Basic Biology

This section is meant solely for the quantitatively trained scientist who knows essentially none of the biology developed over the last three decades. For those of you who need a significant refresher in molecular biology we list several good introductory texts and on-line resources (table 1.1). So we start from the beginning. In almost all cells making up a living organism, there is believed to be an identical set of codes describing the genes and their regulation. This code is encoded as one or more strands of the deoxyribonucleic acid molecule: DNA. That is the same in almost every cell in the human body.[9] For instance, a liver cell and a brain cell have the same DNA content and code in their nucleus. What distinguishes these cells from one another is that portion of their DNA that is transcribed and translated into protein, as described below.

Table 1.1: Molecular biology primers

T. A. Brown & Austen Brown. New York, Wiley-Liss, 1999.

• Human Molecular Genetics, 2nd edition.

Tom Strachan & Andrew Read. New York, Wiley-Liss,

1999.

• Primer on molecular genetics http://www.bis.med.jhmi.edu/Dan/DOE/intro.html.

• Primer on genomics with a commercial flavor http://www.biospace.com/articles/genomics.primer.cfm

• Introductory biology course at MIT (7.01) hypertext book

http://www.esg-www.mit.edu:8001/esgbio/701intro.html

The entire complement of DNA molecules of each organism is also known as its genome. The overall function of the genome is to drive the generation of molecules, mostly proteins, that will regulate the metabolism of a cell and its response to the environment, as well as provide structural integrity.

Structure of DNA Each molecule of DNA maybe viewed as a pair of chains of the nucleotides adenine (A), thymine (T), cytosine (C), and guanine (G). Moreover, each chain has a polarity, from 52 (head) to 32 (tail). The two strands join in opposing polarity(52 binds to 32) through the coordinated force of multiple hydrogen bonds at each base-pairing, where A binds to T and C binds to G. [10]

DNA is able to undergo duplication, which occurs through the coordinated action of many molecules, including DNA polymerases (synthesizing new DNA), DNA gyrases (unwinding the molecule), and DNA ligases (concatenating segments together).

Transcription of DNA into RNA In order for the genome to direct or effect changes in the cytoplasm of the cell, a transcriptional program may be activated for the purpose of generating new proteins to populate the cytosol—the heterogenous intracellular soup of the cytoplasm. DNA remains in the nucleus of the cell, while most proteins are needed in the cytoplasm of the cell, where many of the cell's functions are performed. Thus, DNA is copied into a more transient molecule called RNA. [11] A gene is a single segment of the coding region that is transcribed into RNA. RNA is generated from the DNA template in the nucleus of the cell through a process called transcription.[12]

The RNA sequence of base pairs generated in transcription corresponds to that in the DNA molecules using the complementary A-T, C-G, with the principal distinction being that the nucleotide uracil is substituted for the thymine nucleotide. Thus, the RNA alphabet is ACUG instead of the DNA alphabet ACTG. Each cell contains around 20 to 30 pg of RNA, which represents 1% of the cell mass. The RNA that codes for proteins is called messenger RNA, and the part of the DNA that provides that code is called an open reading frame (ORF). When read in the standard 52 to 32 direction, the portion of DNA before the ORF is considered upstream, and the portion following the ORF is considered downstream.

The specific determination of which genes to transcribe is determined by promoter regions, which are DNA sequences upstream of an ORF. Many proteins have been found containing parts that bind to these specific promoter regions, and thus activate or deactivate transcription of the downstream ORF. These proteins are called transcription factors.[13]

A diagram of the genetic information flow, from DNA to RNA to protein, is illustrated in Figure 1.7

Figure 1.7: Flow of genetic information, from DNA to RNA to protein. This simplified diagram shows how the production of specific proteins is governed by the DNA sequence through the production of RNA. Many stimuli can activate the specific transcription of genes, and proteins can play a wide variety of roles within or outside cells. Note that even in this simplified model, it is obvious that since we are currently able to (nearly) comprehensively measure only gene expression levels, we are missing comprehensive measurements of protein modification, activity, transcriptional stimuli, and many other components of the state of a cell.

Prokaryotic and eukaryotic cell types Although there are many taxonomies one could use, we can essentially divide the world of organisms into two types: eukaryotes, whose cells contain compartments or organelles within the cell, such as mitochondria and a nucleus; and prokaryotes, whose simpler cells do not have these organelles. Animals and plants are examples of eukaryotes, while bacteria are prokaryotes. Most prokaryotes have a smaller genome, typically contained in a single circular DNA molecule. Additional genetic information may be contained in smaller satellite pieces of DNA, called plasmids.

Figure 1.7: Flow of genetic information, from DNA to RNA to protein. This simplified diagram shows how the production of specific proteins is governed by the DNA sequence through the production of RNA. Many stimuli can activate the specific transcription of genes, and proteins can play a wide variety of roles within or outside cells. Note that even in this simplified model, it is obvious that since we are currently able to (nearly) comprehensively measure only gene expression levels, we are missing comprehensive measurements of protein modification, activity, transcriptional stimuli, and many other components of the state of a cell.

Prokaryotic and eukaryotic cell types Although there are many taxonomies one could use, we can essentially divide the world of organisms into two types: eukaryotes, whose cells contain compartments or organelles within the cell, such as mitochondria and a nucleus; and prokaryotes, whose simpler cells do not have these organelles. Animals and plants are examples of eukaryotes, while bacteria are prokaryotes. Most prokaryotes have a smaller genome, typically contained in a single circular DNA molecule. Additional genetic information may be contained in smaller satellite pieces of DNA, called plasmids.

The structure and processing of RNA transcripts Eukaryotic genes are not necessarily continuous; instead, most genes contain exons (portions that will be placed into the mRNA) and introns (interruptions that will be spliced out). Functions have been recently discovered for introns, such as promoter-like control of the transcription process. Introns are not always spliced consistently; if an intron is left in the mRNA, an alternative splicing product is created. Various tissue types can flexibly alter their gene products through alternative splicing. [14]

Before coding RNA is ready as mRNA, the pre-mRNA must be processed.'151 In eukaryotes, after the splicing process, the generated mRNA molecule is actively exported through nuclear pore complexes into the cytoplasm. The cytoplasm is where the cellular machinery, in particular the ribosomal complex,'16' acts to generate the protein on the basis of the mRNA code. A protein is built as a polymer or chain of amino acids, and the sequence of amino acids in a protein is determined by the mRNA template. The mRNA provides a degenerate coding in that it uses three nucleotides to code for each of the twenty common naturally occurring amino acids that are joined together to form the polypeptide or protein molecule. With three nucleotides there can be 43 possible combinations for a total of 64 combinations. Consequently, several trinucleotide sequences (also known as codons) correspond to a single amino acid. There is no nucleotide between codons, and a few codons represent start (or initiation) and stop (or termination).'171 The process of generating a protein or polypeptide from an mRNA molecule is known as translation.

As an example, if an RNA transcript had the nucleotide sequence

Was this article helpful?

0 0

Post a comment