Chromosomal abnormalities such as differences in chromosome number (aneuploidy) are responsible for a many genetic diseases and disorders, and are the leading cause of miscarriage in humans. Nevertheless, throughout evolution striking changes have occurred in the number, size, and organization of chromosomes. This raises the question of how changes that are typically deleterious to individuals become incorporated into the evolutionary process. In particular, what molecular mechanisms change to facilitate this process? The stalk-eyed-fly, Teleopsis dalmanni, has undergone a recent and evolutionarily unusual sex chromosome "shift," in which the ancestral X is now an autosome, and one of the autosomes (2L in Drosophila) is now the X chromosome. This shift will have radically altered the dosage (copy number) of each X-linked and formerly X- linked gene in males of this species, so provides a unique opportunity to investigate how an organism can adapt to this type of change. The proposed research will investigate whether and how gene dosage has been compensated in this species.
The aims of the research are threefold.
The first aim will create a high-density linkage map that will allow assignment of chromosome orthology relative to Drosophila, allowing linkage group assignment of genomic contigs and identification of the chromosome orthologous to the X in D. melanogaster (now an autosome in Teleopsis). Once orthology is established, the second aim will compare male and female expression of genes on each linkage group. If dosage compensation is complete across the chromosome, expression of T. dalmanni X linked genes should on average be equal between the sexes relative to autosomal expression. Otherwise, expression will be lower on the male X. Expression of the ancestral X may or may not differ from the autosomes - it is possible that dosage compensating mechanisms present in Drosophila may still be hyper transcribing genes on the ancestral X, leading to over-expression of genes on this chromosome in males. Finally the third aim will determine whether the same proteins that compensate dosage in Drosophila are also functioning in T. dalmanni. If the same proteins are involved, compensated chromosomes in T. dalmanni should be bound specifically by antibodies made against these proteins. In the context of the X chromosome shift, this will address the question of whether compensation is achieved by co-opting an existing molecular pathway or through the evolution of a novel mechanism. The proposed research will deepen the understanding of how organisms adapt to chromosome-wide changes in gene dosage. This is relevant to general studies of chromosome function, including studies of disease-causing chromosome abnormalities.

Public Health Relevance

Changes in chromosome content often cause genetic diseases and disorders in individuals, but chromosomes nevertheless change throughout evolution. In the stalk-eyed fly, the X chromosome is evolutionarily novel, being descended from an autosome in other fly species. The proposed research will determine how these flies compensated to the shift in gene dosage that occurred when the new chromosome arose, providing insight into how organisms can cope with changes in chromosome number.

Agency
National Institute of Health (NIH)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM106619-02
Application #
8662560
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Reddy, Michael K
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Maryland College Park
Department
Biology
Type
Earth Sciences/Resources
DUNS #
City
College Park
State
MD
Country
United States
Zip Code
20742