Mutational 'hot spot' leads to adaptation in high-altitude birds

October 14, 2015 by Scott Schrage, University of Nebraska-Lincoln
Jay Storz. Credit: Craig Chandler/University Communications

New research led by the University of Nebraska-Lincoln and the University of New Mexico has pinpointed changes in a single, mutation-prone gene site that ultimately allow wrens to breathe easy in the rarefied air of the Andes.

Published Oct. 12 in the journal Proceedings of the National Academy of Sciences, the findings also suggest that a gene site's rate of mutation may influence whether it contributes to adaptive .

The authors concluded that when many can produce the same favorable change in a trait, natural selection often seizes upon those that occur at an especially high rate—an evolutionary equivalent of "first come, first served."

The team's study of Andean wrens examined evolutionary changes in the functional properties of hemoglobin, the protein that transports oxygen from the lungs to body tissue. Oxygen concentration falls as altitude rises, making the protein's ability to capture oxygen molecules especially critical among wrens and other animals that live at higher elevations.

"We know from previous research that there are many possible mutations that can produce an increase in hemoglobin's affinity for oxygen," said UNL co-author Jay Storz, a Susan J. Rosowski Professor of Biological Sciences. "However, the particular mutations that actually contribute to evolutionary changes in protein function may represent a biased, nonrandom subset of all possible mutations capable of producing the change.

"Our results suggest that variation in may be an important source of such bias."

Storz and his UNL colleagues came to the conclusion after analyzing blood samples from 140 house wren specimens that ornithologist Christopher Witt and fellow UNM researchers collected during an expedition to the Andes.

The UNL researchers isolated hemoglobin proteins from the , comparing those that had the specified mutation against those that did not. The team also engineered synthetic hemoglobin that featured only the mutation of interest. Storz and his colleagues found that synthetic proteins with the engineered mutation captured oxygen roughly 1 1/2 times better than those without it.

The researchers also measured the frequency of the affinity-enhancing mutation in highland versus lowland wrens, discovering that the mutation predominated only in the high-altitude population.

To test whether the altitudinal difference in mutation frequency was caused by natural selection, the team then examined patterns of variation at DNA sites scattered throughout the species' genome.

"The genomic analysis revealed that the level of altitudinal differentiation at that single mutational 'hot spot' is much larger than what we see across the genome as a whole," Storz said. "That pattern suggests that the site-specific differentiation was caused by that favored different protein variants in different elevation zones."

Explore further: Context crucial when it comes to mutations in genetic evolution, study reports

More information: Contribution of a mutational hot spot to hemoglobin adaptation in high-altitude Andean house wrens, www.pnas.org/cgi/doi/10.1073/pnas.1507300112

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SteveGinGTO
not rated yet Oct 15, 2015
This sounds like potentially a good thing for humans, if such a gene can be found and then manipulated. I live most of my life at under 1000 feet. Now I live at 6800 feet and have never adapted in 3 years. I'd LOVE a genetic treatment that allowed me to breathe better at my new altitude.

In addition, this might make it possible for mountain climbers to breathe like Sherpas in the Himalayas. If I was a mountain climber, I WOULD CERTAINLY be interested in such a genetic treatment.
JVK
1 / 5 (5) Oct 15, 2015
...there are many possible mutations that can produce an increase in hemoglobin's affinity for oxygen...


No, there are not. Mutations perturb protein folding. Ecological variation leads to ecological adaptation via nutrient uptake and the physiology of reproduction. That fact has been consistently demonstrated in hummingbirds, deer mice, and humans.

Hummingbirds: http://www.pnas.o...abstract
Deer mice: http://www.scienc...abstract
Humans: http://www.jstor..../4444260

Hemoglobin S differs from A in the substitution of just a single amino acid, valine in place of glutamic acid in the beta chain of the hemoglobin molecule.

All 1180+ human hemoglobin variants are attributed to amino acid substitution(s) in one of the two globin chains. Theorists who report the variants as if they were mutations have killed millions of people via ignorance of cell type differentiation.
Vietvet
5 / 5 (4) Oct 15, 2015
Significance

"Within a given gene, there may be many possible mutations that are capable of producing a particular change in phenotype. However, if some sites have especially high rates of mutation to function-altering alleles, then such mutations may make disproportionate contributions to phenotypic evolution. We report the discovery that a point mutation at a highly mutable site in the β-globin gene of Andean house wrens has produced a physiologically important change in the oxygenation properties of hemoglobin (Hb). The mutant allele that confers an increased Hb–O2 affinity is present at an unusually high frequency at high altitude. These findings suggest that site-specific variation in mutation rate may exert a strong influence on the genetic basis of phenotypic evolution."
http://www.pnas.o...07300112
Vietvet
5 / 5 (4) Oct 15, 2015
"Here, we report the discovery that a single point mutation at a highly mutable site in the βA-globin gene has contributed to an evolutionary change in hemoglobin (Hb) function in high-altitude Andean house wrens (Troglodytes aedon). Results of experiments on native Hb variants and engineered, recombinant Hb mutants demonstrate that a nonsynonymous mutation at a CpG dinucleotide in the βA-globin gene is responsible for an evolved difference in Hb–O2 affinity between high- and low-altitude house wren populations."
http://www.pnas.o...07300112
Vietvet
5 / 5 (4) Oct 15, 2015
"Moreover, patterns of genomic differentiation between high- and low-altitude populations suggest that altitudinal differentiation in allele frequencies at the causal amino acid polymorphism reflects a history of spatially varying selection. The experimental results highlight the influence of mutation rate on the genetic basis of phenotypic evolution by demonstrating that a large-effect allele at a highly mutable CpG site has promoted physiological differentiation in blood O2 transport capacity between house wren populations that are native to different elevations."
http://www.pnas.o...07300112

In your face JVK.
Vietvet
5 / 5 (4) Oct 16, 2015
"These results demonstrate that repeated changes in biochemical phenotype involve parallelism at the molecular level, and that mutations with indirect, second-order effects on Hb allostery play key roles in biochemical adaptation."
http://www.pnas.o...abstract]http://www.pnas.o...abstract[/url]

"Epistatic interactions between mutant sites in the same protein can exert a strong influence on pathways of molecular evolution."
http://www.pnas.o...abstract]http://www.pnas.o...abstract[/url]

Nothing in Biology Makes Sense except in the Light of Evolution
http://www.jstor....contents

Mutations, evolution------what point were you trying to make?

JVK
1 / 5 (4) Oct 17, 2015
The inability of theorists to distinguish the difference between a mutation and an amino acid substitution causes biologically uninformed science idiots to think they can challenge serious scientists.
Vietvet
5 / 5 (4) Oct 17, 2015
JVK's definition of a "serious scientist"=creationist. The problem with that definition is there is NO science in creationism.
JVK
1 / 5 (4) Oct 17, 2015
http://www.pnas.o...abstract

Excerpt: "...our results illustrate a detailed chain of events linking a chromosomal rearrangement to changes in overt social behavior."

There are no mutations in the detailed chain of events that link ecological variation to ecological adaptations manifested as morphological AND behavioral diversity. If you want to link mutations to hemoglobin variants across species, you are forced to consider how the variants (the amino acid substitutions) are fixed the organized genomes of species from microbes to man.

Are biologically uninformed science idiots claiming that fixation "evolves?"
anonymous_9001
5 / 5 (4) Oct 18, 2015
you are forced to consider how the variants (the amino acid substitutions) are fixed


Fixation means a variant has become present in all individuals of a species. Given that there are hundreds of hemoglobin variants, none of them have achieved fixation.
JVK
1 / 5 (4) Oct 18, 2015
Fixation of amino acid substitutions in different modern human populations is common. Hemoglobin S is one example that I use.

Please provide a link to support what your ridiculous misrepresentation of the term "fixation" means in the context of your past ridiculous claims about what Chelo et al., (2013) showed. http://www.nature...417.html

Didn't you claim that mutations were fixed in some species? Is fixation what you think led to the re-evolution of the bacterial flagellum over-the-weekend? If so, were mutations fixed in organized genomes or were amino acid substitutions fixed in the populations with the re-evolved flagellum?
JVK
1 / 5 (4) Oct 18, 2015
...there is NO science in creationism.


The creationists who linked viruses to all pathology cited: Molecular Clocks and the Puzzle of RNA Virus Origins http://jvi.asm.or...93.short

His monograph was cited 131 times. See also: https://scholar.g...893.full

Is anyone claiming that all this means there is no science in creationism? It shows there is nothing but pseudoscience in neo-Darwinian theory. So does the evidence presented as: Supercoiled DNA is far more dynamic than the 'Watson-Crick' double helix http://phys.org/n...lix.html

Rosalind Franklin challenged the Watson-Crick' double helix model based on her work with viruses. She seemed to intuitively know that RNA-mediated DNA repair was required, which meant that mutations could not lead to evolution. All serious scientists know that Franklin was right.
Vietvet
5 / 5 (3) Oct 18, 2015


Rosalind Franklin challenged the Watson-Crick' double helix model based on her work with viruses. She seemed to intuitively know that RNA-mediated DNA repair was required, which meant that mutations could not lead to evolution. All serious scientists know that Franklin was right.


@JVK

It's amazing how you see things that don't exist. There is a word for that, apophenia, you make links that don't exist in reality.
AGreatWhopper
3 / 5 (6) Oct 18, 2015
This is more evidence that it's more "survival of the most often" than "survival of the fittest".

Hell, look at JVK. He's not fit to for any real life purpose but instinctively thinks that just doing it over and over and over will get somewhere. Georgia creationist idiots. Hey, JVK, there's something we could pull together on. I want to see dueling made legal again. I'd sure love to meet a creationist on the field of honor.
anonymous_9001
5 / 5 (2) Oct 18, 2015
RNA-mediated DNA repair was required, which meant that mutations could not lead to evolution


Non-sequitur/false dichotomy. There's a happy medium between too much genomic stability and not enough.
AGreatWhopper
2 / 5 (4) Oct 18, 2015
This sounds like potentially a good thing for humans, if such a gene can be found and then manipulated. I live most of my life at under 1000 feet. Now I live at 6800 feet and have never adapted in 3 years. I'd LOVE a genetic treatment that allowed me to breathe better at my new altitude.

In addition, this might make it possible for mountain climbers to breathe like Sherpas in the Himalayas. If I was a mountain climber, I WOULD CERTAINLY be interested in such a genetic treatment.


No need, it's already available, thank the Denisovans.
Huerta-Sanchez, E (2014). "Altitude adaptation in tibetans caused by introgression of denisovan-like DNA". Nature 512: 194–197
JVK
1 / 5 (3) Oct 18, 2015
Re: All serious scientists know that Franklin was right.

See: https://www.youtu...youtu.be All About that Base (Meghan Trainor Parody)

Watch the words on the screen about bringing Franklin back, and at the end where they politely claim Neil deGrasse Tyson is a "big ass" -- based on the representations of what the base is in the Meghan Trainor original. Neil deGrasse Tyson is clearly a bass (get it?)
JVK
1 / 5 (3) Oct 18, 2015
https://en.wikipe...Franklin
After finishing her portion of the work on DNA, with her own research team at Birkbeck College, Franklin led pioneering work on the molecular structures of viruses, including tobacco mosaic virus and the polio virus.[10] Her team member, and later her beneficiary, Aaron Klug continued her research and went on to win the Nobel Prize in Chemistry in 1982. Had she been alive, she would very likely have shared that prize as well.

http://www.chemhe...lin.aspx
During Crick's long tenure at Cambridge, he made fundamental contributions to unlocking the genetic code. He and Sydney Brenner demonstrated that each group of three adjacent bases on a single DNA strand codes for one specific amino acid. He also correctly hypothesized the existence of "transfer" RNA, which mediates between "messenger" RNA and amino acids.
JVK
1 / 5 (3) Oct 18, 2015
http://www.nobelp...es/2015/

"The Nobel Prize in Chemistry 2015 was awarded jointly to Tomas Lindahl, Paul Modrich and Aziz Sancar "for mechanistic studies of DNA repair".

DNA repair is nutrient-dependent and RNA-mediated via gene duplication and RNA-mediated amino acid substitutions that are fixed in organized genomes of living genera via their physiology of reproduction.

The world has been populated by too many biologically uninformed science idiots and the anonymous fools here represent them.

They will kill us all with their ridiculous theories, which recently led one group to create a virus that more efficiently steals the energy all cell types need for differentiation in the context of the biophysically constrained nutrient-dependent chemistry of RNA-mediated protein folding.

Obviously, they did not create the virus from scratch. When you learn how they created it, you will be forced to face the facts about creation.
Captain Stumpy
5 / 5 (3) Oct 19, 2015
Mutations perturb protein folding
Except some can be beneficial- this is experimentally proven and validated
http://myxo.css.m...dex.html

http://extavourla...dex.html

The creationists who linked viruses to all pathology
there is NO SCIENCE in creationist & that is PROVEN
https://en.wikipe...Arkansas

They will kill us all with their ridiculous theories
fanaticism at it's finest, thanks for demonstrating why religion can't comprehend or cope with science, jk

oh... almost forgot
reported for promotion of PSEUDOSCIENCE and RELIGION/CREATIONIST dogma

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