Biology subjects

Popejoy, A. B.

Publications and source records attributed to Popejoy, A. B..

3 recordsLinked to original sources

bioRxiv2020

Genome-Wide Search for Candidate Drivers of Adaptation Reveals Genes Enriched for Shifts in Purifying Selection (SPurS)

An open question in comparative evolutionary genomics is whether or not certain loci are the primary drivers of divergence between taxonomic lineages or species groups. Alternatively, genetic drivers of species divergence may be evenly distributed across the genome. The increasing availability of genome sequences from diverse taxa has enabled the development of novel methods to address this question. Genomes of many highly diverged species may now be compared in order to tease apart genetic differences that drive adaptive or functional divergence, and genetic differences that are observed by chance and are not causally linked to traits that differ between species or lineages. In order to test the hypothesis that a particular subset of loci or genes is responsible for driving adaptive changes between mammals and non-mammals, we developed a novel comparative approach to identify sites that are highly conserved within lineages or species groups and diverge between them. Loci with a high concentration of these sites may be called Shifts in Purifying Selection (SPurS) because a change has occurred between two groups of species at some point in the past, and the shift is conserved (via purifying selection) over a long period of time. Evaluating 7484 orthologous gene copies from 76 vertebrate species, we developed an empirical distribution of SPurS across the genome between Synapsida (placental and non-placental mammals) and Sauropsida (birds, crocodilians, squamates, and turtles), and compared this distribution to the expected null distribution of SPurS using matched simulated data. We then identified a subset of genes that is enriched for SPurS, relative to the full set of genes and to their matched simulated alignments. These SPurS-enriched genes are thus likely candidate drivers of functional divergence or adaptation between the mammalian and non-mammalian species groups in our analysis. Investigators seeking to identify genetic drivers of inter-species evolution may find this method useful, and we provide a web-based software interface to facilitate its use.

evolutionary biology↗

bioRxiv2018

Standardized biogeographic grouping system for annotating populations in pharmacogenetic research

The varying frequencies of pharmacogenetic alleles between populations have important implications for the impact of these alleles in different populations. Current population grouping methods to communicate these patterns are insufficient as they are inconsistent and fail to reflect the global distribution of genetic variability. To facilitate and standardize the reporting of variability in pharmacogenetic allele frequencies, we present seven geographically-defined groups: American, Central/South Asian, East Asian, European, Near Eastern, Oceanian, and Sub-Saharan African, and two admixed groups: African American/Afro-Caribbean and Latino. These nine groups are defined by global autosomal genetic structure and based on data from large-scale sequencing initiatives. We recognize that broadly grouping global populations is an oversimplification of human diversity and does not capture complex social and cultural identity. However, these groups meet a key need in pharmacogenetics research by enabling consistent communication of the scale of variability in global allele frequencies and are now used by PharmGKB.

genetics↗

bioRxiv2018

The Clinical Imperative for Inclusivity: Race, Ethnicity, and Ancestry (REA) in Genomics

The Clinical Genome Resource (ClinGen) Ancestry and Diversity Working Group highlights the need to develop guidance on race, ethnicity, and ancestry (REA) data collection and use in clinical genomics. We present quantitative and qualitative evidence to characterize: 1) acquisition of REA data via clinical laboratory requisition forms, and 2) information disparity across populations in the Genome Aggregation Database (gnomAD) at clinically relevant sites as determined by variants in ClinVar. Our requisition form analysis showed substantial heterogeneity in clinical laboratory ascertainment of REA, as well as marked incongruity among terms used to define REA categories. There was also striking disparity across REA populations in the amount of information available about variants at clinically relevant sites in gnomAD. European ancestral populations constituted the majority of observations (55.8%), allele counts (59.7%), and private alleles (56.1%) in gnomAD at 550 loci with \"pathogenic\" and \"likely pathogenic\" expert-reviewed variants in ClinVar. Our findings highlight the importance of implementing and supporting programs to increase diversity in genome sequencing and clinical genomics, as well as measuring uncertainty around population-level datasets that are used in variant interpretation. Finally, we suggest the need for a standardized REA data collection framework to be developed and adopted across clinical genomics.

genomics↗