Course Meeting Times
Lectures: 1 session / week, 2 hours / session
At least one of the following courses:
7.05 General Biochemistry
7.06 Cell Biology
7.28 Molecular Biology
What do colorblindness, Queen Victoria, and ligers (hybrids generated by male lions and female tigers) have to do with the X chromosome? This course will explore a diverse collection of striking biological phenomena associated with the X chromosome. The X chromosome is the most intensively studied chromosome in medical genetics; genes for over 300 diseases have been mapped to it. We will examine the genetic basis and significance of several X-linked mutations (e.g., the mutation proving the chromosome theory of inheritance and mutations that cause sex reversal). We will also discuss why men are more likely than women to display X-linked traits. This X-inequality between the sexes (XY males, XX females) raises an important biological question: how do males, with their single X chromosome per cell, and females, with two, balance their relative levels of X-linked gene expression? We will look at the different mechanisms by which X chromosome gene expression is equalized in mammals, flies, and worms and how these mechanisms can yield unusual phenotypes, such as calico cats, almost all of which are female. We will also discuss the evolutionary history of the X chromosome, considering questions such as: how did the X and Y chromosomes evolve from an ordinary pair of autosomes? what role do X-linked genes play in the male sterility of hybrid organisms, such as ligers, mules or zorses? and what can the X chromosome tell us about the speciation of humans? Throughout our discussions of the X chromosome we will use both recent and classic primary research papers to learn about this chromosome's fascinating biology.
The general format for the class will be that two papers will be read in detail before each class and the papers discussed in class. To facilitate the reading, a short 15-minute overview of the field and an introduction to the upcoming reading material will be presented at the end of the preceding session. During the last class, students will give a short oral presentation discussing a paper of their choice.
The goals of this course are to:
- Learn about the biology of the X chromosome from the perspectives of a medical geneticist and an evolutionary biologist
- Learn how to read and critique the primary scientific literature
- Develop an understanding of experimental approaches used in genetics
Grading in this course is pass/fail and will depend on attendance, participation and completion of class assignments.
||Introduction and course overview
||X chromosome genetics: Flies were first on the scene
||Medical diseases: Sex reversal and the X
||Dosage compensation I: X-inactivation in mammals
||Dosage compensation II: X-ceptions
||Dosage compensation III: Doubling and spreading
||Dosage compensation IV: Half and half in worms
||A highly conserved chromosome
||Gene content: A "sexy" X
||Divergence of the X and Y chromosomes
||Hybrids I: Haldane's rule
||Paper selection for oral presentation due
||Hybrids II: Are hybrids a step in the formulation of new species?