Browsing by Author "Sachin, Kumar et al"

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    Genomic-microbial coevolution in human development: chromosome 2 fusion, and human accelerated regions
    (Springer, 2026-04-24) Singh, Siddharth; Md Shahadab; Sachin, Kumar et al
    Human-specific traits arise from a confluence of genomic and ecological innovations. A unique telomere-to-telomere fusion of ancestral ape chromosomes produced human chromosome 2 (HSA2), reorganizing the genome and its regulatory landscape. In parallel, hundreds of Human Accelerated Regions (HARs), conserved elements with human-specific sequence changes, became developmental enhancers, and ancient retroviral insertions, namely, endogenous retroviruses (ERVs), were co-opted into promoters and enhancers. Here, we integrate comparative genomics, epigenomics, and host-microbiome co-evolution to propose a unified framework linking these factors to human evolution. We posit that the chromosome 2 fusion reshaped 3D genome architecture and gene regulation. HAR and endogenous retroviral sequences formed composite regulatory modules that drove innovations in cortex development, limb patterning, and immune function. Moreover, host-microbiome co-evolution is woven into this framework, with examples of microbiota-responsive HAR-ERV circuits influencing mucosal immunity, gut-brain signaling, and inflammation.