Phenotypic divergence of Homo sapiens is driven by the evolution of human-specific genomic regulatory networks via two mechanistically distinct pathways of creation of divergent regulatory DNA sequences

TL;DR

This study analyzes human-specific regulatory sequences, revealing two distinct evolutionary pathways—exaptation of conserved DNA and transposable element insertions—that drive phenotypic divergence in Homo sapiens.

Contribution

It identifies and characterizes two mechanistically distinct pathways for the creation of divergent regulatory DNA sequences in humans.

Findings

5,535 human-specific regulatory sequences identified

Distinct pathways: exaptation of conserved DNA and transposable element insertions

Supports two pathways driving human phenotypic divergence

Abstract

Thousands of candidate human-specific regulatory sequences (HSRS) have been identified, supporting the hypothesis that unique to human phenotypes result from human-specific alterations of genomic regulatory networks. Here, conservation patterns analysis of 18,364 candidate HSRS was carried out based on definition of the sequence conservation threshold as the minimum ratio of bases that must remap of 1.00. A total of 5,535 candidate HSRS were identified that are: i) highly conserved in Great Apes; ii) evolved by the exaptation of highly conserved ancestral DNA; iii) defined by either the acceleration of mutation rates on the human lineage or the functional divergence from nonhuman primates. The exaptation of highly conserved ancestral DNA pathway seems mechanistically distinct from the evolution of regulatory DNA segments driven by the species-specific expansion of transposable elements. Present analysis supports the idea that phenotypic divergence of Homo sapiens is driven by the evolution of human-specific genomic regulatory networks via two mechanistically distinct pathways of creation of divergent sequences of regulatory DNA: i) exaptation of the highly conserved ancestral regulatory DNA segments; ii) human-specific insertions of transposable elements.