Aging and Sex, DNA Repair in
81
3.6
Meiotic Recombination in Eukaryotes
Probably Evolved from Recombination in
Prokaryotes
Several workers have suggested that the
processes of recombination in prokaryotes
and eukaryotes share a common ancestry.
Dougherty in 1955 may have been the Frst
to conclude that the evolution of sexuality
as it exists today was the result of a sin-
gle phylogenetic sequence. He based this
conclusion on the fact that recombination
in bacteriophage and in bacteria, on the
one hand, and meiotic recombination in
eukaryotes, on the other hand, seemed to
share fundamental similarities. Later Stahl
in 1979 also concluded that despite numer-
ous differences in detail, the ‘‘similarities
in recombination in creatures as diverse
as the phage and fungi are impressive.’’
In recent years, there has been con-
siderable work on the biochemistry of
recombination, with an emphasis on the
RecA protein of the bacterium
Escherichia
coli
. This protein catalyzes the key steps in
recombination of homologous DNA pair-
ing and strand exchange. Homologs of
the
E. coli RecA
gene have been identi-
Fed in over 60 bacterial species and in
bacteriophage T4, suggesting that RecA-
catalyzed recombination is very common
in the prokaryotic world. Since about 1992,
there has been much work indicating that
RecA homologs play a key role in meiotic
recombination in fungi and vertebrates.
A RecA homolog in humans shows 30%
amino acid sequence identity with the
E. coli
RecA protein. RecA homologs in
yeast and humans form helical Flaments
with DNA, such as those formed by
E.
coli
RecA, leading to the conclusion that
the RecA protein has been conserved from
bacteria to man. These Fndings suggest
that eukaryotic meiotic recombination and
recombination processes in extant bacteria
are probably both derived from a common
ancestor that existed before the divergence
of prokaryotes and eukaryotes, at least
1.8 billion years ago.
3.7
Homologs of the Bacterial RecA Protein
Have a Key Role in Eukaryotic Meiotic
Recombinational Repair
Substantial evidence indicates that RecA
homologs have a central role in recombina-
tional repair during meiosis in yeast. The
yeast
rad
51 and
dmc1
genes are homologs
of the
recA
gene of
E. coli.
The Rad51 and
Dmc1 proteins probably share redundant
functions, since recombination is reduced
by only a few fold in
dmc1
and
rad51
sin-
gle mutants, but
dmc1
and
rad51
double
mutants are profoundly defective in mei-
otic recombination. The Rad51 protein acts
during both mitosis and meiosis, whereas
Dmc1 protein acts only during meiosis.
Both Rad51 and Dmc1 proteins function
in repair of double-strand breaks. Sung
in 1994 demonstrated that Rad51 protein,
like
E. coli
RecA protein, catalyzes ATP-
dependent homologous DNA pairing and
strand exchange. The Dmc1 protein has an
overall similarity to
E. coli
RecA protein in
tertiary structure. These Fndings suggest
that the yeast Rad51 and the bacterial RecA
proteins have similar functions in recom-
binational repair. Morita and coworkers
showed in 1993 that in the mouse a
recA
homolog is expressed at high level in the
testes. Shinohara and coworkers in 1993
also showed that the mouse
recA
homolog
is expressed at a high level in the testis
and ovary, and suggested that the protein
product of this gene is involved in meiotic
recombination. The expression of a
recA
gene homolog has also been demonstrated
in chicken testis and ovary and in human
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