Sex-linked Genes Continued

Table of Contents

X Inactivation

The mammalian X-chromosome contains significantly more genetic information than the Y-chromosome. This gene dosage is controlled for in females through a process called X-inactivation where one of the X-chromosomes is shut down and highly condensed into a Barr body.

Inactivation of the X-chromosome occurs in a stochastic manner that results in females being cellular mosaics where a group of cells have inactivated the paternal X-chromosome and other patches of cells have inactivated the maternal X-chromosome. The most striking example of mosaicism is the calico cat. A calico cat (tortoise shell cat) is always a female. One of the genes that encodes coat color in cats resides on the X-chromosome and exist as either orange or black alleles. Due to the stochastic inactivation, the patterning of orange and black fur is a distinctive quality of calicos.

Calico Cat — The top two images show an orange cat and a tabby cat with black markings. The lower image shows a calico cat that has inherited one X chromosome with the orange fur allele and one X chromosome with the black fur allele.

While the genetic information for the the orange or black coat color exists in all cells, they are not equally expressed. This type of heritable trait in spite of the presence of the genetic material (DNA) is called epigenetic to imply that it is “above” (epi) genetics .

Drosophila: Thomas Hunt Morgan

Around 1908, Thomas Hunt Morgan began to explore the genetics of what was to become a model organism, Drosophila melanogaster (fruit fly). This small organism had a relatively short life cycle, great fecundity and was easily managed. From these flies that normally have red eye coloring, he and his students found white-eyed mutants. The lab noted that white-eyed flies were almost exclusively male. This gender imbalance lead Morgan to believe that the trait was sex-linked. In 1911, Morgan published a paper that described the inheritance patterns of 5 eye-colors in Drosophila (Morgan, 1911).

Drosophila follow a sex determination based on the the ratio of X:A chromosomes and not by the presence of a Y as in mammals. A 1:1 ratio results in a female and a 1:2 ratio results in a male where the Y is ignored. The standard 2N = 8.

Eye colors (clockwise): brown, cinnabar, sepia, vermilion, white, wild. Also, the white-eyed fly has a yellow body, the sepia-eyed fly has a black body, and the brown-eyed fly has an ebony body. White-eyed flies have a gender imbalance and occur mostly in males.

While DNA was not yet known as the source of genetic information, Morgan’s studies revealed that the location of genes most likely resided on the chromosomes. By cataloging many mutations in the lab, he was able to construct a map of gene locations. His 1922 paper specifically stated that some traits were sex-linked and therefore residing on the sex chromosome.

When performing crosses of white-eyed males to wild-type females, he continued to find white-eyed trait only in males. However, in the subsequent cross of females from that generation with white-eyed males, the presence of white-eyed males and females were revealed. This indicated that the white-eyed trait was recessive and resided on the X chromosome.

*Analysis of the transmission of “White-Eyed” color in Drosophila*.

Morgan received the Nobel Prize in Physiology or Medicine in 1933 for his inference of chromosomes being a physical mechanism for packaging genetic information in the cells.