'Silent' Mutations

Patricia Clark Research Feature

Jessica Sieff | March 4, 2020

Proteins, the workhorse of the human cell, help digest our food, carry oxygen through the body, fight off invading microbes, and so much more — but they only function when folded properly into specific, three dimensional structures.

Misfolded proteins contribute to a number of diseases — including cystic fibrosis, juvenile cataracts, Alzheimer’s disease and many forms of cancer.

Scientists have long ignored half of all mutations in the genetic sequences of our DNA, called synonymous or “silent” mutations, because these mutations were thought to not affect the process by which amino acid sequences lead proteins to fold properly. Now, new research from the University of Notre Dame shows these silent mutations are worth a closer look.

“Synonymous mutations were long considered to be genomic background noise, but we found they do indeed lead to altered protein folding, and in turn impair cell function,” said Patricia Clark, the Rev. John Cardinal O’Hara professor of biochemistry at the University of Notre Dame, and lead author of the study. “Our results show that synonymous variations in our DNA sequences — which account for most of our genetic variation — can have a significant impact on shaping the fitness level of cellular proteins.”

Read more here. 

 by Daily Domer Staff