DNA mutations found to be biased toward favoring 'G-C' content. To make the iconic, twisted double helix that accounts for the diversity of life, DNA rules specify that G always pairs with C, and A with T. But, when it's all added up, the amount of G+C vs A+T content among species is not a simple fixed percentage or, standard one-to-one ratio.

In single-celled eukaryotes, yeast contains 38% G+C content, plants like corn have 47%, and humans contain about 41%. "This has been one of the long-standing problems in genome evolution, and prior attempts to explain it have involved considerable arm waving," said Michael Lynch, who leads a new Center for Mechanisms of Evolution.

"In the absence of key observations on the mutation process, there has been a struggle to fathom what the mechanism is," said Lynch. Researchers now experimentally demonstrated that G+C composition is generally strongly favored, whereas this is often opposed by mutational pressure of various strengths in the opposite direction.

"On average, natural selection or some other factor favors G+C content, regardless of the class of DNA, size of a species' genome, or where the species is found on the evolutionary tree of life," said Lynch. The study was published in the journal Nature Ecology and Evolution.

Driving evolution are DNA mutations, errors in the genome that are introduced and passed along to the next generation, so that over time, providing the fuel for the invention of new adaptations or traits.

To get to the heart of the matter, the scientists wanted a way to quantify the full spectrum of DNA mutations in the lab across a wide swath of species. This can now be done due in part by new technologies to make DNA sequencing faster and cheaper. It has fueled a golden age of evolutionary experimental biology.

"We started with knowledge of the mutational spectrum that occurs at the genome level in about 40 species examined in my lab," said Lynch. In a tour de force experiment that is the largest survey to date, they examined every single DNA mutation across different species, sequencing billions of DNA chemical bases.

"This represented a very substantial work load, effort and cost that were necessary to test different evolutionary models with high statistical power," said Hongan Long.

They also took advantage of an analysis of 25 current datasets of mutations and 12 new mutation-accumulation (MA) experiments (many from their own lab), including bacteria and a menagerie of multicellular organisms including yeast, worms, fruit flies, chimpanzees and humans.

During each MA experiment, they performed complete genome sequencing of about 50 different bacterial lines that had been passaged through severe, single-cell bottlenecks for thousands of cell divisions.

With each generation, they carefully measured the mutation rate, or every occurrence of when just a single DNA letter is changed. This can happen in two ways: a single G or C DNA base pair being converted to the A+T direction; or the opposite can happen, with an A or T base switching in the G+C direction.

After all the number and data crunching, a striking pattern emerged between G+C content and the expectations based on DNA mutations.