8.4: Chromosomes

It was clear by the twentieth century that eukaryotic nuclei were somehow involved in inheritance and further, that the behavior of paired chromosomes in meiosis mimicked the behavior of Mendel’s heritable factors. Hence, the chromosome theory of heredity, which posits that chromosomes contain genes. Let’s take a brief look at how we came to know this. As with much of genetics, it begins with Mendel! Mendel could not account for deviations from his Law of Independent Assortment— e.g., an unexpected green pea plant among the many yellow pea plants expected from a genetic cross. But, in the early 1900s, genetic studies of Drosophila melanogaster in Thomas Hunt Morgan’s lab showed that Mendel’s misbehaving pea plant traits were due to recombination (crossing over) between bits of homologous chromosomes during meiosis. Furthermore, these crossings over were frequent. In fact, the recombination frequency of a given pair of genes was reproducible, effectively a constant. This suggested that such gene pairs were linked on the same chromosome, consistent with chromosome theory. For this work, Morgan earned the 1933 Nobel Prize for Physiology or Medicine. He further suggested that genes far apart on a chromosome would cross over more often than those closer together. Alfred H. Sturtevant (one of Morgan’s students) tested the possibility that recombination frequencies might be used to map the position (locus) of genes on chromosomes. He confirmed this by generating the first maps of D. melanogaster’s four chromosomes! See D. melanogaster Gene Mapping (or I. Lobo & K. Shaw, 2008; T. H. Morgan, Genetic recombination, and gene mapping. Nature Educ. 1:205) for more details.) Let’s look at a typical chromosome (Figure 8.9).

Figure 8.9: A female chromosome stained for with banding and defining a centromere and two telomeres.

Late nineteenth-century microscopists saw chromosomes condense a dispersed state as the nucleus broke down during mitosis or meiosis. They were visible as they moved to opposite poles of the cell during cell division. Look at chromatids separating in mitotic anaphase in the computer-colorized micrograph at Chromatid Separation in Anaphase.

CHALLENGE

Why are virtually all genes in dividing cells inactive?

It’s possible to distinguish one chromosome from another by karyotyping. Cells in metaphase of mitosis placed under pressure will burst and the chromosomes spread out. Figure 8.10 shows such a chromosomal spread.

Figure 8.10: Spread of human mitotic cell chromosomes.

Such spreads showed that chromosomes come in matched pairs, again parallel to Mendel’s paired heritable factors. By the early 1900s, the number, sizes, and shapes of chromosomes were known to be species-specific. Cutting apart micrographs like the ones in Figures 8.10 and 8.11, and then pairing the chromosomes by their morphology, generates a karyotype. Paired human homologs are easily identified in the modern colorized micrograph (Figure 8.11).

Figure 8.11: Computer-colorized human chromosome spread (right) and karyotype (inset at left). An intact nucleus is seen above the karyotype.

As seen in cells undergoing mitosis, all dividing human cells contain twenty-three pairs of homologous chromosomes. The karyotype in Figure 8.11 is from a female; note the pair of homologous sex (X) chromosomes (lower right of the inset). X and Y chromosomes in males are not truly homologous. Chromosomes in the original spread and in the aligned karyotype were stained with fluorescent antibodies against chromosome-specific DNA sequences to ”light up” the different chromosomes.

171-2 DNA, Chromosomes, Karyotypes, & Gene Maps