A genomic dominion with regulatory dependencies on human-specific single-nucleotide changes in Modern Humans

TL;DR

This study identifies thousands of human-specific regulatory genetic changes linked to a wide range of traits, diseases, and developmental processes, revealing their crucial role in human evolution and health.

Contribution

It provides a comprehensive analysis of human-specific regulatory single-nucleotide changes and their associations with diverse biological functions and diseases.

Findings

Over 8,400 genes linked with human-specific regulatory SNCs.

Significant enrichment in brain regions, tissues, and diseases.

Identification of genes related to inheritance and survival traits.

Abstract

Gene set enrichment analyses of 8,405 genes linked with 35,074 human-specific (hs) regulatory single-nucleotide changes (SNCs) revealed the staggering breadth of significant associations with morphological structures, physiological processes, and pathological conditions of Modern Humans. Significant enrichment traits include more than 1,000 anatomically-distinct regions of the adult human brain, many different types of human cells and tissues, more than 200 common human disorders and more than 1,000 records of rare diseases. Thousands of genes connected with regulatory hsSNCs have been identified in this contribution, which represent essential genetic elements of the autosomal inheritance and survival of species phenotypes: a total of 1,494 genes linked with either autosomal dominant or recessive inheritance as well as 2,273 genes associated with premature death, embryonic lethality, as well as pre-, peri-, neo-, and post-natal lethality of both complete and incomplete penetrance. Therefore, thousands of heritable traits and critical genes impacting the offspring survival appear under the human-specific regulatory control in genomes of Modern Humans. These observations highlight the remarkable translational opportunities afforded by the discovery of genetic regulatory loci harboring hsSNCs that are fixed in humans, distinct from other primates, and located in differentially-accessible (DA) chromatin regions during human brain development.