Harlequin Chromosomes

Incredible though it may seem, each single human chromosome that you observe under 440x magnification of your laboratory microscope contains a single molecule of DNA. For some of our chromosomes, this molecule — if stretched out — would extend 5 cm (2 inches)!

This image demonstrates that If cells dividing in culture are treated with the pyrimidine analog bromodeoxyuridine (BrdU), during S phase, the cells are fooled into incorporating it — instead of thymidine — into their DNA.

One of the properties of the resulting DNA is that it fails to take up stain in a normal way.

When cells are allowed to duplicate their chromosomes once in BrdU, the chromosome that appear at the next metaphase stain normally.

However, when the cells duplicate their chromosomes a second time in BrdU, one of the sister chromatids that appears at the next metaphase stains normally, while its sister chromatid does not.

And note that each chromatid is normally completely stained or not (circled in red). If chromosomes were made up of numbers of different DNA molecules, we would expect to find at best a variegated pattern of stained and unstained regions and, more likely, no clear pattern at all. (The exceptions, red arrow, are explained below.)

Exceptions

On occasions, sister chromatids spontaneously exchange segments. The exchange is reciprocal.

A molecular mechanism by which this may occur is illustrated in this link.

Certain chemicals increase the frequency of these exchanges. In this image, the BrdU-treated chromosomes show many such exchanges because they were also treated with an agent that induces breaks in DNA. Repair of these breaks created reciprocal exchanges between the sister chromatids.

So now each chromatid has a pattern of alternating stained and unstained segments precisely matched with the pattern on the other chromatid.

Even when these exchanges occur spontaneously, they usually have no genetic significance because each gene has been duplicated exactly so that identical segments, carrying identical genes, are exchanged.

Both these images were provided through the courtesy of J. Bodycote and S. Wolff.

Immortal Strands

Barring

one strand of DNA in a chromosome is "immortal'; that is, it will serve as an unchanged template as it is passed on from generation to generation [Link].

Most eukaryotes have several to many pairs of chromosomes, and we might expect that at metaphase of mitosis the chromosomes would align at the metaphase plate at random so that some containing the immortal DNA strand would go to one pole; the remainder to the other.

And this is generally the case. However, there may be some exceptions.

Stem cells divide to produce two daughter cells:

There is evidence that when some types of stem cells divide, for example a subset found in skeletal muscle, the chromatids containing the immortal strand all line up on one side of the metaphase plate and the daughter cell receiving this set is the one that remains a stem cell. Although the mechanism by which this occurs is unknown, one can appreciate a potential value to the organism. Errors (mutations) in DNA occur most often during its replication [Link]. By keeping the original template in the stem cell population, introduced errors (mutations) disappear when the differentiated cell dies at the end of its useful life. Another possible advantage of nonrandom segregation of parental vs. newly-synthesized DNA: it may assure that epigenetic alterations of their respective DNA strands are transmitted to the appropriate daughter cells.

(The figure represents a haploid cell with n = 2. Each bar represents one strand of the DNA double helix.)

However, other experiments, with other types of stem cells, find that

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21 June 2013