Partly human yeast show a common ancestor's lasting legacy

May 21, 2015
Baker's yeast growing on an agar plate. Credit: Rainis Venta. Image rights: Creative Commons Attribution-Share Alike 3.0.

Despite a billion years of evolution separating humans from the baker's yeast in their refrigerators, hundreds of genes from an ancestor that the two species have in common live on nearly unchanged in them both, say biologists at The University of Texas at Austin. The team created thriving strains of genetically engineered yeast using human genes and found that certain groups of genes are surprisingly stable over evolutionary time.

The research, published May 22 in the journal Science, paves the way for using humanized to better understand genetic disorders and to screen drugs for treating the diseases.

Although yeast consist of a single cell and humans have trillions of organized into complex systems, we share thousands of similar genes. Of those, about 450 are critical for yeast's survival, so researchers removed the yeast version of each one and replaced it with the version and waited to see whether the yeast would die. Creating hundreds of new strains of yeast, each with a single human gene, resulted in many newly engineered strains—nearly half, in fact—that could survive and reproduce after having human genes swapped in for their ordinary ones.

"Cells use a common set of parts and those parts, even after a billion years of independent evolution, are swappable," said Edward Marcotte, professor in the university's Department of Molecular Biosciences and co-director of the Center for Systems and Synthetic Biology (CSSB). "It's a beautiful demonstration of the common heritage of all living things—to be able to take DNA from a human and replace the matching DNA in a yeast cell and have it successfully support the life of the cell."

Edward Marcotte and his colleagues at the University of Texas at Austin created hundreds of strains of humanized yeast by inserting into each a single human gene and turning off the corresponding yeast gene. Credit: Jacqui Tabler

The work has applications for human health in that some caused by mutations could be tested in new ways. Future studies might compare different strains of humanized yeast, each with slightly different versions of the same human gene, to better understand how certain mutations affect a person's health. Researchers also could insert precise versions of a mutation into yeast and then expose the yeast to different drugs to test new therapies.

"We could find out if one of the standard treatments would work on your particular version of the gene or if maybe another drug would be even better," says Claus Wilke, a professor in the Department of Integrative Biology and co-author of the paper.

Marcotte speculates that there might be another 1,000 or so pairs of swappable genes between humans and yeast. Along with the approximately 200 swappable genes already identified, these might be useful in searching for drugs to treat a host of .

This kind of gene swap experiment between humans and yeast has been done for single genes before, but this is the first large-scale study to swap hundreds of gene pairs. The large number of tests allowed team member Jon Laurent, a graduate student in the CSSB and co-author of the paper, to look for underlying rules for what makes a gene swappable.

Surprisingly, the best predictor of whether two genes could be successfully swapped was not how similar their genetic sequences were, but rather which modules they were part of. A module is a group of genes that work together to do something useful, such as produce cholesterol to build cell walls. All the genes from the same module tended either to be swappable between humans and yeast, or not.

"This work is basically showing that you can take a fuel injector from a tractor and swap it for a fuel injector in your Toyota and it will still work, more or less, because they're both fuel injectors," Marcotte said.

"The exciting part is that we can now use this information to swap entire systems involving dozens of genes at a time and ask if that system works as well as the natural system in yeast," says Aashiq Kachroo, postdoctoral researcher in the CSSB and co-author of the paper. "That will be fascinating because now we won't be just looking at a gene, but 30 different from a human in a simple cell."

Explore further: New genetic tool helps researchers to analyze cells' most important functions

More information: Systematic humanization of yeast genes reveals conserved functions and genetic modularity, www.sciencemag.org/lookup/doi/10.1126/science.aaa0769

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JVK
2 / 5 (4) May 21, 2015
Excerpt: "Despite a billion years of evolution separating humans from the baker's yeast..."

If you start with a ridiculous assumption about the time it takes microbes to evolve into humans, you should attempt to explain ~2 billion years of no changes in bacteria living in sediment at the bottom of the ocean. http://phys.org/n...ars.html

You should then explain re-evolution of the bacterial flagellum "over-the-weekend." http://phys.org/n...tor.html

If you think the credibility of claims about billions of years of evolution and no evolution in 2 billion years and re-evolution of a complex functional structure in 4 days should be questioned, you are probably a serious scientist, not an evolutionary theorist.
JVK
2 / 5 (4) May 21, 2015
See also: http://phys.org/n...tml#nRlv Evolution of a natural gene network explored by Yale researchers

"We have little empirical evidence about how evolution occurs at the gene network level..." author of the study. "Elucidating the role played by negative-feedback regulation on cross-species network activity differences adds to our understanding."

Empirical evidence that links the biophysically constrained chemistry of nutrient-dependent RNA-mediated protein folding to cell type differentiation in all cells of all individuals of all genera suggest that claims about billions of years of evolution are absurd.

Metabolic networks and genetic networks are epigenetically linked from viruses and viral microRNAs to entropic elasticity. Without the anti-entropic epigenetic effect of nutrient-dependent microRNAs, metabolic networks could not be linked to biodiversity via genetic networks.
JVK
1 / 5 (3) May 21, 2015
https://answersin...esources Excerpt: "An estimated 1031 bacteriophages (ten thousand billion billion billion) fill the earth, and bacteriophages infect 1024 bacteria per second.1 There is a tremendous amount of genetic material flowing in and out of bacteria at any given time!"

This genetic material is placed into the context of information about the source of nutrients that link metabolic networks to genetic networks. Mathematical models link the biophysically constrained nutrient-dependent chemistry of protein folding from ecological variation to ecological adaptations via the physiology of reproduction.

https://www.quant...viruses/
Excerpt: Mathematical models of ocean ecosystems suggest that by killing so many microbes, viruses could release carbon and other organic nutrients back into the environment, providing an easy source of nutrients for other organisms.
JVK
1 / 5 (3) May 22, 2015
A universal trend of amino acid gain and loss in protein evolution
http://www.nature...306.html

Excerpt: "We cannot conceive of a global external factor that could cause, during this time, parallel evolution of amino acid compositions of proteins in 15 diverse taxa that represent all three domains of life and span a wide range of lifestyles and environments. Thus, currently, the most plausible hypothesis is that we are observing a universal, intrinsic trend that emerged before the last universal common ancestor of all extant organisms."

Mathematical models of ocean ecosystems do not suggest that anything besides viruses could link the nutrient-dependent biophysically constrained chemistry of RNA-mediated protein folding from metabolic networks to genetic networks in species from microbes to humans via conserved molecular mechanisms of biologically-based top-down causation and physiology of reproduction.
thingumbobesquire
1 / 5 (1) May 23, 2015
Natural selection is a bestial and racialist dogma based upon white colored skin's suitability for less sunny climates. This is why the subtitle of Darwin's doctrine of evolution is "the Preservation of Favoured Races in the Struggle for Life." The true nature of humanity's evolution is our species' unique and evolving power over the energetic forces of nature, starting with our control of fire. Today, we have control of nuclear fission, soon, if we don't outlaw scientific progress we will have control over thermonuclear fusion, and next in that sequence will be matter/anti-matter reactions. Thus there is a non-linear quantum leap in our species' potential to use ever more powerful sources of energy to expand our well being into the limitless future. You won't find this uniquely human quality in any genetic mechanism.

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