Repetitive sequences

Figure 14.9 Spicier fibers are composite materials formed by large silk fibroin polypeptide chains with repetitive sequences that form p sheets. Some regions of the chains participate in forming 100-nm crystals, while other regions are part of a less-ordered mesh-work in which the crystals are embedded. The diagram shows a model of the current concepts of how these fibers are built up, which probably will be modified and extended as new knowledge is gained. (Adapted from F. Vollrath, Sci. Am. p. 54-58, March 1992 and A.H. Simmons, Science 271 84-87, 1996. Photograph courtesy of Science Photo Library.)...

The long, repetitive sequence of —N—CH-CO- atoms that make up a continuous chain is called the protein s backbone. By convention, peptides are written with the N-terminal amino acid (the one with the free -NH3 1 group) on the left and the C-terminal amino acid (the one with the free -C02 group) on the right. The name of the peptide is indicated by using the abbreviations listed in Table 26.1 for each amino add. Thus, alanylserine is abbreviated Ala-Ser or A-S, and serylalanine is abbreviated Ser-Ala or S-A. Needless to say, the one-letter abbreviations are more convenient than the older three-letter abbreviations. 

The general idea of peptide sequencing by Edman degradation is to cleave one amino acid at a time from an end of the peptide chain. That terminal amino acid is then separated and identified, and the cleavage reactions are repeated on the chain-shortened peptide until the entire peptide sequence is known. Automated protein sequencers are available that allow as many as 50 repetitive sequencing cycles to be carried out before a buildup of unwanted by products interferes with the results. So efficient are these instruments that sequence information can be obtained from as little as 1 to 5 picomoles of sample—less than 0.1 /xg. 

Examples of a polymorphism include single nucleotide substitutions, insertions and deletions of nucleotides, and repetitive sequences. While most polymorphisms are harmless and part of normal human genetic variations, studies have established links between certain gene polymorphisms and metabolic alterations or human diseases. 

The DNA in a eukaryotic genome can be divided into different sequence classes. These are unique-sequence, or nonrepetitive, DNA and repetitive-sequence DNA. In the haploid genome, unique-sequence DNA generally includes the single copy genes that code for proteins. The repetitive DNA in the haploid genome includes sequences that vary in copy number from two to as many as 10 copies per cell. 

This estimation (and the distribution of repetitive-sequence DNA) is based on a variety of DNA-RNA hybridization techniques and, more recently, on direct DNA sequencing. Similar techniques are used to estimate the number of active genes in a population of unique-sequence DNA. In brewers yeast Saccha-romyces cerevisiae, a lower eukaryote), about two thirds of its 6200 genes are expressed. In typical tissues in a higher eukaryote (eg, mammalian liver and kidney), between 10,000 and 15,000 genes are expressed. Different combinations of genes are expressed in each tissue,... 

In Human DNA, at Least 30% of the Genome Consists of Repetitive Sequences... 

Repetitive-sequence DNA can be broadly classified as moderately repetitive or as highly repetitive. The highly repetitive sequences consist of 5-500 base pair lengths repeated many times in tandem. These sequences are usually clustered in centromeres and telomeres of the chromosome and are present in about 1-10 milHon copies per haploid genome. These sequences are transcriptionally inactive and may play a strucmral role in the chromosome (see Chapter 40). 

The moderately repetitive sequences, which are defined as being present in numbers of less than 10 copies per haploid genome, are not clustered but are interspersed with unique sequences. In many cases, these long interspersed repeats are transcribed by RNA polymerase II and contain caps indistinguishable from those on mRNA. 

Braun, V. Bosch, V. Repetitive sequences in the murein-hpoprotein of the cell wall of Escherichia coli. Proc. Nat. Acad. Sci. USA 1972, 69, 970-974. 

Kane, R.A and Rollinson, D. (1994) Repetitive sequences in the ribosomal DNA internal transcribed spacer of Schistosoma haematobium, Schistosoma intercalatum and Schistosoma matthei. Molecular and Biochemical Parasitology 63, 153—156. 

Stallings RL, Ford AF, Nelson D, Tor-ney DC, Hildebrand CE, Moyzis RK. Evolution and distribution of (GT)n repetitive sequences in mammalian genomes. Genomics 1991 10 807-815. 

Silk proteins (spidroins in spiders and fibroins in Lepidoptera insects) are assembled into well-defined nanofibrillar architectures (Craig and Riekel, 2002 Eby et al., 1999 Inoue et al., 2000b, 2001 Li et al., 1994 Putthanarat et al, 2000 Vollrath et al., 1996). Spidroins and fibroins are largely constructed from two chemically distinct repetitive motifs or blocks (Table I), an insoluble crystalline block and a soluble less-crystalline block (Craig, 2003 Fedic et al., 2002 Hayashi and Lewis, 2000 Hayashi et al., 1999). The crystalline blocks are composed of short side-chained amino acids in highly repetitive sequences that give rise to /1-sheet structures. 

We note that sequence repeats may be deleted as quickly as they are inserted. Thus, repetitive sequences are well suited to respond rapidly to environmental changes (Buard and Vergnaud, 1994). This property may contribute to the abundance of /1-solenoids at bacterial and viral surfaces. 

Reverse transcription, which produces DNA copies of an RNA, is more commonly associated with life cycles of retroviruses, which replicate and express their genome through a DNA intermediate (an integrated provirus). Reverse transcription also occurs to a limited extent in human cells, where it plays a role in amplifying certain highly repetitive sequences in the DNA (Chapter 7). 

Encoded by retrotransposons (residual viral genomes permanently maintained in human DNA) that play a role in amplifying certain repetitive sequences in DNA (see Chapter 7). 

Expansion of repetitive sequences (minisateflites or VNTRs, variable number of tandem repeats) within the DNA... 

Several types of repetitive sequences have been identified in chromosomes. Generally, but not always, these are found in the noncoding (spacer) DNA, The following classes are distinguished ... 

Most repetitive sequences are not in coding regions. Because expansion of these sequences in spacer DMA rarely affects any function, they become highly polymorphic in the population and can be used to develop a genetic fir erprint. Such fingerprints are important in paternity testing and forensic medicine. Very small samples containing dried tissue can be analyzed by this technique. 

Diversity mutations in RE sites and expansion of repetitive sequences... 

Inhibition of the Ubiquitin-Proteasome System by a Viral Repetitive Sequence... 

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