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O Junk DNA

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O gene

O regulatory region

O centromere

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Figure 4-3. Stereotypical chromosome structure. Bead representation of various elements labeled as in key. "Junk DNA" is a colloquialism for DNA currently of unknown function.

species and characterized by complex patterns of sequence repeats) is found; this is the centromere, which is used to separate chromosomes into daughter cells during cell division (Sun et al. 2003;Tyler-Smith and Floridia 2000). Some of this DNA has been copied and inserted into this region from elsewhere in the genome, perhaps facilitated by repeat sequences such as CAAAAAGCGGG, and in flies, at least, there are also many short AATAT and TTCTC elements in centromeres. This structure may allow the DNA to loop out from its chromosome packaging and fold up upon itself, to provide an attachment of the spindle fibers that separate the chromosomes in cell division.

Along the sequence, numerous runs of the same nucleotide (e.g., ttTTTTTTTT ...) of variable lengths or sets of tandem (adjacent) short nucleotide motifs, like (ATTT)n or (CA)n, are present. Some of the repeat copies are exactly or nearly exactly the same in different (but more or less randomly spaced) locations along a chromosome. Many of these repeated motifs have been catalogued (Vossilenko 2003). (See Table 4-1 for a sampling of these elements.) Depending on the motif or species, the repeat motif may occur tens or hundreds of thousands of times in the genome. When scanning different individuals of the same species in their corresponding chromosomal regions, one finds variation in the number of times a motif is repeated. In fact, the two sets of chromosomes in a diploid individual vary considerably in this respect. Thus, an individual may have CACACA on one chromosome and CACACACACA on the other homolog (copy of the corresponding chromosome), in a given location. These highly variable length repeats are called microsatellites (depending on the details, they are also known as short tandem repeats, or minisatellites). More than 50 percent of the human genome, in fact, consists of repeats (Lander et al. 2001). The proportion of the genome that consists of repeat regions varies considerably between species, however, from around 1 percent in some species to over 50 percent in others. The high variability in repeat numbers, within species as well as individuals, raises an important but perhaps little-appreciated point that there is no single length of the genome for a species or even in the two copies within an individual.

Some of these repeated elements have complex structures, such as a particular sequence at each end of a short (few hundred or fewer base pair) stretch of DNA, sometimes the sequence is in inverted order at the two ends, and sometimes such elements occur multiple times in tandem. Variation in short elements appears to be due to error in DNA replication during cell division. Some elements, however, are transposable, that is, have mechanisms known to make pieces of DNA move around among chromosomes from time to time, or move from parasites like viruses into a host's chromosomes. Repeat element sequences often resemble some other functional element that was captured in some way and subsequently distributed in copies around the genome. The Alu elements in primates are an example (Mighell et al. 1997); they are about 300 base pairs long and are distributed in hundreds of thousands of places in human (and other primate) genomes. The core sequence suggests that the Alu is a transposable element, including what once was a small RNA gene (Mighell, Markham et al. 1997). Sequence comparison shows a hierarchy of variation as if these elements episodically insert copies of themselves around the genome, accumulating mutations in the interim.

Clearly, selection has tolerated the presence of this repetitive DNA. It may be the harmless detritus of imperfect DNA repair or replication or of random insertions due to viruses or other "unintentional" processes manipulating DNA in the

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