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A recent study from Harvard’s Wyss Institute for Biologically Inspired Engineering has uncovered features of the genetic code that may end a long-standing controversy in molecular biology and revolutionize the way many drugs and biofuels are currently produced.
For a decade, scientists have struggled to understand how codons--specific letter sequences of nucleotides that represent amino acids--dictate protein production.
“A lot of things that appear trivial in genetic coding…are not very well understood,” said Harvard Medical School professor Daniel B. Goodman, a co-author of the study.
Researchers have offered theories to explain why certain codons allow for greater protein production than others. The “codon ramp hypothesis” attributes high protein production to the slowing down of the ribosomes that make proteins. The idea holds that codons at the beginning of genes act like a ramp on a highway in slowing down ribosomes that might otherwise crash into each other.
According to the Wyss Institute researchers, this hypothesis does not accurately explain the role of codons.
“It is the DNA itself—the structure—that [is] driving the difference [in protein production] and not the codons that the DNA is made into,” Goodman said.
Goodman’s team, which also included Harvard genetics professor George M. Church and Wyss Institute scientist Sriram Kosuri, separated the effect of rare codons from structural differences within the cell. Through the use of advanced sequencing technology, the researchers found that DNA bases with weaker structures are more conducive to protein production due to their decreased folding.
While the Wyss researchers did find that rare codons increase protein production 10 to 15 fold, their experiment showed that when the cell’s ribosome “highway” is empty, which should allow for faster production according to the “ramp” hypothesis, there is no difference in production.
The results, published in Science, have important implications for biotechnology, medicine, and culinary science, Goodman said. Researchers may now be able to optimize protein production by simply altering certain features at the beginning of a gene.
The researchers hope to extend their study to examine related issues such as the role of codons in other parts of the gene and the effects of environmental conditions on gene production.
For now, Goodman said that he is glad that the team’s research has contributed to “finally resolving” a mystery of protein production.
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