Genes are only 2% of Human DNA: What About the Rest?

Humans have a lot of "extra" DNA beyond what is contained in the 30,000 or so genes in the genome. Scientists expected humans to have 100,000 or more genes, given the complexity of the human organism. What is all that extra DNA doing? According to this report from news-medical.net, the worldwide race is on to locate the small DNA sequences that participate in the control of the "turning on" and "turning off" of genes.

Growing knowledge of how regulatory sequences control gene behavior has the potential to create new classes of treatment for nerve disorders and heart failure. Such sequences may also help to explain why humans are so complex, despite having one-fifth as much genetic material as wheat for instance. Medical center researchers are working on just one of more than 100 regulatory sequences identified so far, each the subject of intense study.

"Most people don't realize that genes make up a very small percentage of the human DNA code," said Joseph M. Miano, Ph.D., senior author of the journal paper and associate professor within the Cardiovascular Research Institute at the medical center. "Genes are relatively straightforward compared to what lies ahead. We believe that the real genetic gymnastics, the real intelligence of our system, is controlled by tiny bits of genetic material that tell genes what to do."

....Researchers also concluded that genes, specific batches of code that direct protein construction, comprise just about 2 percent of all human DNA. A central question in genetics has become: what does the remaining 98 percent of human genetic material do?

Regulatory sequences are emerging as an important part of the non-gene majority of human genetic material, once thought of as "junk DNA." A new frontier in genetic research is the defining of the regulome, the complete set of DNA sequences that regulate the behavior of genes. DNA segments that code for proteins average 200 base pairs in length, whereas regulatory sequences typically include just six to 10 base pairs, making them hard to find.

....In Miano's study, the regulatory sequence under examination was the CArG box. The nucleotide building blocks of DNA chains may contain any one of four nucleobases: adenine (A), thymine (T), guanine (G) and cytosine (C). Any sequence of code starting with 2 Cs, followed by any combination of 6 As or Ts, and ending in 2 Gs is a CArG box.

According to Miano, there are 1,216 variations of CArG box that together occur approximately three million times throughout the human DNA blueprint.

....When a piece of genetic material, gene or regulatory segment, is conserved by evolution from mice to humans it suggests that the segment has a valuable function. Miano's screen required that CArG boxes shared by humans and mice be included in his expanded version of the CarGome. CArG boxes identified by the computer screen were then tested to see if they indeed interacted with SRF and changed the behavior of genes as predicted.

This approach resulted in the disclosure of more than 100 hypothetical CArG boxes and the same number of genes previously unknown to be targeted by CArG-SRF. Of those, 60 CArG boxes have been validated as exerting influence over a gene.

....In the larger picture, regulatory sequences may help to explain why humans have just 25,000 genes when, given the degree of human complexity, researchers had expected to find more than 100,000. Regulatory sequences may be part of the answer because they enable a single gene to produce the same protein at different times, places and concentrations with subtly different roles.

"Humans share about one quarter of their genes with fish," Miano said. "Something must be at work to explain why we are so many times more complex. Regulatory sequences offer one of several emerging explanations for how we do more with fewer genes."

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Mapping the genome was only the start of the solving of the puzzle. Now we have to learn how the whole Rube-Goldberg device really works.