Biology Primer Rinku Saha Biomedical Informatics Team UAMS

1. Biology Primer Rinku Saha Biomedical Informatics Team UAMS

2. The Cell Cell is the basic unit of life in all biological organisms on earthl. A cell is basically a watery solution of certain molecules, surrounded by a lipid (fat) membrane. Typical sizes of cells range from 1 m (bacteria) to 100 m (plant cells). There are estimated about 6x1013 cells in a human body, of about 320 different types. For instance there are several types of skin cells, muscle cells, brain cells (neurons), among many others. There are two types of organisms - eukaryotes and prokaryotes.Bacteria belong to the prokaryotes. However, most organisms which we can see, such as trees, grass, flowers, weeds, worms, flies, mice, cats, dogs, humans, mushrooms and yeast are eukaryotes. There are four basic types of molecules involved in life:Small molecules(ex:amino acids),DNA,RNA,Protein .Proteins, DNA and RNA are known collectively as biological macromolecules. The study of structure, function, and makeup of biologically important molecules is called molecular biology.

3. Molecular Biology Developments in modern biology have their roots in the interdisciplinary work of scientists from many fields. This was a crucial element in the breaking of the code of life; Max Delbrück, Francis Crick and Maurice Wilkins all had backgrounds in physics. In fact, it was the physicist Erwin Schrödinger (ever heard about Schrödinger's cat ?), who in "What is life" was the first to suggest that the "gene" could be viewed as an information carrier whose physical structure corresponds to a succession of elements in a hereditary code script. This later turned out to be the DNA, one of the two types of molecules "on which life is built". This work inspired James Watson and Francis Crick in 1953 to elucidate the structure of DNA - the ABC of all known living matter. To cut a long story short over the next years many people pieced the puzzle together: The building blocks of life are the 20 amino acids that make up proteins; DNA contains the blueprints for these structures in its own structure. It is a long strand made of 4 nucleotides - this is the code of life. It goes ACGTTCCTCCCGGGCTCC, and so on, and so on, and so on. If you know the code you know the structure of all living things, at least in theory. The 3-dimensional structure of the DNA double helix. Ref:http://www.staff.uni-mainz.de/cfrosch/bc4s/students

4. DNA These are the four standard nucleotide bases adenine (A), thymine (T), guanine (G), and cytosine (C). Here, they are all attached to sugar and phosphate (on the left, the violet "star" is phosphor). Sugar and phosphate can be bonded ("glued") together. This makes the assembly of the nucleotides into a long strand possible. The strand has a backbone made of sugar and phosphate, and the nucleotide bases are like washed laundry on a clothes-line, as below. Finally, two such lines can build a double helix as in DNA Two strands of linked nucleotides with one of the four bases adenine(A),Thymine(T),guanine(G) and cytosine(C). Ref:http://www.staff.uni-mainz.de/cfrosch/bc4s/students

5. RNA RNA is a polymer of ribonucleoside-phosphates. It's backbone is comprised of alternating ribose and phosphate groups. Ribose is a five carbon sugar that is found in a puranose, or five-membered ring, form in RNA. The phosphate groups link consecutive ribose groups and each bear one negative charge. Each monomer also has a nitrogenous base for a side chain. The four commonly found side chains in RNA are adenine, cytosine, guanine and uracil. Several other bases are occasionaly found in RNAs including: thymine, pseudouridine and methylated cytosine and guanine. There are three major types of RNA: messenger RNA (mRNA), transfer RNA (tRNA) and ribosomal RNA (rRNA). There are a number of other types of RNA present in smaller quanitites as well, including small nuclear RNA (snRNA), small nucleolar RNA (snoRNA) and the 4.5S signal recognition particle (SRP) RNA. Novel species of RNA continue to be identified. RNA serves a multitude of roles in living cells. These include: serving as a temporary copy of genes that is used as a template for protein synthesis (mRNA), functioning as adaptor molecules that decode the genetic code (tRNA) and catalyzing the synthesis of proteins (rRNA). There is much evidence implicating RNA structure in biological regulation and catalysis. Interestingly, RNA is the only biological polymer that serves as both a catalyst (like proteins) and as information storage (like DNA). For this reason, it has be postulated RNA, or an RNA-like molecule, was the basis of life early in evolution. Ref:http://www.rnabase.org

6. Protein • Polypeptide:made up of a sequence of amino acids • Folds to form a complex 3-D structure. • The function of a protein is a consequence of its folded state. • Has unique functions in the cell.Examples: are • hormones,enzymes and antibodies Fig:Structure of four of the 20 amino acids Fig Ref:http://www.staff.uni-mainz.de/cfrosch/bc4s/students/aminos.html

7. Protein structure Proteins are polypeptides composed of amino acid residues interlinked by amide bonds. Their structure can be discussed in terms of four levels of : • Primary Structure: refers to the "linear" sequence of amino acids. • Secondary structure is "local" ordered structure brought about via hydrogen bonding mainly within the peptide backbone. • Tertiary Structure:It is the global folding of a single polypeptide chain • Quaternary structure:This involves the association of two or more polypeptide chains into a multi subunit structure Fig Ref:http://www.bmb.uga.edu/wampler/tutorial/prot0.html

8. Gene A gene (made from DNA) is the code to build a protein The process to build a protein is called gene expression

9. Central Dogma • Transcription:the synthesis of an RNA copy from a sequence of DNA, is carried out by an enzyme called RNA polymerase. This molecule has the job of recognizing the DNA sequence where transcription is initiated, called the promoter site. In general, there are two "promoter" sequences upstream from the beginning of every gene. The location and base sequence of each promoter site vary for prokaryotes (bacteria) and eukaryotes (higher organisms), but they are both recognized by RNA polymerase, which can then grab hold of the sequence and drive the production of an mRNA.Eukaryotic cells have three different RNA polymerases, each recognizing three classes of genes. RNA polymerase II is responsible for synthesis of mRNAs from protein-coding genes. This polymerase requires a sequence resembling TATAA, commonly referred to as the TATA box, which is found 25-30 nucleotides upstream of the beginning of the gene, referred to as the initiator sequence.Transcription terminates when the polymerase stumbles upon a termination, or stop signal. In eukaryotes, this process is not fully understood. Prokaryotes, however, tend to have a short region composed of G's and C's that is able to fold in on itself and form complementary base pairs, creating a stem in the new mRNA. This stem then causes the polymerase to trip and release the nascent, or newly formed, mRNA.  • Translation: The beginning of translation, the process in which the genetic code carried by mRNA directs the synthesis of proteins from amino acids, differs slightly for prokaryotes and eukaryotes, although both processes always initiate at a codon for methionine. For prokaryotes, the ribosome recognizes and attaches at the sequence AGGAGGU on the mRNA, called the Shine-Delgarno sequence, that appears just upstream from the methionine (AUG) codon. Curiously, eukaryotes lack this recognition sequence and simply initiate translation at the amino acid methionine, usually coded for by the bases AUG, but sometimes GUG. Translation is terminated for both prokaryotes and eukaryotes when the ribosome reaches one of the three stop codons. The "Central Dogma"—a fundamental principle of molecular biology—states that genetic information flows from DNA to RNA to protein. Ultimately, however, the genetic code resides in DNA because only DNA is passed from generation to generation. Yet, in the process of making a protein, the encoded information must be faithfully transmitted first to RNA then to protein. It consists of two steps:Transcription and Translation

10. Introns and Exons • Intron:Non coding portions of a gene • Exon:Coding portions of a gene Genes make up about 1 percent of the total DNA in our genome. A eukaryotic gene does not code for a protein in one continuous stretch of DNA. Both exons and introns are "transcribed" into mRNA, but before it is transported to the ribosome, the primary mRNA transcript is edited. This editing process removes the introns, joins the exons together, and adds unique features to each end of the transcript to make a "mature" mRNA. It is still unclear what all the functions of introns are, but scientists believe that some serve as the site for recombination, the process by which progeny derive a combination of genes different from that of either parent, resulting in novel genes with new combinations of exons, the key to evolution.

11. Advance Molecular Biology Tutorial Resources: • http://www.kyb.mpg.de/publications/pdfs/pdf2503.pdf • http://www.esp.org/misc/genome/primer.pdf