Page 42 - Genetics_From_Genes_to_Genomes_6th_FULL_Part2

6.5 Homologous Recombination at the DNA Level 201

The Integrity of Genetic Information • At the DNA replication fork, DNA polymerase synthesizes
Must Be Preserved one new strand (the leading strand) continuously, while
the other (lagging strand) is synthesized as multiple
DNA is the sole repository of the vast amount of informa- Okazaki fragments that are then joined by DNA ligase.
tion required to specify the structure and function of most • The integrity and accuracy of information in DNA is
organisms. In some species, this information may lie in preserved by redundancy in the two strands, the
storage for many years, or it may undergo replication many precision of the enzymes synthesizing DNA, and the
times before it is called on to generate progeny. During the action of enzymes that repair damage to DNA.
time of storage and before gamete production, the organism
must protect the integrity of the information, for even the
most minor change can have disastrous consequences, such 6.5 Homologous Recombination
as causing severe genetic disease or even death. Each or- at the DNA Level
ganism ensures the informational fidelity of its DNA in
three important ways:
learning objectives
∙ Redundancy. Either strand of the double helix can
specify the sequence of the other. This redundancy 1. Summarize the evidence from tetrad analysis confirming
provides a basis for checking and repairing errors that recombination occurs at the four-strand stage and
arising either from chemical alterations sustained involves reciprocal exchange.
during storage or from rare malfunctions of the 2. Explain how we know that DNA breaks and rejoins
replication machinery. during recombination.
∙ The remarkable precision of the cellular replication 3. List the key steps of recombination at the molecular
machinery. Evolution has perfected the cellular level.
machinery for DNA replication to the point where 4. Explain why recombination events do not always result
errors during copying are exceedingly rare. For exam- in crossing-over.
ple, DNA polymerase has acquired a proofreading 5. Describe how mismatch repair of heteroduplex regions
ability to prevent unmatched nucleotides from join- can lead to gene conversion in fungal tetrads.
ing a new strand of DNA; as a result, a free nucleo-
tide is attached to a growing strand only if its base is
correctly paired with its complement on the parent Mutation, the ultimate source of all new alleles, is a rare
strand. We examine this proofreading mechanism in phenomenon at any particular nucleotide pair on a chromo-
Chapter 7.
∙ Enzymes that repair chemical damage to DNA. The some. The most important mechanism for generating ge-
cell has an array of enzymes devoted to the repair of nomic diversity in sexually reproducing species is thus the
production of new combinations of already existing alleles.
nearly every imaginable type of chemical damage. We This type of diversity increases the chances that at least
describe how these enzymes carry out their correc- some offspring of a mating pair will inherit a combination
tions in Chapter 7.
of alleles best suited for survival and reproduction in a
All of these safeguards help ensure that the informa- changing environment.
tion content of DNA will be transmitted intact from gener- New combinations of already existing alleles arise from
ation to generation of cells and organisms. However, as we two different types of meiotic events: (i) independent assort-
see next, new combinations of existing information arise ment, in which each pair of homologous chromosomes seg-
naturally as a result of recombination. regates free from the influence of other pairs, via random
spindle attachment; and (ii) crossing-over, in which two ho-
mologous chromosomes exchange parts. Independent as-
essential concepts sortment can produce gametes carrying new allelic
combinations of genes on different chromosomes, but for
• The DNA molecule is reproduced by semiconservative
replication; the two DNA strands separate, and each acts a genes on the same chromosome, independent assortment
template for the synthesis of a new complementary strand. alone will only conserve the existing combinations of alleles.
• DNA polymerase synthesizes DNA in the 5′-to-3′ Crossing-over, however, can generate new allelic combina-
direction by adding nucleotides successively onto the 3′ tions of linked genes. The evolution of crossing-over thus
end of a growing DNA chain. compensated for what would otherwise be a significant dis-
• DNA polymerase requires: (i) a supply of the four advantage of the linkage of the genes within chromosomes.
deoxyribonucleotide triphosphates, (ii) a single-stranded Historically, geneticists have used the term recombina-
DNA template, and (iii) a primer of either DNA or (in cells) tion to indicate the production of new combinations of al-
RNA with a free 3′ hydroxyl group. leles by any means, including independent assortment. But