2. 1 GEK1530 Frederick H. Willeboordse frederik@chaos.nus.edu.sg Nature’s Monte Carlo Bakery: The Story of Life as a Complex System

3. 2 DNA as a Hard Disk – The Cell as a Computer Lecture 5 When putting a cell and a computer side-by-side, which elements correspond to each other? = ? = ?

4. GEK1530 3 Today’s Lecture Hardware Hard Disk Software The Structure of a Computer The Structure of a Cell Cellular Constituents DNA Information The Story It is clear that cells often fulfill very specific functions. Indeed, one could argue that cells computer in the general sense of the word. Does this mean that there are parallels between cells and computers? In this lecture we compare the key components of both cells and computers and ask: Can DNA be considered a hard disk?

5. GEK1530 4 The Structure of a Computer The key components of a computer are: Microprocessor Memory Hard Disk Input Devices like a Mouse and a Keyboard Output Devices like a Monitor Motherboard Power Supply Casing IBM z900

6. GEK1530 5 Micro- processor North- bridge South- Bridge Graphics (AGP) Hard Disk Network PCI Bios Memory Keyboard Mouse Other I/O The Structure of a Computer

7. GEK1530 6 Key Components - Computer The Microprocessor contains the rules (built in by design) and evaluates them. In this sense it is somewhat similar to a ‘brain’. It obtains the necessary information so that it can apply the rules from memory. Though very different in computational prowess, all commercial microprocessors follow the same basic design thus far. It is often called the von Neumann architecture. The world’s first microprocessor. The Intel 4004. The Alpha 21164 chip from 1997.

8. GEK1530 7 There are various types of memory in a computer but mostly when stated like this one refers to RAM (Random Access Memory). This is a temporary memory that holds information (for the microprocessor e.g. to apply its rules on). 128MB PC133 Memory Modules Key Components - Computer

9. GEK1530 8 Conceptually, it is not necessary to distinguish between RAM and hard disk type of memory but practically having RAM leads to great speed increases. The hard disk is a permanent type of memory that stores information. It is called a hard disk because physically the information is stored on a ‘hard disk’. Maxtor 80G Hard Disk Key Components - Computer

10. GEK1530 9 The keyboard and the mouse are the most common on personal computers but there are many other possibilities (temperature sensors, heat sensors, pressure sensors – good for robots, decoded antenna signals – mobile communicators, etc). Of course one needs to be able to supply information hence we need some sort of input devices. Key Components - Computer

11. GEK1530 10 On a personal computer, the monitor is the most common output device and the component that translates output information for actual display on a screen (be that digital or analog) is called a graphics chip (which often sits on a graphics card). A computer wouldn’t be of much use if it were a black hole. Hence besides input devices, it will also need output devices. Radeon 7000 Dell P991 Key Components - Computer

12. GEK1530 11 The mainboard connects (directly or indirectly through cables) the components of the computer. Asus Pentium 4 mainboard Key Components - Computer

13. GEK1530 12 The Power Supply converts what comes from the wall plug into something suitable for the computer’s components. Key Components - Computer

14. GEK1530 13 Casing, a nice package to make sure the whole thing stays together. LianLi P61 And the fabulous features advertised on the box Key Components - Computer

15. GEK1530 14 The hard disk stores what appears to be a rather complicated program and the computer then evaluates the built-in rules according to supplied information. The very least e.g. it needs the ‘switch-on’ or start signal as external input. Even though a program is very complicated when considered as a whole, it can be broken down into smaller units transversing many levels until the final binary representation. The real function: To keep us occupied! Key Components - Computer

16. GEK1530 15 The Structure of a Cell The key components of a cell are: Endoplasmic Reticulum & Ribosomes mRNA DNA (Macro-) Molecules Golgi apparatus Filaments Mitochondria Cell Membrane

17. GEK1530 16 A Typical Bacterium Cell The Structure of a Cell Prokaryotic Cell

18. GEK1530 17 Typical Animal Cell The Structure of a Cell Eukaryotic Cell

19. GEK1530 18 Typical Plant Cell The Structure of a Cell

20. GEK1530 19 Deoxyribonucleic acid, or DNA in short is where the genes reside. From: http://www.bmb.psu.edu/tan/http://www.bmb.psu.edu/tan/ Key Components - Cell

21. GEK1530 20 Messenger ribonucleic acid, or in short mRNA transports instructions for protein synthesis from the nucleus to the protein synthesizing ribosomes. From: Biological Science 6 th Ed., Gould & Keeton p. 225 Key Components - Cell

22. GEK1530 21 Ribosomes ( ) From: http://www.rcsb.org/pdb/molecules/pdb10_1.htmlhttp://www.rcsb.org/pdb/molecules/pdb10_1.html Ribosomes are composed of two subunits that are long strands of RNA, shown here in orange and yellow, dotted with protein chains, shown in blue. When synthesizing a new protein, the two subunits lock together with a messenger RNA trapped in the space between. The ribosome then walks down the messenger RNA three nucleotides at a time, building a new protein piece-by-piece. Key Components - Cell

23. GEK1530 22 Synthesis of membrane phospholipids and packaging of proteins for transport occurs in the Endoplasmic Reticulum. It is located just outside of the nucleus. Many ribosomes are attached to the so-called rough endoplasmic reticulum. Key Components - Cell

24. GEK1530 23 Generally, Macro- molecules like Proteins have specific functions in cells. The picture on the right e.g. shows hemoglobin, the molecule responsible for transporting oxygen. From: Biological Science 6 th Ed., Gould & Keeton p. 65 Key Components - Cell

25. GEK1530 24 The Golgi ( ) apparatus stores, modifies and packages secretory products of the cell. From: Biological Science 6 th Ed., Gould & Keeton p. 129 Key Components - Cell

26. GEK1530 25 Filaments ( ) provide structural support and pathways along which molecules can be transported. From: Biological Science 6 th Ed., Gould & Keeton p. 122 Key Components - Cell

27. GEK1530 26 The Mitochondria ( ) are the power plants of the cell. From: The Cell 4 th Ed., Alberts et al p.31 Key Components - Cell The primary function of a mitochondrion is the manufacturing of Adenosine Triphosphate (ATP) which is used as a ‘fuel’ (energy source in other parts of the cell) Mitochondria are organelles which may have been independent organisms early during evolution. They have their own DNA.

28. GEK1530 27 Naturally, a cell needs to somehow isolate itself from its environment. This is achieved through the existence of a Cell Membrane. The cell membrane is not a impermeable wall, however, and plays an essential role by selectively letting atoms or molecules in or out. From: Biological Science 6 th Ed., Gould & Keeton p. 99 Key Components - Cell

29. GEK1530 28 Functioning of a Cell In many senses, cells can be considered protein factories where instructions stored in genes is executed depending on the cells state.

30. GEK1530 29 From Oxford English Dictionary: 1970 Scientific American Oct.19: “The human genome consists of perhaps as many as 10 million genes.” In this context it is particularly noteworthy that: In fact: The human genome has only about 30 thousand genes! This is a remarkably small number. DNA as a ‘hard disk’

31. GEK1530 30 Complementary to considering DNA as a hard disk is the idea that evolution is a process of natural genetic engineering. It should be stressed that this is a complex systems view and does not require ‘intelligent’ as in ‘divine’ design. The genetic engineering properties are simply consequences of (by natural selection) surviving systems designs. The most simple ones reflecting nothing but the chemical properties of its constituents (e.g. bi-layers made of phospholipids). DNA as a ‘hard disk’

32. GEK1530 31 A genome consists of many parts. The most commonly studied parts (due to their perceived relevance for medical applications) are the so-called coding regions that determine the proteins that can be synthesized. The other regions are often referred to as junk! Is that a reasonable assessment though? In fact there are many classes genomic information: ? ? DNA as a ‘hard disk’

33. GEK1530 32 start and stop sites for transcription control signals for e.g. level of expression Signals for chromatin remodeling Signals for DNA replication Signals for DNA repair It is very important to realize that the genome only functions in response to its environment. DNA, by itself, doesn’t do anything, it is inert. The information stored in the DNA is only activated due to its interaction with the rest of the cell (this should be obvious considering e.g. cell differentiation). DNA as a ‘hard disk’

34. GEK1530 33 A concrete example: The lac operon OED: operon: A unit of co-ordinated gene activity which is believed to account for inducible and repressible enzymes in bacteria and hence for the regulation of protein synthesis, and is usu. conceived as a linear sequence of genetic material comprising an operator, a promoter, and one or more structural genes. The lac operon encodes the capacity for lactose utilization in E. coli. 1947 lac The operon is a small section of the genome What is interesting, though, is that E. coli can distinguish glucose and lactose. If available, they’ll first consume the glucose. Hence there must be some kind of mechanism to regulate this. DNA as a ‘hard disk’

35. GEK1530 34 1961 And of course it wouldn’t end here: Y Z O A I Structural genes for encoding the proteins of lactose transport and metabolism An operator: here, the site where the repressor binds to stop lacZYA (note this is not a gene!) Regulator gene that encodes a repressor protein It’s not that simple! Y Z O A I O2 O3 CRP P O Co-operative binding site for the repressor together with O3 The repressor binding site A promoter site Binding site for the transcription factor that mediates glucose control Co-operative binding site for the repressor together with O2 1990 DNA as a ‘hard disk’

36. GEK1530 35 DNA as a ‘hard disk’

37. GEK1530 36 Overall, the cell performs the following computation: IFlactose present AND glucose not present ANDcell can actually synthesize active LacZ and LacY THENtranscribe lacZYA from lacP It is important to note that the computation involves many molecules and compartments of the cell, not just DNA. E.g. the availability of lactose needs to be signaled to it. DNA as a ‘hard disk’

38. GEK1530 37 Computer and Cell compared The key components side by side Microprocessor Memory Hard Disk Input Devices Output Devices Motherboard Power Supply Casing EPR & Ribosomes mRNA DNA (Macro-) Molecules Golgi apparatus Filaments Mitochondria Cell Membrane ? ? ? ? ? ? ? ?

39. GEK1530 38 Wrapping up Key Points of the Day Give it some thought References Is life a computing? In a certain way a cell is a lot like a computer. Does a computer need chaos to operate? No! Perhaps adding using chaos gives cells a distinctive advantage. At least not at this moment. In a computer, hopefully nowhere! In a cell, perhaps everywhere! Where is “the Chaos”?