Front-loading with Homeodomains

For many years now, I have been trying to flesh out the conceptualization of front-loading evolution at the origin of life. A working hypothesis has been that the first cells (uni-cellular life forms) were front-loaded with information that would facilitate the evolution of multi-cellular life. One possible candidate for such front-loaded ‘information’ would be the homeodomain proteins. These proteins play essential roles in metazoan development and are considered part of the developmental toolkit as outlined by biologist Sean Carroll.

A few months ago, a study was published that outlines data and arguments that perfectly resonate with my front-loading views. Let’s have a look.

The study is Homeodomain proteins belong to the ancestral molecular toolkit of Eukaryotes, published by French researchers, Romain Derelle, Philippe Lopez, Herve´ Le Guyader, and Michael Manuel. It was published in the June, 2007 issue of Evolution & Development (9:212–219). Feast your eyes on the abstract:

Multicellular organization arose several times by convergence during the evolution of eukaryotes (e.g., in terrestrial plants, several lineages of “algae,” fungi, and metazoans). To reconstruct the evolutionary transitions between unicellularity and multicellularity, we need a proper understanding of the origin and diversification of regulatory molecules governing the construction of a multicellular organism in these various lineages. Homeodomain (HD) proteins offer a paradigm for studying such issues, because in multicellular eukaryotes, like animals, fungi and plants, these transcription factors are extensively used in fundamental developmental processes and are highly diversified. A number of large eukaryote lineages are exclusively unicellular, however, and it remains unclear to what extent this condition reflects their primitive lack of “good building blocks” such as the HD proteins. Taking advantage from the recent burst of sequence data from a wide variety of eukaryote taxa, we show here that HD-containing transcription factors were already existing and diversified (in at least two main classes) in the last common eukaryote ancestor. Although the family was retained and independently expanded in the multicellular taxa, it was lost in several lineages of unicellular parasites or intracellular symbionts. Our findings are consistent with the idea that the common ancestor of eukaryotes was complex in molecular terms, and already possessed many of the regulatory molecules, which later favored the multiple convergent acquisition of multicellularity.

Sound familiar?

Let’s look more closely. The researchers found that homeodomain proteins “are present in all eukaryotic lineages containing multicellular organisms, and absent in exclusively unicellular lineages.” Thus, we have a good candidate for front-loading, as this protein is not essential to uni-cellular life, but does appear essential for multi-cellular organisms.

After conducting their own phylogenetic analysis, the researchers conclude:

The results of character optimization (Fig. 1) show that, instead of being a derived character of ‘‘higher’’ eukaryotes lineages enriched for multicellularity, the HD existed in the last common ancestor of all living eukaryotes. Although the HD occurs in all lineages containing multicellular organisms (animals, fungi, plants, amoebozoans, and heterokonts), this is nothing more than the retention of a eukaryotic plesiomorphy.

They also find that the last eukaryotic ancestor contained at least two specialized versions of the HD:

Thus our results extend the subdivision of HDs between TALE and non-TALE to the whole eukaryotic domain of life. Because both the groups include genes from metazoans, plants, fungi, amoebozoans, heterokonts, and Trichomonas, we conclude that the common ancestor of eukaryotes possessed at least these two distinct types of HDs.

And then note an interesting pattern:

All investigated eukaryote taxa possess either both groups of HDs or no HD at all, which we consider an intriguing observation, because after duplication, one duplicate is commonly lost in some branches of the phylogenetic tree (Force et al. 1999). Although this pattern may have occurred by chance, it may instead result from evolutionary forces acting on the genome for conservation of both of these functional categories of HDs. Possibly, they complement for the function of the ancestral HD (before the duplication)…..Relaxing the constraint, under conditions where these functions are not needed, may result in the loss of both HD categories, as observed for example in apicomplexans and kinetoplastids.

They then reach a conclusion that should be quite familiar to those who have followed my own speculations on the internet over the years:

The pattern of HD evolution recovered in this study is consistent with the view that ‘‘Ur-eukaryota’’ was a complex organism, from a molecular point of view (Forterre and Philippe 1999; Bapteste and Gribaldo 2003; Roy and Gilbert 2005), in contrast with more traditional conceptions assuming a progressive evolution toward increased complexity. Independent reduction from a complex ancestral genome is currently recognized as a major theme in eukaryote evolution (Bapteste and Gribaldo 2003; Kurland et al. 2006). As a corollary of ancestral molecular complexity, Ur-eukaryota probably possessed many of the good building blocks, which were subsequently recruited, by convergence in several lineages, to perform the functions required for development of multicellular organisms. In other terms, we suggest that the eukaryotes as a whole are preadapted for multicellularity, which only means that the ancestral complexity of the eukaryote genome and cell biology facilitated multiple acquisitions of multicellularity. This does not imply, of course, that increased complexity is a necessary outcome of eukaryote evolution.

In essence, this is the very type of result I have been predicting for front-loading – “eukaryotes as a whole are preadapted for multicellularity.”

The authors then turn to the next interesting question:

The independent diversification of HDs in the various multicellular lineages, as well as their crucial developmental role in these phylogenetically distant organisms, despite convergent acquisition of multicellularity, raise the fascinating question of the function of HD-containing transcription factors in the (unicellular) common ancestor of eukaryotes. We lay the bet that HD proteins were not primitively involved in domestic cellular regulations, but rather in higher order processes, e.g., communication between individual cells, or cell modifications along the life cycle, as already suggested by data on unicellular fungi (Johnson 1995).

If their bet is won, what we have is the last common ancestor of eukaryotes as a complex and sophisticated entity front-loaded to spawn multi-cellular life.

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