Novelty versus innovation of gene regulatory elements in human evolution and disease

It is not currently understood how much of human evolution is due to modifying existing functional elements in the genome versus forging novel elements from nonfunctional DNA. Many early experiments that aimed to assign genetic changes on the human lineage to their resulting phenotypic change have focused on mutations that modify existing elements. However, a number of recent studies have highlighted the potential ease and importance of forging novel gene regulatory elements from nonfunctional sequences on the human lineage. In this review, we distinguish gene regulatory element novelty from innovation. We propose definitions for these terms and emphasize their importance in studying the genetic basis of human uniqueness. We discuss why the forging of novel regulatory elements may have been less emphasized during the previous decades, and why novel regulatory elements are likely to play a significant role in both human adaptation and disease.