Enhancer Function and Evolutionary Roles of Human Accelerated Regions.

Bibliographic Collection: 
CARTA-Inspired Publication
Publication Type: Journal Article
Authors: Whalen, Sean; Pollard, Katherine S
Year of Publication: 2022
Journal: Annu Rev Genet
Volume: 56
Pagination: 423-439
Date Published: 2022 Nov 30
Publication Language: eng
ISSN: 1545-2948
Keywords: Animals, Animals, Genetically Modified, Genome, Human, Humans, Nucleotides

Human accelerated regions (HARs) are the fastest-evolving sequences in the human genome. When HARs were discovered in 2006, their function was mysterious due to scant annotation of the noncoding genome. Diverse technologies, from transgenic animals to machine learning, have consistently shown that HARs function as gene regulatory enhancers with significant enrichment in neurodevelopment. It is now possible to quantitatively measure the enhancer activity of thousands of HARs in parallel and model how each nucleotide contributes to gene expression. These strategies have revealed that many human HAR sequences function differently than their chimpanzee orthologs, though individual nucleotide changes in the same HAR may have opposite effects, consistent with compensatory substitutions. To fully evaluate the role of HARs in human evolution, it will be necessary to experimentally and computationally dissect them across more cell types and developmental stages.

DOI: 10.1146/annurev-genet-071819-103933
Alternate Journal: Annu Rev Genet