Nudging Multicellularity into Existence

As we have seen, the bacterial and archaeal RNA polyermase (RNAP) differ in complexity. Despite the fact that the cell plan of both life forms is small, relatively simple, and streamlined, the RNAPs differ remarkably in terms of complexity, where the bacterial version is built from four parts, while the archaeal version is built from 11 parts. The archaeal version has homologs of the four bacterial components needed to carry out the core process of transcription, meaning the remaining parts are “bells and whistles”

As far as I have been able to determine, no one has thought to ask why the archaeal RNAP is so much more needlessly complex than the bacterial version. I would expect the non-teleological perspective would “explain” this disparity by insisting that there are many ways to transcribe DNA into RNA and these two RNAPs would merely reflect the many roads to Rome. But that is not a very satisfying speculation. So let me be the first to ask the question and the first to propose an answer.

From the hypothesis of front-loading, allow me to formulate a testable hypothesis – the “bells and whistles” of the archaeal RNAP – Rbp 4, 5, 7, 10, 11, and 12 – will play crucial roles in the emergence of a) the eukaryotic cell and/or b) complex, metazoan life

If we begin our analysis by focusing on Rbp4 and 7, which function together as a dimer, we have already seen some clues to support this hypothesis. First, Rnp4 and probably 7 are not needed in order for archaebacteria or single-celled yeast cells to survive, but are essential for the survival of multicellular fungi. Second, Rnp4/7 appear to be preadapted to facilitate the emergence of the complex eukaryotic cell plan given they not only function in transcription, but also moonlight to control RNA decay outside of the nucleus. Let’s now add some more clues.

It turns out that Rbp4 is essential for embryological development in flies. A recent experiment determined that RNA levels of Rbp4 were high early in development and then decreased later in development. And when the Rpb4 gene is removed by genetic manipulation, death occurs during the early stages of larval development [1]. So while Rpb4 is not needed for archaebacterial or single-celled eukaryotic survival, it is needed for embryological development.

If we go back to baker’s yeast, Rpb4 and 7 can function as a switch to help cells “decide” how to proceed under the stress of starvation. The cell essentially has two choices – to activate a program that will generate spores (go dormant and wait for things to improve)or to activate a program that will generate pseudohyphae which, as you can see from “b” in the figure below, are multicellular filaments/”feelers” that spread out to improve the odds of nutrient retrieval.

According to the study that documented this switch behavior:

The Rpb4/7 subcomplex of RNA polymerase II in Saccharomyces cerevisiae is known to play an important role in stress response and stress survival. These two proteins perform overlapping functions ensuring an appropriate cellular response through transcriptional regulation of gene expression. Rpb4 and Rpb7 also perform many cellular functions either together or independent of one another. Here, we show that Rpb4 and Rpb7 differently affect during the nutritional starvation response pathways of sporulation and pseudohyphae formation. Rpb4 enhances the cells’ proficiency to sporulate but suppresses pseudohyphal growth. On the other hand, Rpb7 promotes pseudohyphal growth and suppresses sporulation in a dose-dependent manner. We present a model whereby the stoichiometry of Rpb4 and Rpb7 and their relative levels in the cell play a switch like role in establishing either sporulation or pseudohyphal gene expression. [2]

So two of the archaeal ‘bells and whistles’ are behaving as a switch, where one option is to proceed along lines of developing a simple multicellular state. But it gets better.

Another study [3] looked at fission yeast:

And found that Rpb4 controls the expression levels of genes involved in cell separation after mitosis:

To learn more about the roles of Rpb4, we expressed the rpb4 gene under the control of regulatable promoters of different strength in fission yeast. We demonstrate that below a critical level of transcription, Rpb4 affects cellular growth proportional to its expression levels: cells expressing lower levels of rpb4 grew slower compared to cells expressing higher levels. Lowered rpb4 expression did not affect cell survival under several stress conditions, but it caused specific defects in cell separation similar to sep mutants. Microarray analysis revealed that lowered rpb4 expression causes a global reduction in gene expression, but the transcript levels of a distinct subset of genes were particularly responsive to changes in rpb4 expression.

They also noted:

Fission yeast cells grown under low expression of rpb4 were elongated and showed defects in cell separation as indicated by the accumulation of division septa, some of them highly aberrant (Fig. 3).

And interpret this as follows:

in abundant nutrients, global transcription is efficient and growth is best as single cells, while in limiting nutrients, global transcription and cell separation are compromised, and cells grow as multicellular pseudohyphae, which may allow a more efficient grazing for new nutrients as growth is directed.

So what began as a needless component of the archaeal RNAP has taken on a role involved in the generation of multicellular structures. In fact, with the failure to complete cell separation, the whole system seems poised to generate true hyphae or even a syncytium (which plays a key role in early development in flies). As far as Rpb4 and 7 go, the data do indeed support my front-loading hypothesis. These two components can be viewed as part of a choice architecture that would eventually nudge a multicellular state into existence.

—–

1. Pankotai T, Ujfaludi Z, Vámos E, Suri K, Boros IM. 2009. The dissociable RPB4 subunit of RNA Pol II has vital functions in Drosophila. Mol Genet Genomics. 283(1):89-97.

2. Singh SR, Pillai B, Balakrishnan B, Naorem A, Sadhale PP. 2007.
Relative levels of RNA polII subunits differentially affect starvation response in budding yeast. Biochem Biophys Res Commun. 356(1):266-72.

3. Sharma N, Marguerat S, Mehta S, Watt S, Bähler J. 2006. The fission yeast Rpb4 subunit of RNA polymerase II plays a specialized role in cell separation. Mol Genet Genomics. 276(6):545-54.

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