Love, K. | Search bioRxiv

bioRxiv2024

Genomic diversity of the African malaria vector Anopheles funestus

Anopheles funestus s.s. is a formidable human malaria vector across sub-Saharan Africa. To understand how the species is evolving, especially in response to malaria vector control, we sequenced 656 modern specimens (collected 2014-2018) and 45 historic specimens (collected 1927-1967) from 16 African countries. We find high levels of genetic variation with clear and stable continental patterns. Six segregating inversions might be involved in adaptation of local ecotypes. Strong recent signals of selection centred on canonical insecticide resistance genes are shared by multiple populations. A promising gene drive target in An. gambiae is highly conserved in An. funestus. This work represents a significant advance in our understanding of the genetic diversity and population structure of An. funestus and will enable smarter targeted malaria control.

genomics↗

bioRxiv2023

Transcript errors generate a continuous stream of amyloid and prion-like proteins in human cells

Aging is characterized by the accumulation of amyloid and prion-like proteins. However, the molecular mechanisms by which these proteins arise remain unclear. Here, we demonstrate that transcript errors generate amyloid and prion-like proteins in a wide variety of human cell types, including stem cells, brain organoids, and fully differentiated neurons. Intriguingly, some of these proteins are identical to proteins previously implicated in familial cases of amyloid diseases, raising the possibility that both familial and non-familial cases are caused by identical mutant proteins. However, transcript errors also generate amyloid proteins that have not been observed before, suggesting that aging cells are exposed to a second class of pathogenic proteins we are currently unaware of. Finally, we show that transcript errors are readily generated by DNA damage, a hallmark of human aging and a staple of multiple proteotoxic diseases, including Alzheimers disease. Together, these observations greatly expand our understanding of mutagenesis in human aging and disease and suggest a new mechanism by which amyloid diseases can develop.

molecular biology↗