How the genetic blueprints for limbs came from fish

Jan 21, 2014
This shows the expression of fish Hox genes in a mouse embryo. Credit: Denis Duboule, UNIGE

A study led by Denis Duboule shows that limbs emerged during evolution by modernisation of a preexisting DNA structure.

Our first four-legged land ancestor came out of the sea some 350 million years ago. Watching a lungfish, our closest living fish relative, crawl on its four pointed fins gives us an idea of what the first evolutionary steps on land probably looked like. However, the transitional path between fin structural elements in fish and limbs in remains elusive.

Both fish and land animals possess clusters of Hoxa and Hoxd genes, which are necessary for both fin and limb formation during embryonic development. Denis Duboule's team, at the University of Geneva and the EPFL, Switzerland, compared the structure and behavior of these gene clusters in embryos from mice and zebrafish. The researchers discovered similar 3-dimensional DNA organization of the fish and mouse clusters, which indicates that the main genetic mechanism used to pattern tetrapod limbs was already present in fish. However, when inserted into transgenic mouse embryos, the fish Hox genes were only active in the mouse arm but not in the digits, showing that the fish DNA lacks essential genetic elements for digit formation. The study, publishing January 21, in the open access journal PLOS Biology, concludes that, although the digital part of the limbs appear first in land animals, this happened by elaborating on an ancestral, pre-existing DNA infrastructure in fish.

Duboule's team had recently shown that, during mammalian development, Hoxd genes depend on a 'bimodal' 3-dimensional DNA structure to direct the development of the characteristic subdivision of the limbs into 'arm' and 'hand', a division which is absent from .

"To determine where the genetics behind this subdivision into 'hand' and 'arm' came from during evolution, we decided to closely compare the genetic processes at work in both fin and limb development", says Joost Woltering, post-doc at the Department of Genetics and Evolution of the Science Faculty of the UNIGE and lead author of this study. Surprisingly, the researchers found a similar bimodal 3-dimensional chromatin architecture in the Hoxd gene region in zebrafish embryos. These findings indicate that the regulatory mechanism used to pattern tetrapod limbs probably predates the divergence between fish and tetrapods. "In fact this finding was a great surprise as we expected that this 'bimodal' DNA conformation was exactly what would make all the difference in the genetics for making limbs or making fins" adds Joost Woltering.

This is the Doboule PR Image. Credit: Denis Duboule

Does this imply that digits are homologous to distal fin structures in fish? To answer this question, the geneticists inserted into mice embryos the genomic regions that regulate Hox gene expression in fish fins. "As another surprise, regulatory regions from fish triggered Hox gene expression predominantly in the arm and not in the digits. Altogether, this suggest that our digits evolved during the fin to limb transition by modernization of an already existing regulatory mechanism", explains Denis Duboule.

The researchers conclude that, although fish possess the Hox regulatory toolkit to produce digits, this potential is not utilized as it is in tetrapods. Therefore, they propose that fin radials, the bony elements of fins, are not homologous to tetrapod digits, although they rely in part on a shared regulatory strategy.

New lines of investigation are to find out exactly what has changed in the DNA elements of versus tetrapods. "By now we know a lot of genetic switches from the mouse that drive Hox expression in the digits. It is key to find out exactly how these processes work nowadays to understand what made digits appear and favor the colonization of the terrestrial environment." concludes Duboule.

Explore further: The influence of the Isthmus of Panama in the evolution of freshwater shrimps in America

More information: Woltering JM, Noordermeer D, Leleu M, Duboule D (2014) Conservation and Divergence of Regulatory Strategies at Hox Loci and the Origin of Tetrapod Digits. PLoS Biol 12(1): e1001773. DOI: 10.1371/journal.pbio.1001773

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User comments : 18

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matt_roadhouse
1.4 / 5 (9) Jan 21, 2014
"Our first four-legged land ancestor came out of the sea some 350 million years ago"

After decades of research, Macro-evolution is still utterly unproven.

Why is something so far-fetched quoted like truth. Sure all life is coded in a 4 bit language ... but that's where the similarity ends.
verkle
1.3 / 5 (10) Jan 21, 2014
How the genetic blueprints for limbs came from fish...


I don't find anything in the article to provde such a statement.
Pure speculation.
Such statements don't belong on a science site.

Whydening Gyre
4.6 / 5 (9) Jan 21, 2014
So... I gather the two of you are not evolutionist in your "how we got here" world view?
Sinister1812
4.6 / 5 (7) Jan 22, 2014
And what about those fish that have "elbows" and walk on land, like the mudskipper? That should be proof enough.
Captain Stumpy
4.6 / 5 (7) Jan 22, 2014
@matt_roadhouse and verkle
WHY come to a science site to deny science? especially if you have no ability to refute it? no links, valid science, no proof!
You are what? Creationist?
religious?
Religion has no place in science
now... if you want to do some basic research and learn SOMETHING

http://www.visembryo.com/

go through the stages, read MORE research than just this tiny article

try to learn something
put your preconceived notions back in the box and leave your religion behind when talking science,

it has NO PLACE here and it is OFF TOPIC
matt_roadhouse
1 / 5 (3) Jan 22, 2014
Cpt. Stumpy:

I will read your link. The point is ... there is zero proof for anything related to macro-evolution

How do you support that via links etc.

I am agnostic, so no religion ... I take everything at face value. Seems maybe you have a large amount of preconceived notions though ...

http://www.newgeo...n32.html

About 30% into this article is goes very deep into biochemistry
shavera
5 / 5 (2) Jan 22, 2014
WHY come to a science site to deny science? especially if you have no ability to refute it? no links, valid science, no proof!


Because they know we'll feed the trolls. Look at every article everywhere. We're practically the troll soup kitchen up in here.
Captain Stumpy
5 / 5 (1) Jan 22, 2014
there is zero proof for anything related to macro-evolution

@matt_r
An example of macroevolution is the appearance of feathers during the evolution of birds from theropod dinosaurs.

https://en.wikipe...eopteryx

The evolutionary course of Equidae (wide family including all horses and related animals) is often viewed as a typical example of macroevolution

https://en.wikipe...volution

Seems maybe you have a large amount of preconceived notions though

not really
only ONE BIG ONE
and that is that religion has NO PLACE in science
matt_roadhouse
1 / 5 (3) Jan 22, 2014
Funny you keep mentioning religion when not one comment anywhere here quotes any dogma of any sort

Fossils would show an immense amount of transitional creatures instead of a very small set of bees/oysters/birds. The biggest counter argument in this is .... its too slow to show full transitions. Issue is, bodies don't just work for hundreds of generations on non-working organs/limbs etc. Everything in our body has a purpose, and these purposes are linked through thousands of networks via proteins, gene management systems, hormones etc.

We have fossil records with eons between them that show identical species with zero variation. That isn't proof though ? A few 'odd' imprints are. Keep believing the antiquated records from 1800s I guess.

Moving on ...

GG on quoting wikipedia !
Captain Stumpy
5 / 5 (1) Jan 22, 2014
you keep mentioning religion

@matt
twice:
1- my assumption: most anti-evolution are religious
2- stating my only preconceived notion
Fossils would show an immense amount of transitional creatures

assuming 100% of all living creatures that died were fossilized
which we know did not happen
its too slow to show full transitions

"Paleontology, evolutionary developmental biology, comparative genomics, and molecular biology contribute many advances relating to the patterns and processes that can be classified as macroevolution" [sic]

http://www.newwor...volution

quoting wikipedia

had links/references at the bottom
use them
is the encyclopedia more to your liking?
Says the same thing
dont mistake expedience for ignorance, especially if the references are good.

I am not going to do all the homework
post some references/links to support that it does NOT exist
Talk is CHEAP

then we can continue
thanks
matt_roadhouse
1 / 5 (4) Jan 22, 2014
That entire article describes how every single sub-theory within macro doesn't work.

The only thing it does is try and say is micro+macro are the same, and differentiating between is solely a ploy by ID theorists.

The recent study of Genetic Entropy and the degradation of 'higher form' genomes shows that life is even susceptible to the 2nd Law of Thermodynamics

Every study done on fruit flies have been fruitless ;) Thousands of generations, even tinkering and doing our own 'natural selection' and still nothing beneficial. Certainly not moving into another higher species.

Mutations only work if within sperm/ovum since that is what passes chromosomes to make the core DNA which every host cell will carry. Even if you mutated an entire organ via insertion of circular DNA, that would not be passed via heredity. (gene therapy)

There will always be natural selection via predation, disease and changing food sources .. and isolation which Darwin documented well. =!evolution
matt_roadhouse
1 / 5 (3) Jan 22, 2014
Some may think I am crazy ;)

But these theories are not just about Biology, they reach into the Cosmos. Everything is set in a perfect way of mathematics and beauty, form and function.

I honestly find it crazy to say every single facet of the cosmos and life is purely random.

ID:

Amino acid molecules that form proteins, and nucleotide molecules that form DNA and RNA resist combining at any temperature. To combine, they need the help of mechanisms in a living cell or a biochemist in an organic chemistry laboratory.

DNA is made of only right-handed versions of nucleotides, while proteins are made of only left-handed versions of amino acids. Yet any random chemical reaction that produced nucleotides or amino acids would make an equal mix of left and right-handed versions of each.
Even if the thousands of nucleotides needed to form a DNA molecule, or the hundreds of amino acids needed to form a protein molecule were able to combine from the mix, they would be a jumble of L+R
Captain Stumpy
5 / 5 (2) Jan 22, 2014
@matt_r
Every study done on fruit flies have been fruitles

nice pun
but not true
try looking at other than flies

http://phys.org/n...ral.html

http://phys.org/n...tml#nRlv

http://phys.org/n...ria.html

But these theories are not just about Biology, they reach into the Cosmos. Everything is set in a perfect way of mathematics and beauty, form and function

poetic, but lets keep to facts

do some more reading around
do more research

pay for the AAAS membership and get the magazine
might help you find what you are looking for

i am not entirely sure we are on the same page at this point
Whydening Gyre
5 / 5 (3) Jan 22, 2014
We have fossil records with eons between them that show identical species with zero variation.

I'm a bit confused as to what you are saying, so.... What do you mean by "identical species"?
aroc91
5 / 5 (3) Jan 23, 2014

I am agnostic, so no religion ... I take everything at face value. Seems maybe you have a large amount of preconceived notions though ...


You claim to be agnostic, but you beg the question of how you believe everything got here. If you're not a Christian, creationism can't be your alternative explanation, so what is it?
Whydening Gyre
5 / 5 (2) Jan 23, 2014

I am agnostic, so no religion ... I take everything at face value. Seems maybe you have a large amount of preconceived notions though ...


You claim to be agnostic, but you beg the question of how you believe everything got here. If you're not a Christian, creationism can't be your alternative explanation, so what is it?


Aroc,
A creation theory is not solely a Christian hallmark. All religions have one.
To be fair, you can say science is just attempting to provide a fuller (hopefully more accurate) explanation to the same question - it's own view of the how we got here...
aroc91
5 / 5 (2) Jan 23, 2014
I can only assume it's Christianity as it follows the trend of the rest of the Christian creationists that come here.
Whydening Gyre
5 / 5 (2) Jan 23, 2014
I can only assume it's Christianity as it follows the trend of the rest of the Christian creationists that come here.

A fair assumption, considering the majority of creation proselytizing on an English language site would be Western . With the dominant Western religious group being Christian.

You have to admit that the infinite number of complex interactions resulting in our existence that we are now aware of can be - daunting. Making it look in the bigger picture, random (it isn't, actually. It just APPEARS that way). This might be a result of being taught math from a "sequential" perspective vs a logarithmic one (the method the Universe uses).
Anyway, I can see how the creation perspective derived from the view that all these organized structures we observe seemingly form out of total randomness. Since that individual can't truly visualize a seeming infinity, his consciousness acquiesces to the "it must have been designed by someone smarter than us" paradigm.

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