The Evolution of Lineage-Specific Regulatory Activities in the Human Embryonic Limb

Abstract

SUMMARY The evolution of human anatomical features likely involved changes in gene regulation during development. However, the nature and extent of human-specific developmental regulatory functions remain unknown. We obtained a genome-wide view of cis-regulatory evolution in human embryonic tissues by comparing the histone modification H3K27ac, which provides a quantitative readout of promoter and enhancer activity, during human, rhesus, and mouse limb development. Based on increased H3K27ac, we find that 13% of promoters and 11% of enhancers have gained activity on the human lineage since the human-rhesus divergence. These gains largely arose by modification of ancestral regulatory activities in the limb or potential co-option from other tissues and are likely to have heterogeneous genetic causes. Most enhancers that exhibit gain of activity in humans originated in mammals. Gains at promoters and enhancers in the human limb are associated with increased gene expression, suggesting they include molecular drivers of human morphological evolution.

High-resolution mapping of transcriptional dynamics across tissue development reveals a stable mRNA–tRNA interface

“…Here, we confirmed that liver and brain development are accompanied by thousands of protein-coding transcript changes, which accurately reflect the tissue and stage identity of all samples. Our gene expression data sets complement recent studies mapping enhancer deployment during mouse development (Cotney et al 2013;Nord et al 2013). The observed number of differentially expressed genes with respect to E15.5 gradually increased over developmental time, and corresponded to tissue and developmental stage-specific functions.…”

Deep homology in the age of next-generation sequencing

“…Hence, potential evolutionary modifications of enhancer activities have been the subject of intense investigation in the field of regulatory evolution. For example, using ChIP-seq for histone H3 lysine 27 acetylation (H3K27Ac), an active enhancer mark, the evolutionary and developmental dynamics of enhancer activities have been mapped in various different organs and across several taxonomic ranks [68][69][70]. Ideally, such enhancer activity maps will be complemented by the binding profiles of transcription factors known to be important for the development or function of the tissues in question [71,72].…”

Osmolality/salinity-responsive enhancers (OSREs) control induction of osmoprotective genes in euryhaline fish

“…Evolutionary differences in the environmental regulation of gene expression are often the result of altered cis-regulatory elements (CREs) (13,14). In fact, genetic variation in CREs and/or transacting factors represents an efficient and common evolutionary strategy for changing environmentally modulated gene-expression patterns (15)(16)(17)(18).…”