Heather R.L. Lerner

Functional sites

Functional genetics and genomics for non-model organisms

In contrast to my phylogenetic work, which focuses on neutral DNA sequence variation (i.e. sequences not under selection), I am also interested in functional DNA sequences, especially the relationship between an organism's genome and its phenotype.

Until very recently, studies of non-model organisms have suffered from a lack of genomic information, limiting the ability of researchers to address functional genes and genomic variation. With the application of next-generation sequencing technologies, deeper understanding can be achieved with broader genomic sampling even for organisms currently lacking full-genome sequences. I have been using and developing new methods of targeting and tagging genomic regions for non-model organisms for next-generation sequencing. These methods allow me to quantify the diversity at functional genes, a powerful approach to the study of evolution with implications for species fitness and adaptive potential.

Harpy Eagle (Harpia harpyja) Genome and Raptor Comparative Genomics

Expanding on the conservation genetic work I conducted on harpy eagles as a graduate student, I am now sequencing the harpy eagle genome (in collaboration with Joshua Akey, U. of Wash. Dept. of Genome Sciences). Conservation programs aim to preserve this iconic bird and the primary rainforest in which it survives, but little is known about the genome of the harpy eagle. As part of the B10K project, genomic data has already been obtained (though not yet published) for the bald eagle, white-tailed eagle, peregrine falcon, barn owl and seriema. With comparative genome analysis of the harpy eagle and these other related birds, I aim to to identify genetic loci related to disease in raptors of conservation concern. The newly sequenced harpy genome will likely be used as material in an undergraduate Bioinformatics course at Earlham this spring. In May 2013, I will work with six Earlham undergraduate students for four weeks to perform raptor comparative genomics analyses of the students' own designs (funded as a Ford-Knight Undergraduate Research Project).

Avian MHC variability

Much attention to functional molecular markers has been focused on the major histocompatibility complex (Mhc), a family of highly variable genes that plays a crucial role in identifying pathogens. The effects of the Mhc are of increasing interest in natural avian populations as pathogens such as malaria and avian flu spread.

In the past, high levels of Mhc polymorphism have hindered sequence characterization, especially in avian species with high rates of gene duplication and pseudo-gene formation. Specifically, traditional methods of PCR, cloning and sequencing introduce the unavoidable possibility of heteroduplex chimaeras, particularly when amplifying a diversity of closely related alleles, such as in the Mhc. This bias leads to misidentification and an overestimate of alleles, which has plagued Mhc studies. I recently developed a new method for minimizing PCR and cloning bias in Mhc studies using an ancient DNA procedure for next-generation sequencing methods.

I have trained other scientists in this method and successfully applied it to four avian and mammalian study systems in collaborations involving both fresh tissue samples and older preserved museum skins. These projects address a variety of factors relating to the evolution of Mhc, allowing me to develop a deeper understanding of this important functional region. I am evaluating the effects of Mhc diversity on species persistence and evolution, as well as the intrinsic and extrinsic factors that influence Mhc diversity.

In mammals I am using two study systems to evaluate the effect of latitude (and related factors, such as pathogen load) on Mhc diversity as well as the relationship between specific Mhc alleles and communicable cancer. In avian species I am evaluating the influence of mate choice on Mhc evolution, and the relationship between Mhc variability and avian malaria susceptibility in several songbird taxa of conservation concern.