Repeated sequences interspersed

Several collagen types do not form fibrils in tissues (Table 48—2). They are characterized by interruptions of the triple hehx with stretches of protein lacking Gly-X-Y repeat sequences. These non-Gly-X-Y sequences result in areas of globular structure interspersed in the triple hehcal structure. 

In humans, the LINE and Alu families account for about 60% of all interspersed repeat sequences, but there are no dominant families in the other species thus far studied. Alu segments compose about l%i-3%i of the total DNA and Alu and similar dispersed repeating sequences comprise about 5%i-10%i of human DNA. 

There are four types of transposon-derived repeating sequences, of which three transpose through RNA intermediates and one transposes directly as DNA (the last one is considered below). We have already identified the LINEs. The second set is called short interspersed elements (SINEs), of which the Alus are the only active members that exist in the human genome. 

Studies of overall genome composition based on reassociation kinetics (Simpson et ai, 1982 Cox et ai, 1990 Marx et a/., 2000) and analysis of fully sequenced bacterial artificial chromosome (BAC) clones from the 5. mansoni genome project show that platyhelminth genomes contain abundant highly and moderately repetitive sequence (Fig. 2.1). Much of the repetitive DNA comprises two classes of integrated mobile elements class I elements, which include long terminal repeat (LTR) retrotransposons and retroviruses, non-LTR retro-transposons and short interspersed nuclear elements (SINES) and transpose via an RNA intermediate, and class II elements (trans-posons), which transpose as DNA (Brindley et ai, 2003). Additionally, small dispersed or tandemly repeated sequences are common. A wide variety of these sequences have been isolated and characterized from a variety of taxa (Table 2.4). 

Fig. 10. The structure of mouse DNA containing the integrated mouse mammary tumour provirus. The integrated viral DNA can be present in many copies. The provirus contains two long terminal repeat sequences, LTR, only one of which (left) is shown in detail here. Each LTR contains sequences termed U3, R and U5 (for details, see Ref. 67). Interspersed between the LTRs are the genes named gag, pol and env, encoding viral coat proteins, reverse transcriptase and envelope proteins, respectively. The glucocorticoid-binding sequence is represented by the black box, and the transcriptional initiation area is indicated by the hatched box.

Many of the other chapters in this volume deal with evolutionary analyses of specific genes and unique DNA sequences.24-28 There are, however, some evolutionary aspects unique to repeated DNA sequences. The most important of these factors is the amplification dynamics. Sequences become repetitive because there are amplification processes that make extra copies of them. These include retroposition and transposition mechanisms that would explain the majority of interspersed repeated DNA sequences, as well as recombination or replication slippage mechanisms that would probably explain most tandem replications. For any given repeated sequence, various factors may combine to increase or decrease the amplification rate of that sequence at various times in the evolutionary process. Thus, the dynamics of the amplification process could greatly affect the observed evolution of the family. This is particularly important in cross-species comparisons, because the amplification dynamics of a specific repeated DNA family may be altered in one species, relative to another. 

Once a sequence amplification event occurs, the nature of any selection on the copies is important. In many (or even most) cases, it appears that the majority of repeated DNA sequences represent pseudogenes, which mutate at a neutral rate of evolution.8 Along with amplification dynamics, the possible removal of repeated sequences must also be considered. Removal does not seem to play a major role with the interspersed repeated DNA elements,8,29 30 but it is likely to be important in tandemly repeated satellite elements. Other mechanisms might also alter evolution of parts of a repeated DNA sequence. For instance, human Alu family copies are initially rich in CpG dinucleotides. These sites appear to be approximately 10-fold more subject to mutation than other sites in the genome,19,31... 

Second, it is important to consider whether a clone library will be representative of a particular repeated sequence. Besides the genetic factors, above, unusual patterns of restriction sites in some repeated sequences may influence their relative abundance in a library. This would be more likely for a tandemly repeated sequence or a very long repeated sequence than for short, interspersed repeated DNA sequences. Traditional A or plasmid libraries would be sufficient for most studies, but in certain situations it might be necessary to resort to DNA libraries of randomly frag-... 

All of the mammalian transposable elements that have been characterized to date seem to be the result of transpositions that proceeded through an RNA intermediate. This process is known as retrotransposition or retroposition. Three classes of these retrotransposable elements are known in mammals (1) SINEs, or short interspersed repeated sequences such as the human Alu family and rodent Bl (2) LINEs, or long interspersed repeated sequences such as LI in a variety of mammalian species and (3) retrovirus-like elements, such as THE 1 in humans and mys and IAP in rodents. Retrovirus-like elements have long terminal repeats (LTRs) that often surround two open reading frames (ORFs) like those of retroviruses, but they lack the ability to leave one cell and enter another. LINEs also have two ORFs, but have no LTRs. SINEs have no LTRs and no ORFs. Transposition of all of these elements must involve reverse transcription of the RNA intermediate in some cases the required reverse transcriptase is apparently encoded by the element itself. 

There are several large classes of DNA sequences which are not translated, including those for structural RNAs [ribosomal RNAs (rRNAs) and transfer RNAs (tRNAs)], pseudogenes, and repetitive DNAs [e.g., short and long interspersed repeated sequences (SINES and LINES)]. Ribosomal... 

Repetitive sequences are also defined by the number of base pairs in each repeated segment. Sequences that have from 100 to 500 bp are referred to as SINES (short interspersed repeated sequences) and sequences that have several thousand base pairs are referred to as LINES (long interspersed repeated sequences.) Thus, repetitive DNA sequences can be described both by the length of the segment and the degree to which it is repeated. 

By recent estimates, approximately 45% of the human genome is composed of repetitive sequences (repeated sequences of nucleotides). Although their significance is not understood, several types of repetitive sequences have been identified and investigated. There are two general classes tandem repeats and interspersed genome-wide repeats. Each is briefly described. 

Mobile DNA elements are moderately repeated DNA sequences Interspersed at multiple sites throughout the genomes of higher eukaryotes. They are present less frequently in prokaryotic genomes. 

R-banding Heat, followed by Giemsa Light Mainly GC-rich regions housekeeping genes, short interspersed repeated sequences... 

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