Dosage Compensation and Avian Diseases: Conservation Genomics of the Future

Dosage compensation is a mechanism ensuring equal levels of gene expression between the sexes in species having heteromorphic sex chromosomes. For example, the best studied vertebrate system is X chromosome inactivation (XCI), where traditional dogma states that in somatic cells of female mammals one X-chromosome is actively transcribed (Xa), while the other is completely inactive (Xi). This results in an equal level of X-linked gene expression when XX females and XY males are compared. However, more recent studies have demonstrated that certain genes on Xi may escape inactivation, where as many as 10 percent of all genes may be expressed during normal development.

All species of birds have sex chromosome heteromorphism, where males are ZZ and females ZW. In addition, not only do male songbirds sing while females do not, males have pronounced development of the telencephalon region of the brain, which is absent in females. This phenomenon is thought to result from the absence of dosage compensation of critical Z-linked genes, which would result in two-fold higher levels of gene expression in males compared with females. In addition, molecular studies in chickens and zebra finches have revealed that certain Z-linked genes appear to be dosage compensated while others do not.

The Genetics Division at CRES is currently constructing physical and linkage maps of the California condor genome to identify genes responsible for chondrodystrophy and other diseases. Fortuitous by-products of physical map construction are nucleotide sequences and chromosome locations of 30 Z-linked genes, the molecular reagents needed to assess dosage compensation in this species. Using microarrays and RNA-FISH, we will be able to measure Z to autosome expression ratios and whether one or both Z chromosomes were expressed. Also, by treating metaphase chromosomes from different species of birds with antibodies to conserved histone proteins that recognize inactive chromatin, we can examine differences in chromatin organization between ZZ males in different species.