Joanna Malukiewicz, PhD

Research

Viral Disease Susceptibility in Platyrrhine Species and Hybrids

Anthropological genomics shows that hybrids may have a selective advantage to pathogenetic disease susceptibility. Given frequent hybridization in non-human primates, as well as recent viral pandemics, I am interested in the following question: How does the host genomic profile of anti-viral immune genes of primate species and their hybrids affect primate susceptibility to pathogenic disease? In platyrrhines (North, Central, and South American primates), addressing this question is complicated by our limited understanding of the immunogenetics of these primates. As my other work shows wide-spread hybridization in marmosets, I am using these primates to as models to characterize diversity and structure of key marmoset immunogenetic regions involved in immune response against viral infection. The major focus of this work is the major histocompatibility class I region of the marmoset genome. This regions is responsible for altering key immune cells ike T-cells and Natural-Killer cells about invading microbes like viruses. The MHC region (also known as HLA in humans) is notoriously difficult to study due to occurrence of gene duplications and repetitive sequences in the region. I am overcoming this challenge by combining targeted hybridization sequence capture with Oxford Nanopore long-read sequencing to sequence the MHC region. These genomic data are being combined with host genomic and virome data to develop generalized linear models to test the hypothesis that hybrids are less susceptible to viral disease.

Recent outbreaks of deadly Yellow Fever virus (YFV) in Brazil have shown that primate species differ in their susceptibility to this virus. To better understand why, I have begun two new collaborations with Drs. Ric del Rosario (Broad Institute) and Christian Roos (German Primate Center) using whole genome sequencing data from marmosets and howlers to look at genetic diversity and evolution of their immune genes. These two genera show dramatic differences in their YFV immune response. My future work in this area will include these two genera to investigate the role that hybridization and species-specific differences play in primate YFV susceptibility by integrating evolutionary genomics, viral metagenomics, and single-cell transcriptomics.

Black-tufted Marmoset (Callithrix penicillata) Reference Genome

Well-assembled and annotated high-quality genomes allow for more powerful comparative and population-level investigations of natural selection, structural variation, and complex genomic regions. In collaboration with Drs. Reed Cartwright (Arizona State University), Jeff French (University of Omaha-Nebraska), and Dr. Montserrat Torres-Oliva (University of Kiel), I am leading a project to generate an annotated de novo assembly of the C. penicillata genome (only C. jacchus assemblies are currently available and my work shows this is the sister lineage to C. penicillata). Custom annotation of the 2.6 GB C. penicillata assembly has resulted in 18,012 annotated protein coding genes and a 92.3% BUSCO score. Comparative genomics show the contraction of key immune genes within key immunogene families in C. penicillata. By using a combination of comparative and population genomics, I also have identified candidate selection genes and enriched pathways involved in insulin metabolism that may have allowed C. penicillata to adapt to extreme semi-arid biomes, as one of the few platyrrhines to do so.

Callitrichid Gut Microbiome

Mammalian captive dietary specialists like folivores are prone to gastrointestinal distress and primate dietary specialists suffer the greatest gut microbiome diversity losses in captivity compared to the wild. Marmosets represent another group of dietary specialists, exudivores that eat plant exudates (gums and resins), and I have lead the very first two projects looking at diversity of function of the gut microbiome of wild and captive marmosets within Brazil. Both projects looked at the gut microbiome of various marmoset species and hybrid types, but the first project used 16S rRNA gene sequencing and the second used shotgun whole genome sequencing. Wild Callithrix gut microbiomes were enriched for Bifidobacterium, which process the types of host-indigestible carbohydrates found in plant exudates eaten by marmosets. Captive marmoset guts were enriched for Enterobacteriaceae, a family containing pathogenic bacteria. Enterobacteriaceae seem to carry out most functional activities in captive host guts. More diverse bacterial taxa seem to perform gut functions in wild marmosets, with Bifidobacterium being important for carbohydrate metabolism. Captive marmosets showed gut microbiome composition aspects seen in human gastrointestinal diseases. Thus, this work showed that captivity may perturb the exudivore gut microbiome, which raises implications for captive exudivore welfare and calls for husbandry modifications. I have presented these results to several academic and biomedical groups as an invited speaker.

The shotgun whole genome sequencing project was carried out as a collaboration with Dr. Mirela D'arc (Federal University of Rio de Janeiro), representing an expansion of my work into other callitrichids - the highly endangered golden lion tamarin (GLT-Leontopithecus rosalia). The findings of this study are consistent with my previous work in showing that Bifidobacterium is an important component of the callitrichid gut microbiome. However, GTLs and marmosets were enriched for different species of Bifidobacterium. Additionally, the composition of GLT and marmoset gut microbiota is sensitive to host environmental factors. Overall, our data expand baseline gut microbiome data for callitrichids to allow for the development of new tools to improve their management and conservation.