A. Chapter Summary

          The genomes and proteomes of prokaryotes are much simpler versions of the genome and proteome of prokaryotes. They have fewer base pairs not only because they have fewer genes but also because they do not have many repetitive sequences. Prokaryote genomes consist of either circular, linear, or both circular and linear chromosomes and only have a single origin of replication. Prokaryotes also have plasmids which are relatively small pieces of circular DNA that are separated from the chromosome(s).

            Although the genome is known as the genetic material that codes for proteins the sequences that codes for proteins actually makes up only 2% of the entire genome. The rest of the genome is made up of repetitive DNA (59%), Intron DNA (24%), and unique noncoding DNA (15%).

          Transposable elements are short segments of DNA that move to different places in the genome. There are different types of transposable elements. DNA transposons are recognized by the sequence of inverted repeats on either end of the gene. Retroelements are transposable elements that move via an RNA intermediate. These are only found in eukaryotic cells and often contain genes that encode for reverse transcriptase and integrase. The function of TEs is not yet known. The selfish DNA hypothesis states that they are around because they want to be. They only cause problems when they insert themselves into the middle of an important gene which causes the gene to either not get coded or code incorrectly. Other theories are that TEs can provide a survival advantage and greater genetic variability. Transposable elements can cause gene duplications and gene deletions by causing homologous chromosomes to misalign during meiosis. Gene families are created when gene duplications occur many times and two or more homologous genes carry out the same function.

           The entire collection of proteins that a cell or organism produces is known as its proteome. Proteomes are often much larger than genomes because of alternative splicing and post-translational covalent modification. Splicing is the process where introns are taken out of the pre-mRNA. Alternative splicing is when different combinations of introns are taken out causing different mRNA sequences ultimately causing different proteins. Post-translational covalent modification include permanent and temporary modifications.

Different proteins categorized by function are metabolic enzymes, structural proteins, motor proteins, cell-signaling proteins, transport proteins, gene expression and regulatory proteins, and protective proteins.

            Bioinformatics means the use of computers, mathematical tools, and statistical techniques to record and analyze biological information. It was first developed once scientists started to realize that genes did not all work individually but instead the opposite that many genes and proteins can affect one thing. In order to look at the big picture they had to develop tools that could handle huge amounts of data and process it quickly. In the databases you can find if a sequence contain a gene, if a sequence contains a mutation that might cause a disease, where are functional sequences are located, what the amino acid sequence of the polypeptide encoded by that gene, and if there is an evolutionary relationship between two or more genetic sequences. There are many huge databases that are used around the world.

B. Useful Materials

The struggle for life of the genome's selfish architects.

This article is a review about transposable elements, their history, function, and the interactions that take place between the transposable elements and the genome. It is very similar to the information that is supplied by the book but the article goes into much more detail. Transposable elements were discovered over 50 years ago by McClintock but no one paid much attention to them. However recently in the past few decades the science community has started to increase it's interest. They play a major role in the evolution of the genome. They can also be very harmful though if they are inserted into the sequence of an important gene.

A Novel Unstable Duplication Upstream of HAS2 Predisposes to a Breed-Defining Skin Phenotype and a Periodic Fever Syndrome in Chinese Shar-Pei Dogs.

Hereditary periodic fever syndromes are characterized by recurrent episodes of fever and inflammation with no known pathogenic or autoimmune cause. In humans, several genes have been implicated in this group of diseases, but the majority of cases remain unexplained. A similar periodic fever syndrome is relatively frequent in the Chinese Shar-Pei breed of dogs. In the western world, Shar-Pei have been strongly selected for a distinctive thick and heavily folded skin. In this study, a mutation affecting both these traits was identified. Using genome-wide SNP analysis of Shar-Pei and other breeds, the strongest signal of a breed-specific selective sweep was located on chromosome 13. The same region also harbored the strongest genome-wide association (GWA) signal for susceptibility to the periodic fever syndrome (p(raw) = 2.3×10(-6), p(genome) = 0.01). Dense targeted resequencing revealed two partially overlapping duplications, 14.3 Kb and 16.1 Kb in size, unique to Shar-Pei and upstream of the Hyaluronic Acid Synthase 2 (HAS2) gene. HAS2 encodes the rate-limiting enzyme synthesizing hyaluronan (HA), a major component of the skin. HA is up-regulated and accumulates in the thickened skin of Shar-Pei. A high copy number of the 16.1 Kb duplication was associated with an increased expression of HAS2 as well as the periodic fever syndrome (p<0.0001). When fragmented, HA can act as a trigger of the innate immune system and stimulate sterile fever and inflammation. The strong selection for the skin phenotype therefore appears to enrich for a pleiotropic mutation predisposing these dogs to a periodic fever syndrome. The identification of HA as a major risk factor for this canine disease raises the potential of this glycosaminoglycan as a risk factor for human periodic fevers and as an important driver of chronic inflammation.