Self Replicating Systems Ecoli – division and replication IL 33 Radiolara, Institut fur Leichte Flachentragwerke,1990. Prof. Joseph Jacobson MIT Media Laboratory

Goal For Next Decade: Maximize complexity per unit volume. (6 orders of magnitude left to go in complexity of engineered systems). To be useful for many applications must be able to manufacture multiple copies. Self replicating systems may be useful in attaining that goal and it represents a new discipline in engineering.

Nature holds the record in both complexity per unit volume And in the ability to carry out self replication. http://www.ncc.gmu.edu/dna/repanim.htm http://focus.hms.harvard.edu/1997/Apr18_1997/polymerase.JPG

Informationless Replication Autocatalytic Chemistry Prion Replication http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journa l/v411/n6839/full/411810a0_r.html Replicated Parts Lack Complexity

Information Bearing Replication (Non-Protein Biochemical Systems) J. Szostak, Nature,409, Jan. 2001

Information Bearing Replication (Organic Synthetic Systems) Mosley et. Al. ACS Proceedings, July 2002.

How Do We Replicate Complex Systems? Amoeba dubia 670,000,000,000 Amoeba proteus 290,000,000,000                 Homo sapiens 2,900,000,000 Human immunodeficiency virus type 1 19,750 Mycoplasma genitalium 580,000 Ans. Error Correction http://gnn.tigr.org/articles/02_01/Sizing_genomes.shtml www.nature.com/nsu/010222/images/ mgenetalium_200.jpg

Error Correction in Biological Systems Has Extremely High Fidelity but… Fault Tolerant Translation Codes (Hecht): NTN encodes 5 different nonpolar residues (Met, Leu, Ile, Val and Phe) NAN encodes 6 different polar residues (Lys, His, Glu, Gln, Asp and Asn) Local Error Correction: Ribozyme: 1:103 Error Correcting Polymerase: 1:108 fidelity DNA Repair Systems: MutS System Recombination - retrieval - post replication repair Thymine Dimer bypass. E. Coli Retrieval system - Lewin Error is cumulative.Can We Create An Organism Which Does Not Have Cumulative Error?

Yes Use Error Correcting Codes Basic Idea: M strands of N Bases Result: By carrying out a consensus vote one requires only To replicate with error below some epsilon such that the global replication error is:

Scheme for Self Excising Error Correcting Codes MutS x 1 1’ DNA Polymerase To transcribe 1’ LoxP Excision of 1 Replacement with 1’ Jacobson ‘02

Combining Error Correcting Polymerase and Error Correcting Codes One Can Replicate a Genome of Arbitrary Complexity For Above Threshold M value Jacobson ‘02