Male birds display remarkable variation in plumage coloration, and females assess these differences when selecting mates. The rationale for such mate choice is that ornamentation is correlated with genetic quality so that, by choosing colorful males, females obtain good genes for their offspring. Genes contributing to greater disease resistance are quintessential in the natural world because pathogens greatly affect their hosts' reproduction and survival. As a result, "resistance" genes have often been assumed to be the good genes associated with bright coloration. The hypothesis of plumage coloration signaling good genes will be tested first by determining which genes are switched on or off when House Finches are infected with the bacterial pathogen, Mycoplasma gallicepticum. Gene expression will be determined using tools called microarrays that can accurately quantify the increase or decrease in expression of thousands of genes simultaneously. Gene expression patterns will be compared between brightly colored and drably colored male House finches. If the Good Genes Hypothesis is correct, brighter males should show different gene expression profiles than drabber ones. Furthermore, the turning on of specific genes known to play a role in disease resistance will help determine whether plumage coloration is associated with specific good genes. This research is important because it improves understanding of the evolutionary processes that lead to the evolution of disease resistance. Understanding all facets of disease resistance is crucial for predicting and responding to the threats of emerging infectious diseases in wildlife, domestic animals, and humans.
The House Finch-Mycoplasma gallisepticum (MG) host-pathogen interaction is an excellent model for a variety of questions in evolutionary biology and sexual selection. MG is usually found in poultry but in 1994 field scientists detected it in populations of House Finches introduced in the 1940s to the eastern US. The disease spread rapidly throughout house finches in the eastern US and is now found in all US states except a few in the southwest. Using a combination of genomic comparisons across geography, historical insights of museum specimens and experimental infections, we are reconstructing the history of spread and co-evolutionary interactions between host and pathogen. This project had three goals: 1) to understand the gene expression response of House Finches to the bacterial pathogen Mycoplasma gallisepticum; 2) to identify specific genes and regulatory sequence variations that might underlie gene expression response to MG infection; and finally 3) to determine these expression responses to MG infection correlated with plumage brightness. During the duration of the grant, we accomplished goals 1 and 2; goal 3 is still being pursued under other funding. In a key paper we published in the journal Proceedings of the National Academy of Sciences of the United States of America (Bonneaud et al. 2011 PNAS 108: 7866-7871), we showed that House Finches from populations such as Arizona that had never been exposed to MG in nature showed a dramatically different gene expression response than did birds from Alabama, where populations had been exposed to MG in nature for over a decade (Fig. 1). Moreover, the pattern of gene expression response to infection in Alabama birds sampled in 2007, 13 years after initial exposure to MG in the wild, was substantially different from that seen in an earlier study examining gene expression response in Alabama birds sampled in 2001. Intriguingly, the response seen in Arizona birds sampled in 2007 was very similar to that seen in the earlier study among Alabama birds sampled in 2001. The data suggests that the gene expression response of the Alabama population has changed in the time interval between the two studies, and that the Arizona population is recapitulating the response of recently exposed populations such as Alabama in 2001. This study provides a rare glimpse of the changes in gene expression response to pathogens that can occur over a short interval, and provides insight into how populations, including humans, can adapt to a rapidly evolving pathogen. Such studies are difficult or impossible to perform in humans because of the inability to conduct infection experiments in humans. Thus birds provide a useful model for how humans might respond to pathogen infection and how this response might change over time. In our recent work we have been able to accomplish goal #2, which consisted of identifying specific genes and regulatory sequence variations that might underlie gene expression response to MG infection. We used a draft genome of the house finch to find the sequences corresponding to regulatory regions of three House Finch genes that showed strong differential expression upon infection with MG. The sequence variations in the promoter regions of one of these genes, Heat-shock protein 90a, showed substantial variation. Moreover, the pattern of polymorphism at two single-nucleotide polymorphisms (SNPs) in this promoter correlated with the pathogen load of MG displayed by individual birds (Fig. 2). Although we have not demonstrated a causal relationship between these SNPs and pathogen load in House Finches, our results do suggest that promoter variation could be important for adaptation of House Finches to evolving MG in the wild. Preliminary data on goal three suggests that plumage brightness could be an important indicator for the pattern of gene expression response to infection in these birds. Specifically, we have seen that birds that are more yellow, and that have not acquired sufficient careotenoids to display the bright red plumage favored by females of this species, exhibit a gene expression response similar to that of House Finch populations that are naïve to the pathogen in nature (such Arizona in 2007 and, less so, Alabama in 2001). These results suggest that red plumage may be an indicator of immunogenetically superior birds. We aim to complete this goal and further test this hypothesis pending additional funding. Overall this project provided a useful window into how populations of vertebrates, such as humans, might adapt to an evolving pathogen such as Mycoplasma. Our results on the speed and type of adaptations in House Finches might be useful for predicting the human response to pathogens in the future, and the phenotypic and genetic correlates of that response. The broader impacts included training of postdoctoral and graduate students, as well as undergraduates and a high-school teacher.
