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)
Fig. 5.14.1 Chromosomes courtesy of J. Bodycote and S. Wolff
This image demonstrates that (1) each chromosome contains but a single molecule of DNA and (2) the replication of a chromosome is semi-conservative (just as is the replication of a single DNA molecule). The information encoded in each strand of DNA remains intact as it serves as the template for the assembly of a complementary strand.
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 in Figure 5.14.1). 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 in Figure 5.14.1, are explained below.)
On occasions, sister chromatids spontaneously exchange segments. The exchange is reciprocal. 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.
Barring reciprocal exchanges and mutations, 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.
Fig. 5.14.2 Immortal Strands
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:
- one that will continue as a stem cell and
- one that will go on to differentiate.
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. 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
- only certain chromosomes (e.g., the X and Y in Drosophila male germline stem cells) preferentially segregate the parental chromatids to the cell that will remain a stem cell;
- and for others, the distribution of immortal strands at metaphase is random, and thus the drawing on the right does not reflect what happens in those cases.