Selfish DNA and Fertility
The successful transmission of chromosomes to eggs and sperm is essential for human fertility and health. Mendel's first law describes how the two alleles in a heterozygous individual have equal chances of being transmitted to its progeny. Yet animals are continually challenged by selfish DNAs that subvert the process of chromosome segregation to gametes.
Daniel Barbash, Molecular Biology and Genetics, is determining the identity and mechanism whereby one type of selfish DNA, called meiotic drivers, are able to distort normal chromosome segregation into eggs. These selfish DNAs can reduce fertility and distort allele frequencies of host genes in populations.
Barbash is using the model organism Drosophila melanogaster (fruit flies), and novel methods to track the genotype and development state of individuals throughout the life cycle—from meiosis in their mothers through adulthood. Barbash is also applying both short-read and long-read sequencing technologies to identify candidate sequences responsible for drive. Following these mapping and sequencing approaches, experimental manipulation will be used to test and confirm the identity of the meiotic driver.
Evolutionary theory predicts that meiotic drive will vary in degree between populations. Barbash is investigating the magnitude of drive in both related and unrelated populations and then mapping and identifying major-effect modifier alleles. The research will provide an unprecedented level of information about the identity and mechanism of meiotic drivers that are segregating in natural populations. This will provide fundamental information about how animals, including humans, are able to maintain robust fertility.
NIH Award Number: 2R01GM074737-13A1