Molecular ecology and population genetics of disease resistance in Red-winged Blackbirds (Agelaius phoeniceus)

    We have a great interest in the molecular ecology of major histocompatibility complex (Mhc) genes in Red-winged Blackbirds (Agelaius phoeniceus), a species made famous in part by studies conducted by Professor Emeritus Gordon Orians and Dr. Les Beletsky in our Department.  Mhc genes are the most polymorphic genes in vertebrates and are thought to be subject to diversity-enhancing types of natural selection such as balancing selection -- i.e., heterozygote advantage or rare-allele advantage.  Mhc genes are under such selection and are so diverse presumably because the parasites that are targets of Mhc genes are constantly changing, trying to escape   detection by the host immune system -- a true molecular coevolutionary arms race.  

    Red-winged Blackbirds are among the best studied songbirds in terms of behavioral ecology, parasite prevalence, mating systems and sexual selection.   Hence we hope to link variation in immunologically important genes, such as Mhc genes, and behavioral phenotypes in the field.  Mhc genes could affect the behavior of blackbirds in two main ways. First, Mhc genes could confer differential resistance to parasites, and hence could mediate mate choice in this species if parasites play an important role in such choice. Second, Mhc genes themselves have been suggested to influence mate choice in mice and humans. Perhaps female blackbirds can detect variations in Mhc genes, either directly or indirectly, and base their choice of mates in part on such intermale differences. Since obvious phenotypic targets of sexual selection have been difficult to find in red-winged blackbirds (the red epaulettes are more important in male-male competition for territories), maybe sexual selection is directed at "good genes" such as Mhc genes, or the immunological phenotypes conferred by such genes.

    To date we have focused more on the population genetics of Mhc genes in blackbirds, a necessary prerequisite to molecular ecological analysis.  Dan Garrigan in the lab has characterized variation across an exon-intron boundary in the first Mhc gene we cloned, called Agph-DAB1.  Examining variation across an exon-intron boundary is important for understanding the forces acting on Mhc genes. Because introns are largely neutral, examining the variation in such regions that are linked to coding regions that are under strong balancing selection can discriminate between a variety of hypotheses proposed to explain the high polymorphism of Mhc genes. If linked neutral regions such as introns are themselves highly diverse, then it is likely that strong linkage to the coding regions is responsible for the high intron polymorphism -- i.e., genetic hitchhiking.  On the other hand, if linked neutral regions are not polymorphic, then recombination could be prevalent in Mhc genes, causing the histories of coding and non-coding regions to become dissociated.  Whether or not recombination is an important force in Mhc genes of mammals has been a contentious issue, and we know nothing about recombination in avian Mhc genes.  Here is the abstract to Dan's paper on his research, which has currently been revised for publication in Molecular Biology and Evolution.

Polymorphism across an exon-intron boundary in an avian Mhc class II B gene

Daniel Garrigan and Scott V. Edwards

Twenty-three sequence haplotypes spanning the boundary of the second exon and intron of a Red-Winged Blackbird Mhc class II B gene, Agph-DAB1, are presented. The polymorphism of the exon segment is distributed in two divergent allelic lineages which appear to be maintained by balancing selection. The silent nucleotide diversity of the exon (p=0.101) is more than 5 times higher than that of the intron (p=0.018) and decays rapidly across the exon-intron boundary. Additionally, genealogical reconstruction indicates that divergence from a common ancestor in the exon sample is over 4 times greater than that of the intron. The intron sequences reveal a pattern of polymorphism which is characteristic of directional selection, rather than a pattern expected by linkage to a balanced polymorphism. These results suggest that the evolutionary histories of these two adjacent regions have been disassociated by recombination or gene conversion. The estimated population recombination parameter 4Nc=8.545 between the exon and intron is sufficiently high to explain the homogenization of intron sequences. Compatibility analyses estimate these events primarily occur from the exon-intron boundary to about 20-30 bases into the intron. Additionally, the observation that divergent exon alleles share identical intron sequence supports the conclusion of disassociation of exon and intron evolutionary histories by recombination.