Genetic Toolkits and Multicellularity

The article about the evolutionary history of body size on Earth has raised some interest. Words like “latent evolutionary potential was realized”, “realize preexisting evolutionary potential” and" a major innovation in organismal complexity—first the eukaryotic cell and later eukaryotic multicellularity" seem to have raised a few eye brows. Are “latent”, “pre-existing”, “innovation” and “potential” the appropriate words?

From the following figure, the earliest multicellular (Grypania spiralis) eukaryotic fossil dates back ±1.6 billion years ago (bya) and at present the earliest evidence for eukaryotic cells is posited to have existed 1.68-1.78 bya, (perhaps 1.8 bya or possibly even 2.1 bya) (Figure 1).

Figure 1

The following tree is adapted from with the tentative dates for the origins of archaea and bacteria, eukaryotes, as well as the origins of multicellular body plans (>3 cell types) (Figure 2).*

Figure 2: Tree of life (Adapted from

As suggested by the paper, increases in cellular sizes roughly coincide with the alleviation of at least one environmental constraint, namely low atmospheric oxygen pressure. The origin of body plans (±0.6 bya) also seem to coincide with an increase in atmospheric pressure. Why could that be?

A look at hedgehogs
With about 6, 000 spines on their back, an excellent sense of smell, a running speed of 4.5 mph a normal heart rate of up to 19o bps and 10 bps during hibernation, hedgehogs are interesting little animals. Hedgehog (hh) genes are equally fascinating. The reason for the name of this gene is that a malfunctioning hh gene often results in the formation of small pointy projections on embryos, similar to that of a hedgehog. So what does it do?

The hh signaling pathway plays a fundamental role in cell pattrerning, cell proliferation and participates in the development of tissues and organs during the stages of animal development. It exerts its effect by influencing the transcription of many target genes in a concentration dependent manner.

Mechanism of action and signal transduction: Hints from hedgelings and hoglets
The hh protein comprises of two domains, namely the hedge domain (hedgling) and the hog domain (hoglet). The hedge domain acts as a ligand after processing and binds to a set of conserved receptors to activate downstream signal transduction pathways [1]. After transcription, the hh-gene undergoes a post-translational autocatalyzing editing process initiated by the hoglet resulting in the formation of the hedgling protein. Further processing of the hedgling occur and include the palmitoylation and sterolation (addition of cholesterol) of the ligand (Figure 3). Interestingly, hh proteins are the only examples of sterolation in contempory biology (more on that later) [2]. After processing, the hedgling ligand is transported through the Dispatched receptor where it binds to a specific lipd transport molecule (different in invertebrates and vertabrates) and is transported and binds to the 12-transmembrane protein called Patched. Internalisation of Patched alleviates the inhibitory effect of Patched on the 7-transmembrane protein Smoothened. This in turn activates the hedghog-related transcription factors (Gli in vertebrates and Ci in invertabrates) (Figure 3) [2]. This relatively simple pathway plays a crucial role in the unfolding of the developmental program in vertebrates and invertebrates.

Figure 3: Hedgehog signal transduction. The hedgehog protein is post-translationally modified through autocatalyzation and palmitate and cholesterol addition. Processed hedgelings are transported to the extracellular matrix through dispatched receptors and in turn transported by lipid transport molecules to bind to patched receptors. Binding of hedgling molecules to Patched receptor results in the subsequent activation of hedgehog mediated transcrition factors e.g. Gli in vertebrates and Ci in invertebrates.

With the knowledge of some of the proteins that play a part in hh-signal control, let’s look at the evolution and origin of some of the components. The following proteins can be used for BLAST.
Hedgling (Amphimedon Queenslanica)
Hoglet (Monosiga Ovata)
Patched (Ciona Intestinalis)
Dispatched (Ciona Intestinalis)
Suppresor of Fused (Sufu) (Ciona Intestinalis)
Smoothened (Ciona Intestinalis)
Fused (Drosophila)
Gli1 (Human) or Ci (Drosophila)
Kif27 (vertebrate) or Cos2 (Drosophila)

Using the InterProScan Tool with these sequences, the following results were obtained:
Hedgling: The oldest (phylogenetically) bona fide hedgeling found so far is in the genome of the sponge, Amphimedon Queenslanica. However, the structure of this domain is structurally homologous to the zinc-binding motif in bacterial D-alanyl-D-alanine carboxypeptidases (the same motif found in beta-lactamases and the various nylonase genes).
Hoglets: Hoglets are typical Intein (internal protein) proteins also known as HINTs (hedgehog inteins) [3]. Inteins are selfish DNA elements that are distributed accross all the domains of life [4].
Patched:"]Patched is a transmembrane protein with a sterol sensing domain (SSD) and is also distributed in all the domains of life.
Dispatched: Dispathed is also a transmembrane protein with a SSD and forms a subfamily of the sterol sensing receptors. Also present in all the domains of life.
Fused: Fused is kinase conserved in all the domains of life.
Suppresor of Fused (Sufu): Sufu yielded an interesting result. Acting as a suppressor of the hh-signaling pathway, it is limited to the bilaterians and cnidaria and bacteria. it seems to have been lost in other linages.
Smoothened (Frizzled domain, G-protein-coupled receptor (GPCR) domain): Smoothened contains a frizzled domain and a GPCR domain. The frizzled domain is limited to eukaryotes, while the GPCR domain is conserved in all the domains of life.
Gli1: This protein (and cos2) is transcription factor and hh-signaling converges to control the activity of this protein. It is a zinc-finger protein. While zinc-finger proteins are conserved in all domains of life, this particular protein seems to be limited to eukaryotes.
Kif27: Kif27 (and Cos2) is a kinesin-related protein (KRP). Kif27 appears to be functional molecular motor while Cos2 seems to have lost the ability to function as a motor protein. KRPs however are conserved accross all domains of life [5]. A conserved function of KRPs is to facilitate movement of vesicle along microtubules and one of the functions of Cos2 seems to be just that [6].

From the above, the following picture of the components of the hh-signaling toolkit can be drawn.

Figure 4: Origins of the parts in the hedgehog signaling pathway. (Red = absent, Orange = reasonable sequence and/or structural simlarity, Green = present, Graded green = part of the same family).*

Note that many of the components of the signaling pathway are present in various bacterial and archaeal lineages. Also note that the origin of multicellular body plans roughly coincide with an increase in atmospheric oxygen pressure as well as the first bona fide hedgling. Remember, hedglings are the only examples of post-translational sterolation (addition of cholesterol) of proteins in contempory biology. Why is this interesting? Well, oxygen is needed for cholesterol synthesis, more importantly, oxygen is needed for placing the hydroxyl group in the 3-position of cholesterol which plays a crucial role in subsequent transformations (including sterolation). Thus, while large parts of the hh-signaling pathway was present, a little extra oxygen was needed to unlock multicellular signaling capabilities of hedglings.

Therefore, words like “pre-existing”, “latent” and “potential” seem apt in describing the hedghog signaling pathway and the unfolding of multicellular body plans in relation to the increase in atmospheric oxygen pressure. “Innovation” perhaps not so much, seeing that only real innovation was bought on about by life itself namely the increase in atmospheric oxygen. This increase in atmospheric oxygen in turn seemed to have unlocked the pathways to multicellular body plans (>3 cell types).

Gene loss vs Innovation
Looking at the hh-signaling pathway, there seem to be very little innovation, and a lot of co-option of pre-existing information into new functions. Sufu was an interesting example of gene loss only to be co-opted later into a role in the hh-signaling pathway. With this in mind, what can one expect to find in the Last Universal Common Ancestor (LUCA)? Also consider the following. The Tetrahymena thermophila (alveolate) genome has been sequenced, and a number of genes that are absent in yeast (fungi), are found in amoeba, vertebrates, invertebrates as well as in the Tetrahymena genome. It paints the following picture (Figure 5) [7].

Figure 5: Genes present in Tetrahymena thermophila but absent in yeast indicate either convergnece in higher organisms or that the genes were present in the eukaryote common ancestor.

Intriguing questions can arise from these observations.
1) Why does an increase in atmospheric oxygen seem to have the effect of driving eukaryotic multilcellular life but not bacteria and archaea? Is an intrinsic and latent property present in this domain?
2) Gene loss vs innovation: How much gene loss and how much innovation (not just co-option) has occured from the LUCA? (Speculating)
3) Why did all the toolkit parts for the hh-pathway converge on a single sterolation pathway when so many other possibilities are available? Or is it the optimal possibility and random variation and selection processes used by life hit a global optimum?


  1. Matus DQ, Magie CR, Pang K, Martindale MQ, Thomsen GH. The Hedgehog gene family of the cnidarian, Nematostella vectensis, and implications for understanding metazoan Hedgehog pathway evolution. Dev Biol 2008; 313: 501-518.
  2. Bijlsma MF, Spek CA, Peppelenbosch MP. Hedgehog: an unusual signal transducer. Bioessays 2004; 26: 387-394.
  3. Perler FB. Protein splicing of inteins and hedgehog autoproteolysis: structure, function, and evolution. Cell 1998; 92: 1-4.
  4. Pietrokovski S. Intein spread and extinction in evolution. Trends Genet 2001; 17 465-472.
  5. Varjosalo M, Taipale J. Hedgehog: functions and mechanisms. Genes Dev 2008; 22: 2454-2472.
  6. Ogden SK, Ascano M Jr, Stegman MA, Robbins DJ. Regulation of Hedgehog signaling: a complex story. Biochem Pharmacol 2004; 67: 805-814.
  7. Eisen JA, Coyne RS, Wu M, Wu D, Thiagarajan M, Wortman JR. et al. Macronuclear genome sequence of the ciliate Tetrahymena thermophila, a model eukaryote. PLoS Biol 2006; 4: e286.

A few interesting observations:

1) Components of the multicellular signaling pathway (sonic-hedgehog) were present in ancestral lineages way before the emergence of multi-cellularity.

2) The origin of multi-cellular body plans roughly coincide with an increase in atmospheric oxygen pressure as well as the first bona fide hedgling.

3) Hedglings are the only examples of post-translational sterolation (addition of cholesterol) of proteins in contempory biology and oxygen is needed for cholesterol synthesis, more importantly, oxygen is needed for placing the hydroxyl group in the 3-position of cholesterol which plays a crucial role in subsequent transformations (including sterolation).

4) While large parts of the hedgehog-signaling pathway was present, a little extra oxygen was needed to unlock multicellular signaling capabilities of hedglings.

5) The increase in atmospheric oxygen was bought on about by life itself and this increase in atmospheric oxygen in turn seemed to have unlocked the pathways to multicellular body plans

And now this:
Oxygen Key To ‘Cut And Paste’ Of Genes

ScienceDaily (July 12, 2009) — An oxygen-sensitive enzyme has been found to play a key role in how genes create the many different proteins that make up our bodies.
The finding shows that the enzyme, termed Jmjd6, directly intervenes in the process in which the DNA of our genes is ‘cut and pasted’ into instructions for the creation of specific proteins.

The discovery, reported in this week’s Science by a team led by scientists from Oxford University and Ludwig-Maximilians-University, Munich, opens up a new area of molecular research into conditions such as heart disease and cancer.

‘Previous work from Oxford has shown that some of these enzymes, called oxygenases, affect which genes are expressed in response to low levels of oxygen. What we have now found is that they also regulate the specific form this expression takes – to give the different proteins that make up everything from heart cells to tumours,’ said Professor Chris Schofield of Oxford University’s Department of Chemistry, one of the authors of the paper.

Genes, stored in the form of DNA, are converted into proteins by a ‘middleman molecule’ called Messenger Ribonucleic Acid – or ‘mRNA’.

Individual genes can often give rise to many different proteins because of a process known as mRNA splicing which enables the cutting and pasting of the mRNA that is produced from DNA. The proteins that the new oxygenase, termed Jmjd6, acts on are involved in regulating the ‘cutting and pasting’ process.

Angelika Böttger, who led the Munich group, said: ‘The discovery of a role for an oxygenase in mRNA splicing reveals that it is very likely that oxygen levels are involved in regulating almost all steps in the process of gene expression. The challenge now is to determine how the pattern of genes changes in different environments when oxygen is in short supply, enabling us to tackle important questions such as “why do tumour cells respond differently to low oxygen levels than normal cells?”'

A little more about the protein:

This gene encodes a nuclear protein with a JmjC domain. JmjC domain-containing proteins are predicted to function [B]as protein hydroxylases or histone demethylases.[/B] This protein was first identified as a putative phosphatidylserine receptor involved in phagocytosis of apoptotic cells; however, subsequent studies have indicated that it does not directly function in the clearance of apoptotic cells, and questioned whether it is a true phosphatidylserine receptor. Multiple transcript variants encoding different isoforms have been found for this gene.
Present where? Well, all over it seems, even proteobacteria (one of the most primitive groups of organisms:

From the opening post;
Therefore, words like “pre-existing”, “latent” and “potential” seem apt in describing the hedghog signaling pathway and the unfolding of multicellular body plans in relation to the increase in atmospheric oxygen pressure. “Innovation” perhaps not so much, seeing that only real innovation was bought on about by life itself namely the increase in atmospheric oxygen. This increase in atmospheric oxygen in turn seemed to have unlocked the pathways to multicellular body plans (>3 cell types).

A new article strenghtens this view of evolution whereby pre-existing pathways unfold into their potential roles in the emergence of multicellular body plans, thereby biasing evolutionary trajectories towards a few ends.
The Hedgehog Signaling Pathway: Where Did It Come From?

Figure 3. A parsimonious scenario for the evolution of the Ptc/Smo system.
We hypothesize that during the transition to multicellularity, a pre-existing lipid homeostasis system took on a new function in signaling. Initially, an ancient lipid transporter diversified; one of its descendents came under the transcriptional control of a GPCR that sensed the same lipid (i.e., forming a negative homeostatic feedback loop). Then, the fortuitous addition of a protein moiety to the lipid in question brought the system under the control of gene expression; a neighboring cell could now secrete the lipid at will (by coupling it to the protein moiety). Because the combined lipid–protein molecule would block the transporter, this meant that the sending cell was capable of changing the perceived homeostatic state of the receiving cell, which would have established a graded (quantitative) mode of cell–cell communication.


Figure 4: Origins of the parts in the hedgehog signaling pathway. (Red = absent, Orange = reasonable sequence and/or structural simlarity, Green = present, Graded green = part of the same family, Brown = unsure.).
Bigger pic here.

Note that many of the components of the signaling pathway are present in various bacterial and archaeal lineages. Also note that the origin of multicellular body plans roughly coincide with an increase in atmospheric oxygen pressure as well as the first bona fide hedgling. Remember, hedglings are the only examples of post-translational sterolation (addition of cholesterol) of proteins in contempory biology. Why is this interesting? Well, oxygen is needed for cholesterol synthesis, more importantly, oxygen is needed for placing the hydroxyl group in the 3-position of cholesterol which plays a crucial role in subsequent transformations (including sterolation). Thus, while large parts of the hh-signaling pathway was present, a little extra oxygen was needed to unlock multicellular signaling capabilities of hedglings.

And now note information from the above article:

Complex body plans require sophisticated cell–cell signaling pathways. How these pathways evolved is often not very well understood. Here, we argue that the Hedgehog (Hh) signaling pathway [B]may have arisen from systems that were originally designed for the transport and homeostasis of certain bacterial sterol analogs—the hopanoids.[/B]
We assume that the original function of Ptc was simply to transport an unwanted lipid molecule out of the cell. Smo, on the other hand, derives from a protein family whose main function is to sense and to transduce extracellular signals (i.e., the GPCR family). Therefore, we propose the following scenario: let us imagine that, in primitive eukaryotes, Smo was initially a receptor sensing lipid molecules and was acting upstream of the primitive Ptc transporter (Figure 3). The two molecules would have formed a simple homeostasis system; Smo would sense the abundance of a certain lipid and would transcriptionally induce Ptc whenever this lipid was in excess and needed to be removed from the membrane (i.e., pumped away). [B]We propose that when multicellular organisms arose, this system was available and was recruited for a new purpose: cell-to-cell signaling.[/B]

[B]The intriguing homology between components of lipid homeostasis pathways and components of the Hh signaling pathway leads to the hypothesis that the central membrane–players of the Hh signaling cascade—Smo and Ptc—evolved from a pre-existing lipid-sensing/homeostasis pathway.[/B] We propose a model of simple evolutionary steps, which posits that Ptc acts by pumping an activator of Smo, rather than an inhibitor. This scenario is compatible with most experimental data so far. The step-wise construction of pathways from older, [B]pre-existing modules is turning out to be a general theme in developmental biology[/B] [24].</blockquote>

The similarities between evolution and development are striking indeed… biased towards a few endpoints through random variation and selection.
And articles to show how and why:
1) Parallels between evolution and development:
Getting beyond the population genetics/developmental biology split: A New Evolutionary Synthesis

2) A few endpoints (small subset, limited variation) out of all the possible endpoints:
An End to Endless Forms: Epistasis, Phenotype Distribution Bias, and Nonuniform Evolution

3) Evolution learns:
Facilitated Variation: How Evolution Learns from Past Environments To Generalize to New Environments

4) And proteins control evolution:
Evolution’s new wrinkle: Proteins with cruise control provide new perspective

How does this prove your god?

Mmm, looks like cut and paste is too easy these days. Let me try:
Please guys, this is not productive at all. Irreverend, you are quadruple posting and Mechanist you are mass cross posting without making any useful arguments. Please don’t reply to this post - start a new thread or PM/email privately.

Mea culpa, mea maxima culpa. Guilty as charged, no argument, although it felt more like four billion of the same. And the question hasn’t been answered please note. But I am guilty in response to what, exactly? I understand quite well that you walk a tricky line as forum admin but this Mechanist dude has an unsavory history here (but mostly elsewhere) that is longer than … well, a very exceedingly long thing. He has proven himself time and again, through and through to be a deceiver, a BS artist, a poseur with an odious agenda for which no ruse, no trickery, no guile is too slimy if it serves his ends. He’s an intellectual goon without humility or honor, a fucking liar. That’s as delicate as I know how to put it. And that doesn’t gel with skepticism. At least not in my book it doesn’t because - and correct me if I’m wrong here - skepticism is first and foremost about intellectual honesty.

But if that’s unwelcome I’ll bow to the majority feeling of the forum.

(Consider this post duplicated also here, here and here.)

I would like to remind you of the first rule here:
Responses like the one rwenzori gave in this topic is much more appropriate. :wink:
This thread is for discussion of the subject headed above - if you have a problem with the poster, you are welcome to start a new thread elsewhere.

So, oxygen helped multicellular life along, but phospohrus played its role as well:

Did Phosphorus Trigger Complex Evolution – And Blue Skies?

ScienceDaily (May 11, 2010) — The evolution of complex life forms may have gotten a jump start billions of years ago, when geologic events operating over millions of years caused large quantities of phosphorus to wash into the oceans. According to this model, proposed in a new paper by Dominic Papineau of the Carnegie Institution for Science, the higher levels of phosphorus would have caused vast algal blooms, pumping extra oxygen into the environment which allowed larger, more complex types of organisms to thrive.
"Phosphate rocks formed only sporadically during geologic history," says Papineau, a researcher at Carnegie's Geophysical Laboratory, "[b]and it is striking that their occurrences coincided with major global biogeochemical changes as well as significant leaps in biological evolution."[/b]

In his study, published in the journal Astrobiology, Papineau focused on the phosphate deposits that formed during an interval of geologic time known as the Proterozoic, from 2.5 billion years ago to about 540 million years ago. “This time period is very critical in the history of the Earth, because there are several independent lines of evidence that show that oxygen really increased during its beginning and end,” says Papineau. The previous atmosphere was possibly methane-rich, which would have given the sky an orangish color. “So this is the time that the sky literally began to become blue.”

During the Proterozoic, oxygen levels in the atmosphere rose in two phases: first ranging from 2.5 to 2 billion years ago, called the Great Oxidation Event, when atmospheric oxygen rose from trace amounts to about 10% of the present-day value. Single-celled organisms grew larger during this time and acquired cell structures called mitochondria, the so-called “powerhouses” of cells, which burn oxygen to yield energy. The second phase of oxygen rise occurred between about 1 billion and 540 million years ago and brought oxygen levels to near present levels. This time intervals is marked by the earliest fossils of multi-celled organisms and climaxed with the spectacular increase of fossil diversity known as the “Cambrian Explosion.”

Papineau found that these phases of atmospheric change corresponded with abundant phosphate deposits, as well as evidence for continental rifting and extensive glacial deposits. He notes that both rifting and climate changes would have changed patterns of erosion and chemical weathering of the land surface, which would have caused more phosphorous to wash into the oceans. Over geologic timescales the effect on marine life, he says, would have been analogous to that of high-phosphorus fertilizers washed into bodies of water today, such as the Chesapeake Bay, where massive algal blooms have had a widespread impact.

“Today, this is happening very fast and is caused by us,” he says, “and the glut of organic matter actually consumes oxygen. But during the Proterozoic this occurred over timescales of hundreds of millions of years and progressively led to an oxygenated atmosphere.”

“This increased oxygen no doubt had major consequences for the evolution of complex life. It can be expected that modern changes will also strongly perturb evolution,” he adds. “However, new lineages of complex life-forms take millions to tens of millions of years to adapt. In the meantime, we may be facing significant extinctions from the quick changes we are causing.”

The research was supported by the Geophysical Laboratory of the Carnegie Institution for Science, Carnegie of Canada, and from the Fonds québécois pour la recherche sur la nature et les technologies (FQRNT), NASA Exobiology and Evolutionary Biology Program, and the NASA Astrobiology Institute through Cooperative Agreement NNA04CC09A.

At least two ingredients needed for multicellular life was produced in abundance by… life.

Origins of Multicellularity: All in the Family

ScienceDaily (July 9, 2010) — One of the most pivotal steps in evolution-the transition from unicellular to multicellular organisms-may not have required as much retooling as commonly believed, found a globe-spanning collaboration of scientists led by researchers at the Salk Institute for Biological Studies and the US Department of Energy's Joint Genome Institute
[b]A comparison of the genomes of the multicellular algae Volvox carteri and its closest unicellular relative Chlamydomonas reinhardtii revealed that multicellular organisms may have been able to build their more [u]complex molecular machinery largely from the same list of parts that was already available to their unicellular ancestors.[/u][/b]

“If you think of proteins in terms of lego bricks Chlamydomonas already had a great lego set,” says James Umen, Ph.D., assistant professor in the Plant Molecular and Cellular Biology Laboratory at the Salk Institute. “Volvox didn’t have to buy a new one, and instead could experiment with what it had inherited from its ancestor.”

Altogether the findings, published in the journal Science, suggest that very limited protein-coding innovation occurred in the Volvox lineage. “We expected that there would be some major differences in genome size, number of genes, or gene families sizes between Volvox and Chlamydomonas,” says Umen. “Mostly that turned out not to be the case.”

The evolution of multicellularity occurred repeatedly and independently in diverse lineages including animals, plants, fungi, as well as green and red algae. “This transition is one of the great evolutionary events that shaped life on earth,” says co-first author Simon E. Prochnik, Ph.D., a Computationial Scientist at the DOE Joint Genome Institute. “It has generated much thought and speculation about what makes multicellular organisms different or more complex than their unicellular ancestors.”

In most cases the switch from a solitary existence to a communal one happened so long ago-over 500 million years-that the genetic changes enabling it are very difficult to trace. An interesting exception to the rule are volvocine green algae. For them, the transition to multicellularity happened in a series of small, potentially adaptive changes, and the progressive increase in morphological and developmental complexity can still be seen in contemporary members of the group (see slide show).

Volvox, the most sophisticated member of the lineage, is believed to have evolved from a Chlamydomonas-like ancestor within the last 200 million years, making the two living organisms an appealing model to study the evolutionary changes that brought about multicellularity and cellular differentiation.

To gather data for the comparative genomic analysis, the researchers sequenced the 138 million base pair Volvox genome using a whole genome shotgun strategy. The genome itself is 17% larger than the previously sequenced genome of Chlamydomonas and the sequence divergence between the two is comparable to that between human and chicken.

Despite the modest increase in genome size, the number of predicted proteins turned out to be very similar for the two organisms (14,566 in Volvox vs. 14,516 in Chlamydomonas) and no significant differences could be identified in the repertoires of protein domains or domain combinations. Protein domains are parts of proteins that can evolve, function, and exist independently of the rest of the protein chain.

“This was somewhat unexpected,” explains Umen, “since innovation at the domain level was previously thought to play a role in the evolution of multicellularity in the plant and animal lineages.”

In contrast to the overall lack of innovation, protein families specific to volvocine algae, such as extracellular matrix proteins, were enriched in Volvox compared to Chlamydomonas. Each mature Volvox colony is composed of numerous flagellated cells similar to Chlamydomonas, which are embedded in the surface of a spheroid of elaborately patterned extracellular matrix (ECM) that is clearly related to the Chlamydomonas cell wall. Maybe not surprisingly, the difference in size and complexity between the Volvox extracellular matrix and Chlamydomonas cell wall is mirrored by a dramatic increase in the number and variety of Volvox genes for two major ECM protein families, pherophorins and VMPs.

Additionally, Umen and his collaborators identified an increase in the number of cyclin D proteins in Volvox, which govern cell division and may be necessary to ensure the complex regulation of cell division during Volvox development. Last but not least, Volvox adapted a few of its existing genes to acquire novel functions. Members of the pherophorin family, for one, not only help build the extracellular matrix; some subtypes evolved into a diffusible hormonal trigger for sexual differentiation.

Researchers who also contributed to this work include Alan Kuo, Uffe Hellsten, Jarrod Chapman, Astrid Terry, Jasmyn Pangilinan, Asaf Salamov, Harris Shapiro, Erika Lindquist, Susan Lucas, Igor V Grigoriev, Harris Shapiro and Daniel S. Rokhsar at U.S. Department of Energy Joint Genome Institute in Walnut Creek, Patrick Ferris at the Salk Institute for Biological Studies, Aurora Nedelcu at the University of New Brunswick in Fredericton, Canada, Arman Hallmann at the University of Bielefeld, Germany, Stephen M. Miller at the University of Maryland, Baltimore, Ichiro Nishii at the Nara Women’s University in Nara-shi, Japan, Lillian K. Fritz-Laylin at the Center for Integrative Genomics, Berkeley, Oleg Simakov at the EMBL in Heidelberg, Germany, Stefan A. Rensing at the University of Freiburg, Germany, Vladimir Kapitonov and Jerzy Jurka at the Genetic Information Research Institute in Mountain View, Jeremy Schmutz at the HudsonAlpha Institute in Huntsville, Rüdiger Schmitt at the University of Regensburg, Germany and David Kirk at Washington University in St. Louis.

Looks like multicellularity was inevitable… again… and again.

More preadaptations:
Genome of Ancient Sponge Reveals Origins of First Animals, Cancer

ScienceDaily (Aug. 4, 2010) — The sponge, which was not recognized as an animal until the 19th century, is now the simplest and most ancient group of animals to have their genome sequenced.
In a paper appearing in the August 5 issue of the journal Nature, a team of researchers led by Daniel Rokhsar of the University of California, Berkeley, and the Department of Energy's Joint Genome Institute (JGI), report [b]the draft genome sequence of the sea sponge Amphimedon queenslandica and several insights the genome gives into the origins of both the first animals and cancer.[/b]

All living animals are descended from the common ancestor of sponges and humans, which lived more than 600 million years ago. A sponge-like creature may have been the first organism with more than one cell type and the ability to develop from a fertilized egg produced by the merger of sperm and egg cells.- that is, an animal.

“Our hypothesis is that multicellularity and cancer are two sides of the same coin,” said Rokhsar, program head for computational genomics at JGI and a professor of molecular and cell biology and of physics at UC Berkeley. “If you are a cell in a multicellular organism, you have to cooperate with other cells in your body, making sure that you divide when you are supposed to as part of the team. The genes that regulate this cooperation are also the ones whose disruption can cause cells to behave selfishly and grow in uncontrolled ways to the detriment of the organism.”

As part of the new analysis, the team looked in the sponge genome for more than 100 genes that have been implicated in human cancers and found about 90 percent of them. Future research will show what roles these genes play in endowing sponge cells with team spirit.

Sponges are often described as the “simplest” living animals, while humans are considered relatively “complex,” but how this differential complexity is encoded in the genome is still a major question in biology The new study shows that, while the sponge genome contains most of the gene families found in humans, the number of genes in each family has changed significantly over the past 600 million years. By analyzing which gene families were enriched or depleted in different groups of animals, the authors identified groups of gene functions that are associated with morphological complexity.

“The genome raises questions of what it means to be an animal,” said first author Mansi Srivastava, a former UC Berkeley graduate student who now is a post-doctoral associate at the Whitehead Institute for Biomedical Research in Cambridge, Mass.

"Though we think of a sponge as a simple creature whose skeleton we take to the bathtub, it has a lot of the major biochemical and developmental pathways we associate with complex functions in humans and other more complex animals," she said. “But there are certain missing components. Future studies will reveal how sponges operate as bona fide animals without those components, and how the addition of those components led to the evolution of more complex animals.”

Some of the missing components are involved in the cell cycle, the series of steps cells go through in order to divide. Among these is the enzyme family known as cyclin-dependent kinase 4/6 (CDK 4/6), which in mammals is crucial to transitioning between phases of the cell cycle. Though CDK4/6 was not found in the sponge genome, it is present in the sea anemone genome, raising the question of whether the appearance of CDK4/6 in the ancestor of “true” animals (eumetazoans) changed the animal cell cycle in a fundamental way. Inhibitors of CDK 4/6 halt the cell cycle and are used to treat breast cancer.

The authors also identified in the sponge many of the same genes that characterize all other animals: genes involved not only in cell division and growth, but also in programmed cell death; the adhesion of cells to other tissue and to one another, signaling pathways during development, recognition of self and non-self; and genes leading to the formation of different cell types.

What sponges lack, however, are a gut, muscles and neurons.

“This incredibly old ancestor possessed the same core building blocks for multicellular form and function that still sits at the heart of all living animals, including humans,” said coauthor Bernie Degnan, a professor of biology at the University of Queensland, Australia, who collected the sponge whose genome was sequenced from the Great Barrier Reef. “It now appears that the evolution of these genes not only allowed the first animals to colonize the ancient oceans, but underpinned the evolution of the full biodiversity of animals we see today.”

According to Degnan, essentially all the genomic innovations that we deem necessary for intricate modern animal life have their origins much further back in time that anyone anticipated, predating the Cambrian explosion by tens if not hundreds of millions of years.

“What marked the evolutionary origin of animals was the ability of individual cells to assume specialized properties and work together for the greater good of the entire organism. The sponge represents a window on this ancient and momentous event,” said coauthor Dr. Kenneth S. Kosik, the Harriman Professor of Neuroscience at UC Santa Barbara and co-director of the Neuroscience Research Institute.

“Remarkably, the sponge genome now reveals that, along the way toward the emergence of animals, genes for an entire network of many specialized cells evolved and laid the basis for the core gene logic of organisms that no longer functioned as single cells,” he said, “but as a cooperative community of specialized cells all geared toward the survival of a complex multi-cellular creature.”

“The beauty of having this genome is that now we can ask about all known biological processes, and go through hundreds of genes to tell definitively whether or not our common animal ancestor had them or not,” Srivastava said.

The sponge genome may also have more practical implications, according to Degnan.

“Sponges produce an amazing array of chemicals of direct interest to the pharmaceutical industry,” he said. “They also biofabricate silica fibers directly from sea water in an environmentally benign manner, which is of great interest in communications. With the genome in hand, we can decipher the methods used by these simple animals to produce materials that far exceed our current engineering and chemistry capabilities.”