A Reconciliation of Faith and Science. Jacek Błażewicz Instytut Informatyki Politechnika Poznańska & Instytut Chemii Bioorganicznej Polska Akademia Nauk Molecular biology Chemical foundations of life Information coded in chemical molecules Computational biology Computing Science Molecular Biology Problems Methods Problems Methods Operations Research One dimensional structures 1. Reading DNA chains 2. Understanding an information contained in DNA sequence alignment finding motifs in sequences assigning functions to subsequences (or motifs) Levels Sequencing up to 700 (150) nucleotides combinatorial exact methods Assembling up to 1000000 (100000000) nucleotides heuristics Mapping greater than 1000000 nucleotides search in data bases Genetic linkage map Chromosome (works on 107-108 bp range) Assembling Clones (works on 105-106 bp range) Sequencing (works on 103-104 bp range) CGGACACCGACGTCATTCTCATGTGCTTCTCGGCACA The different scales at which the human genome is studied Hybridization Experiment Hybridization reaction DNA chip TCCACTG... Many labeled copies of an original sequence Reading results Fluorescence image of the chip . . . . . . . spectrum Spectrum – a set of oligonucleotides complementary to fragments of original sequence A hybridization reaction between a probe of known sequence (l-mer) and an unknown sequence (n-mer): n-mer - . . . A A C T A G A C C T . . . l-mer - GAT CTA A sequence complementary to the probe exists in the target DNA sequencing without errors The original sequence: AACTAGACCT Spectrum = {AAC,ACT,CTA,TAG,AGA,GAC,ACC,CCT} (Two possible solutions: AACTAGACCT, AACCTAGACT) Lysov (1988) A graph is based on l-mers (graph H) AAC ACT CTA CCT TAG ACC GAC AGA Finding a Hamiltonian path – NP-hard The above class of directed labeled graphs – DNA graphs. Characterization and recognition of these graphs and finding conditions for which the above transformation is possible. J.Blazewicz, A.Hertz, D.Kobler, D.de Werra, On some properties of DNA graphs, Discrete Applied Math., 1999. DNA sequencing in the presence of positive and negative errors Formulation as a variant of Selective Travelling Salesman Problem: Given a complete digraph G=(V,A), V=spectrum, with all vertex profits equal to 1 and arc costs equal to values of overlaps between vertex labels, find a path of maximal total profit and total cost not greater than n-l. [J.Blazewicz, P.Formanowicz, M.Kasprzak, W.T.Markiewicz, J.Węglarz, Journal of the Computational Biology, 1999] CTT CTT TAC GCG ACG ACT CTA cost = 1, e.g. T(AC)T cost = 2, e.g. AC(T)AC TAC GCG ACG ACT CTA Two optimal solutions How complicated is human genome? How big is the information it contains? DNA recognition Human genome 3 109 pairs of bases 3% nucleotides coding an information Die Bibel: Altes und Neues Testament. Einheitsübersetzung Verlag Herder, Freiburg, 1999 (ca 1500 pp) Die Bibel: Altes und Neues Testament. Einheitsübersetzung Verlag Herder, Freiburg, 1999 (ca 1500 pp) Human genome 1 cell bacteria Some flies 1000 books (valid information 90 books) 7 books 1600 books The theory of the origin of the Universe There was a definite beginning in which all its matter and energy were concentrated at one point, around 13.7 billion years ago An opposition to the concept of an eternal universe, infinite in age and constant in its general appearance Proposed in 1927 by Georges Lemaître – a Belgian Roman Catholic priest, professor of physics and astronomer BIG BANG Evidence Redshift of galaxies resulting from universe expansion (Doppler effect) Cosmic microwave background Abundance of light elements (production of nuclei other than those of H-1) Large scale distribution and apparent evolution of galaxies The result of retrodiction, based on remarks of the expanding universe Future predictions depend on dark matter and dark energy Big Crunch Big Freeze Heat Death Flatness hypothesis etc. Big Bang - timeline 0 – 10-43 s Planck epoch Extremely hot and dense universe starts to expand about 13.7 bilion years ago. 10–43 - 10–36 s Grand unification epoch The universe expands and cools down. Gravitation separates from electromagnetism .and nuclear forces 10–36 - 10–12 s Electroweak epoch Lower temperature allows for separation of strong force from the electroweak force. W, Z and Higgs bosons are created. 10–36 - 10–32 s Inflationary epoch The universe is flattened and dominated by radioation. The seeds of structure formation are laid down: quarks, electrons and neutrinos form. 10–12 - 10–6 s 10–6 - 1 s 1 -10 s Quark epoch The fundamental interactions of gravitation, electromagnetism, the strong interaction and the weak interaction have taken their present forms Hadron epoch Due to lower temperature baryons such as protons and neutrons can form. Lepton epoch Leptons are no longer created and are eliminated in annihilation reactions Big Bang – timeline (2) 10 s - 380 000 years 3 -20 min 70 000 years Photon epoch The universe is dominated by photons, interacting frequently with charged protons, electrons and (eventually) nuclei. Protons (hydrogen ions) and neutrons begin to combine into atomic nuclei in the process of nuclear fusion. There is about three times more hydrogen than helium-4 (by mass) and only trace quantities of other nuclei. Cold dark matter dominates; densing of dense regions of the universe. 377 000 years Forming electrically neutral atoms by capturing electrons by ions. Photons can travel free, the universe becomes transparent. 150 mln - 1 bln years Reionization Most of the universe is composed of plasma, first stars and quasars are formed, then galaxies and groups. 8 bln years 8.5 bln years Solar system Our galaxy is formed roughly 5 bln years ago. Earth The age of the Earth has been determined to 4.54 billion years Life on Earth - timeline 4.54 - 3.8 bln years ago 3.5 bya 3 bya 3 - 2.4 bya 2 bya Formation of Earth Heavy bombardments by meteorites, asteroids and commets. Volcanism resulting from the large heat flow and geothermal gradient. Oceans and simple atmosphere is created, then tectonic plates and first continents. Cooling, first life on Earth Beginning of the evolution of primordial life in an atmosphere without oxygen and an ozone layer Formation of the first known continent, Ur. Proliferation of cyanobacteria. – the evolution of photosynthesis, which leads to production of oxygen as byproduct led to the Great Oxidation Event: the Earth's atmosphere got oxygen. Evolution of cells with nuclei 1.6 bya First blue-green algae. Natural evolution 1.3 bya First plants. Charles Darwin 630-850 mya 670 mya 600-500 mya The Cryogenian Period - the worst ice age in the Earth's history. First animals. Cambrian explosion – a sharp increase in the diversity and number of complex animals 440 mya The Ordovician-Silurian extinction – most marine species died out. 395 mya First insects on land. Life on Earth – timeline (2) 365 mya The Late Devonian extinction. 70% of marine species died out . First amphibians, trees. 313 mya First reptiles. 250 mya The Permian-Triassic extinction. 90% of all species died out. Formation of the supercontinent Pangaea 235 mya First dinosaurs, flowers. 150 mya First birds 114 mya First modern mammals. World begins to cool. 67 mya Cretaceous-Tertiary extinction caused by asteroid hit in Mexico. End of dinosaurs. 50% of all species died out. Intensification of world cooling trend. 21 mya Apes split off from other monkeys. 5 mya Humans split off from other apes (gorillas and chimpanzees). 3.9 mya First known Australopithecus afarensis. 2.5 mya First Homo habilis. 1.9 mya First Homo erectus. 620-380 tya Interglacias period 350 tya First Homo neanderthalensis. 250 tya First Homo sapiens. Clock of the history of life What is life – some definitions Cosmology point of view • Living systems self-assemble against nature’s tendency toward disorder, or entropy (Erwin Schrödinger) • Life processes low-entropy solar energy changing it into an order, releasing disorder (heat) into the outer space (Michał Heller) Biologically inspired • Living systems are characterized by selfprocessed metabolism (acquiring energy) and ability of autoreplication (Andrzej Legocki) • Life is a compound set of chemical reactions and electron processes in a semi-conductive environment of proteins (Włodzimierz Sedlak) Genomic perspective • Life is defined by a minimal set of important genes (Jan Barciszewski) • Complex biochemical structures may be considered as alive if they are capable of evolution via natural selection (Jan Kozłowski) • Life is a self-sustaining chemical system capable of Darwinian evolution (Gerald Joyce’s definition adopted by NASA) Cybernetic point of view • Life is a network of feedback mechanisms (Bernard Korzeniewski) Computer science point of view • Life is a system carrying and processing information, capable of replicating itself without a help of other systems that do not belong to the same type. Biological primer Protein synthesis (or gene expression): a two stage process of information transfer involving many smaller discrete steps and many molecular machines (genetic code is a set of correspondences between specific groups of bases and individual amino acids): • Transcription • Translation Transcription • • • S. C. Meyer, Signature in the Cell, HarperOne, NY, 2009. RNA polymerase makes an identical copy of the DNA in a RNA format. The resulting single-stranded RNA copy moves from the chromosomes to the ribosome to begin translation. RNA polymerase is a complex protein machine of great specificity. Transcription • S. C. Meyer, Signature in the Cell, HarperOne, NY, 2009. • The structure of the RNA polymerases reflects the complexity of their activities in RNA transcription (Stephen Wolfe). RNA polymerase alone does not ensure accurate transcription. Even in prokaryotic organisms, many separate proteins are necessary to facilitate and regulate transcription. Translation • • S. C. Meyer, Signature in the Cell, HarperOne, NY, 2009. The process of translating information from the fourcharacter alphabets of DNA and RNA into the twentycharacter amino-acid alphabet. Even in the simplest prokaryotic cells, the proces of translation utilizes many dozens of separate proteins each one of which is produced during translation. Is this scheme universal for all the organisms? What about the genetic code? In human cells, the codon UGA codes for „stop”, meaning the end of an ORF. In Mycoplasma, the codon UGA codes for the amino acid tryptophan. Human and Mycoplasma cells do not read their DNA in the same way. http://www.ncbi.nlm.nih.gov/Taxonomy/taxonomyhome.html/index.cgi?chapter=cgencodes Notion of the information Shannon linked the concepts of information and uncertainty (measured by probability). The amount of information conveyed (and the amount of uncertainty reduced) in a series of symbols is inversely proportional to the probability of a particular event or symbol occurring. Ex: An outcome of rolling a six-sided die is more improbable than an outcome of flipping a coin, thus, it conveys more information. Shannon’s theory implies also that information increases as a sequence of characters grows but it cannot distinguish functional or message-bearing sequences from random or useless ones. Biological sequences carry not only potential (Shannon’s) complexity but also a functional one (called specificity). Ex: Proteins display specificity in the arrangement of aminoacids and in shape. S. C. Meyer, Signature in the Cell, HarperOne, NY, 2009. Hypotheses of the beginning Chance alone What is chance? Random process Chance hypothesis can be eliminated when a series of events occurs that deviates too greatly from an expected statistical distribution of the events in question. What is the probability of generating by chance a functional protein of length 150 aa? (Sauer, 1990; Axe 2004). 1. Peptide bonds vs non-peptide ones S. C. Meyer, Signature in the Cell, HarperOne, NY, 2009. Pr{𝑝𝑒𝑝𝑡} = 1 149 1 45 ( ) ≈ (10) 2 2. Left-handed (L-form) vs right-handed (D-form) optical isomers Two optical isomers of the same amino acid. S. C. Meyer, Signature in the Cell, HarperOne, NY, 2009. Pr{𝐿 − 𝑓𝑜𝑟𝑚} = 1 149 1 45 ( ) ≈ (10) 2 Thus, probability of building 150 aa chain at random is: Pr{150 𝑎𝑎 𝑐ℎ𝑎𝑖𝑛} ≈ 1 45 ( ) 10 * 1 45 ( ) 10 = 1 90 ( ) 10 3. But if one required a particular 150 aa chain then: Pr{𝑝𝑎𝑟𝑡𝑖𝑐𝑢𝑙𝑎𝑟 𝑎𝑎 𝑐𝑜𝑚𝑏. } = 1 150 1 195 ( ) ≈ (10) 20 3’. On the other hand, because of existing aa variance in protein chains, it may be shown using „casette mutagenesis” technique (Sauer, 1990; Axe 2004), that Pr{𝑝𝑟𝑜𝑑𝑢𝑐𝑖𝑛𝑔 𝑎𝑛𝑦 𝑓𝑢𝑛𝑐𝑡𝑖𝑜𝑛𝑎𝑙 150 𝑎𝑎 protein from aminoacids} ≈ 1 74 ( ) 10 Summing up: The probability that a 150-amino-acid compound assembled by random interactions in a prebiotic soup would be a functional protein (event X) can be estimated as: Pr{𝑋} ≈ 1 74 ( ) 10 * 1 45 ( ) 10 * 1 45 ( ) 10 ≈ 1 164 ( ) 10 But are there enough probabilistic resources in the universe? • How many chances had particles to interact since the big-bang? (Borel, van de Sande, Dembski) There are: 1. 1080 elementary particles in the observable universe 2. 1043 state changes of particles/s (inverse of the Planck time) 3. 1016 s since the big bang • Summing up we have: 1080 * 1043 * 1016 = 10139 observable events in the universe, which is equivalent to the measure of the probabilistic resources of the entire observable universe. This is much too small for the required probability of 1 164 ( ) of getting functionally fit protein of 10 length 150 aa. (Odds of producing the minimum cell equipped with the desired set of proteins 1 41000 ≤ (10) .) Conclusion Chance alone hypothesis is very improbable! Lawlike processes (determination) II. Self-Organization and Biochemical Predestination Self-organization refers (in physics) to a spontaneous increase in the order of the system due to some natural process, force or law (e.g. a vortex forms in a bathub as the water swirls down). S-O theories of the origin of life try to attribute the organization in living things to physical or chemical forces or processes (laws of nature). Biochemical Predestination (Kenyon and Steinman) Simple monomers (amino-acids, bases and sugars) arose from simpler atmospheric gases and energy. Polymers (proteins and DNA) arose from monomers. Primitive membranes formed around these polymers. Primitive metabolism emerged inside these membranes as various polymers interacted chemically with one another. All that was driven by forces of chemical necessity, which were also responsible for the origins of life. This protein-first model could not explain the origins of DNA information. It fails to find any significant chemical interaction between the codons on mRNA and the amino-acids on the acceptor arm of tRNA to which the codon corresponds. The triplet at the 3’ acceptor end of tRNA (ACC) is the same for all 20 tRNA molecules. S. C. Meyer, Signature in the Cell, HarperOne, NY, 2009. In fact, the codon - aa relationship (defining genetic code) is established and mediated by the catalytic action of some 20 separate proteins (aminoacyl-tRNA synthetases) – highly specific biopolymers (origin ?). Moreover, the discovery of seventeen variant genetic codes (in different microorganisms) indicates that chemical properties of relevant monomers allow for several „codes”, thus nothing here is biochemically predestined. III. Self-organization via external forces In Self-Organization in Nonequilibrium Systems Prigogine and Nicolis suggested that energy flowing into primitive living systems might have played a role in the origin of biological organization. But what needs explaining here is not order (in the sense of a symmetrical or repeating pattern), but information, the kind of specified digital information found in DNA (as well as in computer software). Here this approach fails to explain the issue. Kauffman in The Origins of Order: Self-Organization and Selection in Evolution presents a new model – metabolism first. Here, a self-reproducing metabolic system might emerge directly from a set of „low-specificity” catalytic peptides and RNA molecules in a prebiotic soup. In other words this is „a set of catalytic polymers in which no single molecule reproduces itself but the system as a whole does.” Again fails to explain the orgins of specified complexity of biological molecules. Necessity alone fails to explain the origins of life, but what about chance and necessity together? Hypotheses of the beginning copyright Scripps Inst. Interactions between Faith and Science Creationism (in its pure form, i.e. verbatim understanding of the biblical description of the creation of the world) Faith dominates Science Atheism and Agnosticism Science dominates Faith The ways to reconcile Faith with Science Intelligent Design (Ph.Johnson, M.Behe, W.Dembski, S.Meyer) Evolution is fundamentally flawed, since it cannot account for the intricate (irreducible) complexity of nature, thus, an Intelligent Designer had to step in (several times) to provide the necessary components during the course of evolution. However, the existing gaps in evolution that ID wanted to fill by God are now filled by the advances in science. Biologos (F.Collins) Based on Theistic Evolution (A.Gray, T.Dobzhansky) God, who is not limited in space or time, created the universe and established natural laws that govern it. God chose also the mechanism of evolution to create microbes, plants and animals, as well as men who would have intelligence, a knowledge of right and wrong, free will, and a desire to seek fellowship with Him (F.Collins). www.biologos.org Conclusion • The world needs scientists, but a scientific outlook becomes dangerously narrow if it ignores the religious or ethical dimension of life, just as religion becomes narrow if it rejects the legitimate contribution of science to our understanding of the world. Pope Benedict XVI (cited by HE Vincent Nichols)