Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas.

Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p < 5 × 10-8), of which two have not been previously reported in any ancestry group. We integrated fine-mapped loci with epigenomic and transcriptomic resources to highlight potential effector genes relevant to kidney physiology and disease, and reveal key regulatory elements and pathways involved in renal function and development. We demonstrate the varying but increased predictive power offered by a multi-ancestry polygenic score for eGFR and highlight the importance of population diversity in GWASs and multi-omics resources to enhance opportunities for clinical translation for all.

One Hundred Mitochondrial Genomes of Cicadas.

Mitochondrial genomes can provide valuable information on the biology and evolutionary histories of their host organisms. Here, we present and characterize the complete coding regions of 107 mitochondrial genomes (mitogenomes) of cicadas (Insecta: Hemiptera: Auchenorrhyncha: Cicadoidea), representing 31 genera, 61 species, and 83 populations. We show that all cicada mitogenomes retain the organization and gene contents thought to be ancestral in insects, with some variability among cicada clades in the length of a region between the genes nad2 and cox1, which encodes 3 tRNAs. Phylogenetic analyses using these mitogenomes recapitulate a recent 5-gene classification of cicadas into families and subfamilies, but also identify a species that falls outside of the established taxonomic framework. While protein-coding genes are under strong purifying selection, tests of relative evolutionary rates reveal significant variation in evolutionary rates across taxa, highlighting the dynamic nature of mitochondrial genome evolution in cicadas. These data will serve as a useful reference for future research into the systematics, ecology, and evolution of the superfamily Cicadoidea.

Changes in Endosymbiont Complexity Drive Host-Level Compensatory Adaptations in Cicadas.

For insects that depend on one or more bacterial endosymbionts for survival, it is critical that these bacteria are faithfully transmitted between insect generations. Cicadas harbor two essential bacterial endosymbionts, "Candidatus Sulcia muelleri" and "Candidatus Hodgkinia cicadicola." In some cicada species, Hodgkinia has fragmented into multiple distinct but interdependent cellular and genomic lineages that can differ in abundance by more than two orders of magnitude. This complexity presents a potential problem for the host cicada, because low-abundance but essential Hodgkinia lineages risk being lost during the symbiont transmission bottleneck from mother to egg. Here we show that all cicada eggs seem to receive the full complement of Hodgkinia lineages, and that in cicadas with more complex Hodgkinia this outcome is achieved by increasing the number of Hodgkinia cells transmitted by up to 6-fold. We further show that cicada species with varying Hodgkinia complexity do not visibly alter their transmission mechanism at the resolution of cell biological structures. Together these data suggest that a major cicada adaptation to changes in endosymbiont complexity is an increase in the number of Hodgkinia cells transmitted to each egg. We hypothesize that the requirement to increase the symbiont titer is one of the costs associated with Hodgkinia fragmentation.IMPORTANCE Sap-feeding insects critically rely on one or more bacteria or fungi to provide essential nutrients that are not available at sufficient levels in their diets. These microbes are passed between insect generations when the mother places a small packet of microbes into each of her eggs before it is laid. We have previously described an unusual lineage fragmentation process in a nutritional endosymbiotic bacterium of cicadas called Hodgkinia In some cicadas, a single Hodgkinia lineage has split into numerous related lineages, each performing a subset of original function and therefore each required for normal host function. Here we test how this splitting process affects symbiont transmission to eggs. We find that cicadas dramatically increase the titer of Hodgkinia cells passed to each egg in response to lineage fragmentation, and we hypothesize that this increase in bacterial cell count is one of the major costs associated with endosymbiont fragmentation.