Normal vision in Drosophila requires NINAC, a class III myosin. Class III myosins are hybrid motor-signaling molecules, with an N-terminal kinase domain, highly conserved head and neck domains, and a class III-specific tail domain. In Drosophila rhabdomeres, NINAC interacts with actin filaments and with a PDZ scaffolding protein to organize the phototransduction machinery into a signaling complex. Recessive null mutations in Drosophila NINAC delay termination of the photoreceptor response and lead to progressive retinal degeneration. Here, we show that normal hearing in humans requires myosin IIIA, the human homolog of NINAC. In an extended Israeli family, nonsyndromic progressive hearing loss is caused by three different recessive, loss-of-function mutations in myosin IIIA. Of 18 affected relatives in Family N, 7 are homozygous and 11 are compound heterozygous for pairs of mutant alleles. Expression of mammalian myosin IIIA is highly restricted, with the strongest expression in retina and cochlea. The involvement of homologous class III myosins in both Drosophila vision and human hearing is an evolutionary link between these sensory systems.
It is now possible to assemble near-perfect bacterial genomes using Oxford Nanopore Technologies (ONT) long reads, but short-read polishing is usually required for perfection. However, the effect of short-read depth on polishing performance is not well understood. Here, we introduce Pypolca (with default and careful parameters) and Polypolish v0.6.0 (with a new careful parameter). We then show that: (1) all polishers other than Pypolca-careful, Polypolish-default and Polypolish-careful commonly introduce false-positive errors at low read depth; (2) most of the benefit of short-read polishing occurs by 25× depth; (3) Polypolish-careful almost never introduces false-positive errors at any depth; and (4) Pypolca-careful is the single most effective polisher. Overall, we recommend the following polishing strategies: Polypolish-careful alone when depth is very low (25×).