MINERVA · MINERVA: A Haplotype Reconstruction Method for Indigenous South American Populations with Diverse Demographic Histories

In this project, MINERVA (Minimal Individual for Explaining Root Variation in Ancestry), I will craft novel computational methods to infer the minimal number of individuals required to explain the genetic diversity in populations that underwent severe bottlenecks. Through a scalable algorithmic framework, MINERVA will enable accurate autosomal haplotype reconstructions. We will leverage non-recombining genome regions, the Y chromosome, and mitochondrial DNA, inherited paternally and maternally, respectively. This will be reconciled with the autosomal phylogenies to provide a complete view of population dynamics across recombining and non-recombining genomic regions. With a new dataset from South America, this project will illuminate the genetic ancestry of the continent’s first settlers. While initially focusing on South America, MINERVA will be applicable to other bottlenecked populations, such as those in Greenland, the Faroe Islands, and Sardinia.Currently, no accurate methods exist for reconstructing ancestral haplotypes in bottlenecked populations, which is essential for determining whether high-frequency deleterious variants are inherited from ancestral haplotypes, arose through selection, are de novo mutations, or were introduced through admixture. This research will advance our understanding of population-specific genetic variation and improve the accuracy of genome-wide association studies and polygenic risk scores. Bottlenecked populations often have higher rates of genetic diseases, and our work will offer critical insights into their origins and transmission, with implications for genetic counseling and public health. During a secondment, I will collaborate with the Wuasikamas organization in southern Colombia to ensure cultural relevance. By engaging with the Inga community, I will present findings and foster a reciprocal exchange of knowledge, ensuring the research respects and benefits the communities involved.