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and we'll post brief responses from researchers.
In the type of cell division that forms eggs
and sperm, replication of DNA is immediately
followed by an exchange of genetic material between
matching paternal and maternal chromosomes. How
do matching chromosomes recognize each other and
stick together to ensure that genes are swapped
properly?
—Katarzyna Drzewicka, student, Poland
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Response
by Andreas Hochwagen
Whitehead Fellow |
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Your question is a good one. How matching chromosomes
find each other before they are distributed during
meiosis and packaged into sperm or eggs is still not
very well understood. A number of labs around the world,
including my own here at the Whitehead, are conducting
experiments to investigate this process.
The problem of correctly pairing up matching DNA sequences
is profound. Even small genomes contain millions of
base pairs of DNA (the baker's yeast genome, which
we use for our studies, contains about 12 million).
For small organisms, the process of aligning the matching
sequences is comparable to finding matching book pages
in two piles of about 40,000 pages. For a human
cell with a genome of about 3 billion base pairs, this
amounts to about 10 million pages in each pile. Yet
human cells complete this task in two to three days
and budding yeast cells take only about one hour.
There are several mechanisms that appear to collaborate
in rapidly sorting the DNA and aligning chromosomes.
Some are working at the level of entire chromosomes.
For example, in many organisms the chromosome ends
get bundled into a conformation known as the "bouquet" prior
to meiosis. It is thought that this spatial restriction
of chromosomes helps to reduce the space that needs
to be searched for a matching partner.
Furthermore, some organisms, such as fruit flies or
round worms, appear to have what amounts to identifier
sequences. These so-called "pairing centers" are
unique for each chromosome. A family of proteins that
selectively bind to each of these pairing centers then
act as glue to bind matching chromosomes to each other.
However, pairing centers have not been found in humans
or other mammals.
Large-scale alignment of chromosomes alone is not
sufficient to correctly link meiotic chromosomes together
because chromosomes also have to be paired at the DNA
sequence level. The best understood mechanism involves
the formation of single-strandedDNA at spots where
the doublestranded structure breaks down. The sequences
of these stretches of single-stranded DNA are then
used to scan the genome (although how this scanning
actually works on a mechanistic level is still not
known).
The scanning is highly efficient but also quite error-prone
because only short sequence stretches are analyzed
by the cell. We know this because the cell occasionally
makes mistake, pairing up matching sequences from the
wrong chromosomesf there are multiple identical short
sequences dispersed throughout the genome. It is thought
that the larger-scale pairing mechanisms help to reduce
the occurrence of these incorrect pairings by placing
the matching chromosomes in each other's vicinity.
In summary, while we have some idea of how the process
of chromosome pairing works during meiosis, more experiments
will be necessary to get an understanding of how these
search mechanisms actually conduct their queries. An
important question, because after all, these mechanisms
ultimately make sure that sperm and eggs get the correct
number of chromosomes.
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