User:Federico Castro M/Projects/VSFH

This project is about designing an organism that resembles the Last Universal Common Ancestor and whose construction is feasible.

Replication machinery
We have to start by:

Concivably an organism could survive in a controlled environment with a minimal genome of just 113kbp and 151 genes (Forster 2006). However, recent estimates sugest that LUCA was complex and probably had more than 600 genes (Kooning 2003).
 * Estimate the genomic size of LUCA.

Recent estimates of the minimal gene content of LUCA based on whole-genome phylogenies identified over 1000 gene families (between 1144 and 1529 when eukaryotes are included) (Ouzounis et al., 2006)


 * Check if a RNA genome can sustain such genome size.

RNA is much more error-prone than DNA due to its higher mutation rate, so that RNA molecules cannot exceed certain size (Eigen limit) without falling into replicative catastrophe (Eigen 2002). This limit is small ~30-50kb which is only enough for a dozen genes or so.

Moreover, the largest viral RNA genomes identified so far does not exceed 30kb. It is reasonable to assume that the largest modern RNA viruses are indicative of the upper size limit for an RNA world genome.

From comparative study Mushegian and Koonin concluded that LUCA lacked the genetic machinery to sustain DNA and thus it had a RNA genome with aproximately 260 genes (Mushegian and Koonin 1996). However Becerra arguments that LUCA already had some features that are coherent with a DNA genome such as large conserved proteins and a large number of genes. Moreover, he attributes the absence of DNA related machinery in Mushegian and Koonin's analysis to a secondary loss since they were using parasites for their work.
 * Did LUCA have the necesary genetic machinery to support DNA?

Harris found universal genes involved in DNA replication and repair, nontheless its number was very small (Harris 2002).

Recently, some DNA processing gene families/functions have been identified in LUCA using whole-genome phylogenetic analysis. Some of them are DNA polymerase, excinuclease ABC, DNA gyrase and topoisomerase, NADdependent DNA ligase, DNA helicases, DNA mismatch repair MutS and MutT, endonucleases, chromosome segregation SMC, methyltransferase, among others. Thus, showing that most aspects of DNA metabolism and information processing are well-represented in the minimal reconstruction of LUCA (Ouzounis et al., 2006)

The idea of a LUCA that had and maintained DNA has been supported by David Penny and Anthony Poole (://awcmee.massey.ac.nz/people/dpenny/pdf/Penny_Poole_1999.pdf Penny & Poole, 1999) argumenting that an eukaryotic genetic machinery is, actually, and ancestral characteristic.

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