we identified 1,013 switch-like genes. We found that only 31 (3.1%) of these genes exhibit switch-like behavior across all tissues. These universally switch-like genes appear to be genetically driven, with large exonic genomic structural variants explaining five ([~]18%) of them. The remaining switch-like genes exhibit tissue-specific expression patterns. Notably, tissue-specific switch-like genes tend to be switched on or off in unison within individuals, likely under the influence of tissue-specific master regulators, including hormonal signals. Among our most significant findings, we identified hundreds of concordantly switched-off genes in the stomach and vagina that are linked to gastric cancer (41-fold, p<10-4) and vaginal atrophy (44-fold, p<10-4), respectively. Experimental analysis of vaginal tissues revealed that low systemic levels of estrogen lead to a significant reduction in both the epithelial thickness and the expression of the switch-like gene ALOX12. We propose a model wherein the switching off of driver genes in basal and parabasal epithelium suppresses cell proliferation therein, leading to epithelial thinning and, therefore, vaginal atrophy. Our findings underscore the significant biomedical implications of switch-like gene expression and lay the groundwork for potential diagnostic and therapeutic applications.

bioinformatics↗

bioRxiv2022

Balancing selection on genomic deletion polymorphisms in humans

A key question in biology is why genomic variation persists in a population for extended periods. Recent studies have identified examples of genomic deletions that have remained polymorphic in the human lineage for hundreds of millennia, ostensibly owing to balancing selection. Nevertheless, genome-wide investigations of ancient and possibly adaptive deletions remain an imperative exercise. Here, we used simulations to show an excess of ancient allele sharing between modern and archaic human genomes that cannot be explained solely by introgression or ancient structure under neutrality. We identified 63 deletion polymorphisms that emerged before the divergence of humans and Neanderthals and are associated with GWAS traits. We used empirical and simulation-based analyses to show that the haplotypes that harbor these functional ancient deletions have likely been evolving under time- and geography-dependent balancing selection. Collectively, our results suggest that balancing selection may have maintained at least 27% of the functional deletion polymorphisms in humans for hundreds of thousands of years.

evolutionary biology↗