Chromosomal rearrangements are key players in human health, having impacts in human fertility, cancers, and other diseases. Here we use an evolutionary approach to study chromosomal rearrangements and their potential to produce advantageous and detrimental cellular changes using Drosophila as a surrogate. We will sequence multiple populations of Drosophila from three different species and identify chromosomal rearrangements in each strain. We will determine whether genes in specific functional classes are more likely to be associated with rearrangements and whether specific genetic mechanisms influence their formation. We will use simulations and modeling to develop a framework to detect rearrangements that have been favored by selection. We will modify existing population genetic methods to correct for effects of demography, differential recombination, partial selective sweeps and other factors. We will then use RNA-sequencing to determine whether these selectively favored mutations are likely to be associated with changes in gene expression. In a second specific aim we will determine the extent to which rearrangements influence the results of artificial selection. We will identify rearrangements in selected and control strains, and compare the genetic background to wild-type strains of D. melanogaster.
This specific aim should explain whether genetic background correlates with selective outcomes and the extent to which pleiotropy limits evolution in nature. These methods will produce an in-depth view of chromosomal structural variation among species and will determine the ways in which they influence adaptation. Furthermore, we will establish new analytical methods that can more accurately identify selected regions, a result that can be applied to whole genome screens of selection in a large number of organisms. We will also link rearrangements to regulatory effects and will determine how this influences selective impacts.

Public Health Relevance

Abnormal chromosome structure in humans is associated with male infertility (1), spontaneous abortions (2), and several types of cancer (3). Many of these rearrangements cause changes in gene expression (4, 5), which can be involved in a wide range of diseases (6). Here, we examine chromosomal rearrangements from an evolutionary perspective, using Drosophila as a surrogate, to assess their propensity to produce detrimental and beneficial changes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM099377-03
Application #
8535795
Study Section
Special Emphasis Panel (ZRG1-F08-E (20))
Program Officer
Reddy, Michael K
Project Start
2011-09-01
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
3
Fiscal Year
2013
Total Cost
$52,190
Indirect Cost
Name
University of California Irvine
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Rogers, Rebekah L; Cridland, Julie M; Shao, Ling et al. (2014) Landscape of standing variation for tandem duplications in Drosophila yakuba and Drosophila simulans. Mol Biol Evol 31:1750-66