The Human Genome Project (HGP) was initiated in 1990 and completed in 2003. It 
aimed to sequence the whole human genome. Although it represented an advance in 
understanding the human genome and its complexity, many questions remained 
unanswered. Other projects were launched in order to unravel the mysteries of 
our genome, including the ENCyclopedia of DNA Elements (ENCODE). This review 
aims to analyze the evolution of scientific knowledge related to both the HGP 
and ENCODE projects. Data were retrieved from scientific articles published in 
1990-2014, a period comprising the development and the 10 years following the 
HGP completion. The fact that only 20,000 genes are protein and RNA-coding is 
one of the most striking HGP results. A new concept about the organization of 
genome arose. The ENCODE project was initiated in 2003 and targeted to map the 
functional elements of the human genome. This project revealed that the human 
genome is pervasively transcribed. Therefore, it was determined that a large 
part of the non-protein coding regions are functional. Finally, a more 
sophisticated view of chromatin structure emerged. The mechanistic functioning 
of the genome has been redrafted, revealing a much more complex picture. 
Besides, a gene-centric conception of the organism has to be reviewed. A number 
of criticisms have emerged against the ENCODE project approaches, raising the 
question of whether non-conserved but biochemically active regions are truly 
functional. Thus, HGP and ENCODE projects accomplished a great map of the human 
genome, but the data generated still requires further in depth analysis. © 2016 
by The International Union of Biochemistry and Molecular Biology, 44:215-223, 
2016.