Human-specific loss of regulatory DNA and the evolution of human-specific traits

Thousands of candidate human-specific regulatory sequences (HSRS) have been identified, supporting the idea that unique to human phenotypes result from human-specific alterations of genomic regulatory networks. Here, conservation patterns analysis of 18,364 regulatory DNA segments comprising candidate HSRS was carried out using the most recent releases of the reference genomes’ databases of humans and nonhuman primates (NHP) and defining the sequence conservation threshold as the minimum ratio of bases that must remap of 1.00. Present analyses identified 5,535 candidate HSRS defined by either the acceleration of mutation rates on the human lineage or the functional divergence from chimpanzee that are highly conserved in NHP and appear to evolve by the exaptation of ancestral DNA pathway. This pathway seems mechanistically distinct from the evolution of regulatory DNA driven by the species-specific expansion of transposable elements. It is proposed that phenotypic divergence of Homo sapiens is driven by the evolution of human-specific genomic regulatory networks via at least 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.

Download Full-text

Human specific loss of olfactory receptor genes

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0535697100 ◽

2003 ◽

Vol 100 (6) ◽

pp. 3324-3327 ◽

Cited By ~ 175

Author(s):

Y. Gilad ◽

O. Man ◽

S. Paabo ◽

D. Lancet

Keyword(s):

Olfactory Receptor ◽

Specific Loss ◽

Olfactory Receptor Genes ◽

Human Specific

Download Full-text

Developmental loci harbor clusters of accelerated regions that evolved independently in ape lineages

10.1101/226019 ◽

2017 ◽

Author(s):

Dennis Kostka ◽

Alisha K. Holloway ◽

Katherine S. Pollard

Keyword(s):

Statistical Tests ◽

Regulatory Elements ◽

Altered Expression ◽

Evolutionary Forces ◽

Shared Set ◽

Accelerated Evolution ◽

Core Set ◽

Regulatory Dna ◽

Human Accelerated Regions ◽

Human Specific

AbstractSome of the fastest evolving regions of the human genome are conserved non-coding elements with many human-specific DNA substitutions. These Human Accelerated Regions (HARs) are enriched nearby regulatory genes, and several HARs function as developmental enhancers. To investigate if this evolutionary signature is unique to humans, we quantified evidence of accelerated substitutions in conserved genomic elements across multiple lineages and applied this approach simultaneously to the genomes of five apes: human, chimpanzee, gorilla, orangutan, and gibbon. We find roughly similar numbers and genomic distributions of lineage-specific accelerated regions (linARs) in all five apes. In particular, apes share an enrichment of linARs in regulatory DNA nearby genes involved in development, especially transcription factors and other regulators. Many developmental loci harbor clusters of nonoverlapping linARs from multiple apes, suggesting that accelerated evolution in each species affected distinct regulatory elements that control a shared set of developmental pathways. Our statistical tests distinguish between GC-biased and unbiased accelerated substitution rates, allowing us to quantify the roles of different evolutionary forces in creating linARs. We find evidence of GC-biased gene conversion in each ape, but unbiased acceleration consistent with positive selection or loss of constraint is more common in all five lineages. It therefore appears that similar evolutionary processes created independent accelerated regions in the genomes of different apes, and that these lineage-specific changes to conserved non-coding sequences may have differentially altered expression of a core set of developmental genes across ape evolution.

Download Full-text

Mechanistically Distinct Pathways of Divergent Regulatory DNA Creation Contribute to Evolution of Human-Specific Genomic Regulatory Networks Driving Phenotypic Divergence ofHomo sapiens

Genome Biology and Evolution ◽

10.1093/gbe/evw185 ◽

2016 ◽

Vol 8 (9) ◽

pp. 2774-2788 ◽

Cited By ~ 12

Author(s):

Gennadi V. Glinsky

Keyword(s):

Regulatory Networks ◽

Phenotypic Divergence ◽

Genomic Regulatory Networks ◽

Regulatory Dna ◽

Human Specific

Download Full-text

Effects of reference databases' refinements on the validity of molecular definitions of 15,371 candidate human-specific regulatory sequences

10.1101/026435 ◽

2015 ◽

Author(s):

Gennadi Glinsky

Keyword(s):

Regulatory Networks ◽

Regulatory Elements ◽

Regulatory Sequences ◽

Accurate Definition ◽

Reference Databases ◽

Definition Of ◽

Regulatory Dna ◽

Sequence Quality ◽

Human Specific

Thousands of candidate human-specific regulatory sequences (HSRS) have been identified, supporting the idea that unique to human phenotypes result from human-specific changes to genomic regulatory networks (GRNs). The sequence quality of reference genome databases is essential for the accurate definition of regulatory DNA segments as candidate HSRS. It is unclear how database improvements would affect the validity of the HSRS' definition. Sequence conservation analysis of 15,371 candidate HSRS was carried out using the most recent releases of reference genomes' databases of humans and nonhuman primates (NHP) defining the conservation threshold as the minimum ratio of bases that must remap of 1.00. This analysis identifies 3,793 regulatory DNA segments that lack evidence of human-specific mutations and represent regulatory sequences highly conserved in humans, Bonobo, and Chimpanzee. Present analysis revealed a major database refinement's effect on the validity of HSRS' definition and suggests that human-specific phenotypes may evolve as a results of integration into human-specific GRNs of both conserved in NHP and human-specific genomic regulatory elements.

Download Full-text