Chromosomal Theory of Inheritance

The physical question behind Mendel's factors

Mendel's experiments showed that inherited factors behave as stable units, but did not identify their physical location. Around 1900, further experiments reproduced his results, while improved microscopy made chromosome behaviour in dividing cells visible. Sutton and Boveri proposed that chromosomes supplied the physical basis for inheritance because chromosome pairs and allele pairs behaved in parallel. Chromosomes occurred in pairs in diploid cells, one member of each pair went into a gamete, and different pairs could separate independently. This correspondence became the chromosomal theory of inheritance, a bridge between observations of offspring and structures within cells.

Genes are arranged on chromosomes

A chromosome is a long DNA molecule associated with proteins. Genes occupy specific positions called loci on chromosomes. Homologous chromosomes carry corresponding loci but can hold different alleles. In a heterozygote Tt, one homologue carries T at the height locus and the other carries t. Before division, each chromosome is replicated into two sister chromatids joined at the centromere. Sister chromatids are copies of one chromosome after replication; homologues are the maternal and paternal members of a chromosome pair. Confusing chromatids with homologues can lead to incorrect predictions about what separates during meiosis I.

Meiosis I explains segregation

In meiosis I, homologous chromosomes pair and subsequently move to opposite poles. Because the two alleles of an autosomal locus reside on opposite homologues, their separation places one allele into each daughter cell. This gives a physical explanation for Mendel's segregation principle. DNA replication does not double the final number of allele types carried in each gamete. The second division, meiosis II, separates sister chromatids; the mature products are haploid. Fertilisation joins haploid gametes and restores paired homologues. A diagram should distinguish the reduction in chromosome sets during meiosis I from chromatid separation during meiosis II.

Independent alignment explains assortment

At metaphase I, each pair of homologues can face the poles in either orientation. The orientation of one homologous pair is generally independent of another pair's orientation. Thus a gamete may receive a maternal copy of one chromosome and a paternal copy of another, or the reverse. With two independently orienting homologous pairs, four combinations of chromosome origins are possible before accounting for crossing over. This underlies independent assortment for loci on different chromosomes. The number of possible chromosome combinations from independent assortment alone is 2^n, where n is the number of homologous pairs, assuming ordinary disjunction and ignoring recombination.

Two separate mechanisms create variation

Independent assortment recombines whole homologous chromosome origins between gametes, while crossing over exchanges DNA segments between nonsister chromatids of homologues during prophase I. Crossing over can create new allele combinations within a chromosome. Together with random fertilisation, these mechanisms explain why siblings differ despite sharing parents. It is misleading to say every gene on a chromosome independently assort with every other gene: nearby loci are physically linked. The chromosomal theory therefore supports Mendel's findings but also exposes the conditions under which his simplest ratios have limitations.

Why fruit flies advanced genetic reasoning

Thomas Hunt Morgan and collaborators studied the fruit fly Drosophila melanogaster because it is small, breeds quickly, produces many offspring, and has observable inherited variants. They found crosses in which allele combinations departed from the proportions expected for independent assortment. Those departures helped show that genes reside at positions along chromosomes and can be inherited together. His work did not discard Mendelian inheritance; it showed how chromosome location and recombination modify the probability of allele combinations. Chromosome behaviour made inheritance experimentally testable at a finer resolution than visible phenotype alone.

A model with two chromosome pairs

Imagine diploid cell with homologous long chromosomes Lm and Lp and short chromosomes Sm and Sp. At metaphase I, orientation A can send Lm with Sm and Lp with Sp; orientation B can send Lm with Sp and Lp with Sm. If both orientations are equally likely, the four maternal/paternal combinations appear equally in the resulting gametes in the absence of other biases. An allele at a locus on the long chromosome and an allele on the short chromosome therefore have independent association. If both loci were closely positioned on the same long chromosome, that independence would not be expected.

Mendel published his findings in the nineteenth century, but they were not widely recognised immediately. Around 1900, Hugo de Vries, Carl Correns and Erich von Tschermak independently reported inheritance results consistent with Mendel's principles. Advances in microscopy then allowed researchers to observe chromosomes pairing, separating and entering gametes. Sutton and Boveri used the similarity between these chromosome movements and Mendelian allele behaviour to connect an abstract hereditary factor with a physical structure. The historical progression illustrates why an experimentally useful inheritance rule can precede knowledge of its molecular explanation.

Quick Quiz