Our research focuses on evolutionary and population genetics in humans and other primates.

We apply computational approaches to diverse genomics datasets to study the origin, evolution, and functional consequences of genetic variation. We are especially interested in structural variation and variation that influences infectious disease susceptibility, particularly malaria.

Comparative and population genomics across Plasmodium

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Recently, many Plasmodium genomes have been sequenced. These datasets include whole genome assemblies of 22 Plasmodium species and the Pf7 dataset from MalariaGEN, which includes Illumina shotgun sequencing of 16,203 P. falciparum isolates from around the world. We are applying a range of evolutionary approaches to study genome evolution, predict gene function, and identify signatures of natural selection in Plasmodium parasites.

Figure by Helena Hopson

Co-evolution of parasites and primates at the red blood cell interface

A crucial step in infection by malaria parasites is invasion of red blood cells, which is accomplished by a suite of interactions between parasite ligands and host receptors on the red blood cell surface. Many of the host proteins also determine blood groups. We study the evolution of blood group genes across primates, and merozoite ligands across Plasmodium. In humans, we are also investigating the co-evolutionary dynamics between the HbS (sickle) allele and P. falciparum variants that appear to overcome its protective effect on malarial disease.

Figure from Band et al. 2022

Structural variation and natural selection in paralogous gene clusters

Structural variants (SVs), which include copy number changes and more complex rearrangements of sequence, occur frequently throughout the genome and can have major functional effects. Yet SVs are more difficult to identify and genotype accurately and so are often overlooked. We are working to improve calling of SVs in repetitive regions and develop tests to detect positive or balancing selection in humans and other primates. We are also interested in the mutational mechanisms that give rise to these CNVs, which often involve mistakes by the recombination machinery in recognizing homology.

Figure by Ellen Leffler and George Busby

Malaria-protective variation around the world

Malaria-protective alleles show heterogeneity across the world as to where they are present and at what frequencies. This is due to the influence of a combination of evolutionary forces, including mutation (where the variants arose), selection (depending on where malaria has been present and how prevalent), and gene flow (how variants have spread between populations). We are interested in modeling these processes and evaluating genetic variation data for diverse populations to investigate how they have influenced the distribution of malaria-protective alleles. Currently, we are collaborating with Dr. Arwa Al Riyami at Sultan Qaboos University to investigate how genetic variation in the Omani population has been influenced by historical admixture and malaria-driven selection, especially at blood group loci.

Figure from Geography of Genetic Variants Browser

COLLABORATORS:

Dr. Sandrine Nsango
Centre Pasteur, Yaounde, Cameroon

Dr. Arwa Al-Riyami
Sultan Qaboos University, Muscat, Oman

Dr. Chaturong Putaporntip and Dr. Somchai Jongwutiwes
Chulalongkorn University, Bangkok, Thailand