Page 397 - Carrahers_Polymer_Chemistry,_Eighth_Edition

360 Carraher’s Polymer Chemistry

they provide lots of information and some provide function. Such segments act, as noted above, as
a kind of palaeontological record of past interactions with various bacteria and virus; they can act
as passive markers for studying mutation and selection; and they can be active providing shape and
function allowing the same sequence to behave in a different fashion because of the presence of
these junk sequences.

Repeats can be divided into five classes. First, transposon-derived repeats, some of which
have been briefly dealt with before. About 45% of our genome is derived from transposable

elements. It is possible that some of the other “unique” DNA may also be derived from ancient
transposable element copies that we have not yet recognized. Second, partially or inactive ret-
roposed copies of cellular genes called processed pseudogenes. Third, short simple repeating
sequences such as AAAAAA, CACACACACA, and so forth. Fourth, short segmental duplica-
tions that have been copied from one region of the genome into another region. These sequences
are typically 10,000–300,000 base-pairs long (10–300 kb). Fifth, blocks of tandemly repeated
sequences.
There are four types of so-called transposon-derived repeating sequences of which three trans-
pose through RNA intermediates and one transposes directly as DNA (last one considered below).
We have already identified the long interspersed elements, LINES. The second set are called SINEs,

of which the Alu’s are the only active members that exist in the human genome.

The third group is the LTR retrotransposons that are flanked by long-terminal direct repeats
that contain all the transcriptional regulatory elements. LTR genes can encode a protease, reverse
transcriptase, RNAse H, and integrase. Transposition occurs through a retroviral mechanism with
reverse transcription occurring in a cytoplasmic virus-like particle. While a wide variety of LTRs
exist it is believed that only the endogenous retroviruses (ERVs) are active in humans.
The last group of transposable elements is the DNA transposons that resemble bacterial trans-
posons. They tend to have short life spans within a species. Humans have at least seven families of
DNA transposons. Their replication is lessened by the presence of inactive copies so as the number
of inactive copies accumulate, transposition becomes less effi cient.
As part of the overall human genome, the LINEs, SINEs, LTR, and DNA retroposons make up
20%, 13%, 8%, and 3% (total of 44%) of the repeat sequences.
Such repeats are often included as “junk.” Again, the so-called junk in our genome may not be
junk but rather part of a complex of shape and electrical nature that forms the basis for the chemis-
tries of the various polymeric molecules.
This massive amount of information should not be considered as insurmountable or only mate-
rial to be marveled at but not understood. Much of the chemistry is already available to “mine” this
information successfully. Much of it is understandable in somewhat simple terms, generally only
after we have discovered the key to this simplicity. For instance, there is a marked decrease in the
frequency of the dinucleotide CpG in some areas of the genome. The deficiency is believed to be due

to the fact that most CpG nucleotides are methylated on the cytosine base and spontaneous deami-
nation of the methyl-cytosine residue creates T residues. Thus, CpG dinucleotide sequences mutate
to TpG dinucleotides. But there still remain some questions. There are certain regions or islands
where the CpG sequences exist in a nonmethylated form and where the frequency of CpG occurs
within the expected or normal rate. Why? These CpG islands are of particular interest because they
are associated with the 5′ ends of genes.
Another broad finding in examining the human genome regards the rate of recombination.

Recombination involves the cleavage and rejoining, insertion, of sequences of nucleic acids by
enzymes. In fact, recombinant DNA is the result of such recombination. In general, the average
recombination rate increases as the length of the chromosome arm decreases. Long chromosome
arms have a recombination rate that is about half that of shorter arms. Second, the recombination
rate is less near the centromere and greater in the more distance portions of the chromosomes. This
effect is most pronounced for males. The centromere is an essential site for the equal and orderly
distribution of chromosomal units during cell formation, meiosis.

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