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Gain and Loss of Amino Acids Detected Across All of Life
Computational biologists looking for improvements in the way scientists compare proteins across genomes have found an unexpected pattern of gain and loss in the basic building blocks of proteins that apparently leads back to the earliest life on Earth.
Shamil Sunyaev (left), Ivan Adzhubei, and their colleagues found the same surprising pattern of protein evolution across dozens of independently evolving species. (Photo by Steve Gilbert)
The evidence covers the most recent 10 million years. But, as their computers sort through the contemporary data sets, the researchers hear the echo of the original genome of the last universal common ancestor clicking into place more than 3.5 billion years ago. The glimpse back in time may be similar to the way astronomers can still detect vestiges of the Big Bang from the background cosmic radiation.
“The most plausible hypothesis is that we are observing a universal, intrinsic trend that emerged before the last common ancestor of all extant organisms,” says a team led by Shamil Sunyaev, HMS assistant professor of medicine and health sciences and technology at Brigham and Women’s Hospital. The study appeared in Nature online Jan. 19 (doi:10.1038/nature03306).
The researchers found a consistent loss of four amino acids in the protein-coding regions of 14 different bacteria, yeast, rodent, and primate genomes. Five amino acids, on the other hand, have been consistently gaining. The same nine amino acids have risen or fallen in human proteins.
Time’s
Arrow
Mutations happen, and amino acids occasionally come and go, but until
now scientists had assumed a certain symmetry through time. Gain a few
cysteines
one millennium;
lose a few the next. Eventually, scientists believed, the relative proportion
of amino acids remained fairly constant, and the proteins were in a state
of equilibrium over time.
Instead, the new study found, twice as many cysteines have leaped onto the independently evolving genomes as have jumped off. The relentless, irreversible process is more basic than natural selection, which accepts or rejects the mutations to sculpt the proteins into different amino acid configurations to suit each organism’s needs at the time.
IN Cysteine Methionine Histidine Serine Phenylalanine |
OUT Proline Alanine Glutamic acid Glycine |
Evolutionary winners and losers. In the last 10 million years, four of the oldest amino acids have been dropping out of proteins ranging from yeast to mammals, while five amino acids have been hopping on.
“The bigger surprise was that these trends in the increase or decrease were highly consistent in different kinds of organisms separated from each other by enormous gulfs of time, lifestyle, and biology,” said co-author Eugene Koonin, senior investigator at the National Center for Biotechnology Information (NCBI). “I personally found it beyond belief.”
For those who are keeping score, proline, alanine, glutamic acid, and glycine have significantly dropped in abundance, according to the new findings. Meanwhile, cysteine, methionine, histidine, serine, and phenylalanine have expanded their ranks.
“We are observing that all proteins in all of life are changing their amino acid composition and that the amino acid composition is not at equilibrium,” said co-author Fyodor Kondrashov, a doctoral student at the University of California, Davis. “Dinosaur proteins would have had a different amino acid composition than modern proteins.”
A Model Remade
This fundamental observation about molecular evolution arose from a question
posed by Sunyaev about three years ago. He wanted to refine the models
routinely used to compare protein sequences.
Typically, similar proteins within species or between species will contain some mismatching amino acids. In order to align sequences properly, the computers need an underlying model of the process of amino acid substitution, said first author I. King Jordan, NCBI staff scientist. The most frequently used models assume a symmetry that the researchers disproved with this paper.
To identify the amino acid dynamics of thousands of proteins, the researchers selected two closely related genomes, rat and mouse, and one more distantly related genome, human. If a rat has a serine at the same protein site where a human and mouse have a glycine, then researchers call the serine the new arrival. This conclusion is based on the assumption that Mother Nature avoids making genomic changes. The technique works only in relatively close genomes. In more distantly related genomes, such as bacteria and animals, several amino acid switches could have occurred in the long separation from their particular last common ancestor.
| “The most plausible hypothesis is that we are observing a universal, intrinsic trend that emerged before the last common ancestor of all extant organisms.” |
Next came the hard part: trying to make sense of the data. They saw no trend at the DNA level among amino acids composed of different trios of the four nucleotides A, G, T, and C. They could pinpoint no causal global environmental change, such as volcanoes, whose belches could promote more of the sulfur-rich amino acids.
But the researchers found other intriguingly consistent lines of evidence. Research on the origin of the genetic code suggests that the first amino acids, which had been plentiful in ancient genomes, correlate with the ones now dropping out of the genome at the highest rates. And some of the newest, underrepresented amino acids are catching up fast. The exception seems to be the most recent amino acids, tryptophan and tyrosine, which so far show no signs of being gained or lost.
The new study encompasses several ideas about the origins of life, both terrestrial and extraterrestrial. Some of the oldest amino acids have been found on meteorites, apparently carried from space. And these evolutionary dropouts also correspond to the handful of amino acids created when researchers repeatedly discharged electricity into a sealed chamber of inorganic compounds, showing that life could have arisen under the conditions believed to be present on the early Earth.
Ultimately, Sunyaev and his colleagues settled on the most logical explanation. “Our conclusion,” Koonan said, “which is open for debate, is that current changes in amino acid composition, including those occurring within the human population, reflect what happened in the evolution of the genetic code about 4 billion years ago on the planet.”
“If someone comes up with a different explanation, that would be great,” Sunyaev added.
Koonin is following up with analysis of viruses, which evolve faster, possibly from different origins, using different evolutionary rules. Sunyaev plans to build more sensitive sequence comparison methods that may help scientists better predict functional sites of proteins and effective sites of mutations.
—Carol Cruzan Morton