Dual-targeted proteins tend to be more evolutionarily conserved.

In eukaryotic cells, identical proteins can be located in more than a single subcellular compartment, a phenomenon termed dual targeting. We hypothesized that dual-targeted proteins should be more evolutionary conserved than exclusive mitochondrial proteins, due to separate selective pressures administered by the different compartments to maintain the functions associated with the protein sequences. We employed codon usage bias, propensity for gene loss, phylogenetic relationships, conservation analysis at the DNA level, and gene expression, to test our hypothesis. Our findings indicate that, indeed, dual-targeted proteins are significantly more conserved than their exclusively targeted counterparts. We then used this trait of gene conservation, together with previously identified traits of dual-targeted proteins (such as protein net charge and mitochondrial targeting sequence strength) to 1) create, for the first time (due to addition of conservation parameters), a tool for the prediction of dual-targeted mitochondrial proteins based on protein and mRNA sequences, and 2) show that molecular mechanisms involving one versus two translation products are not correlated with specific dual-targeting parameters. Finally, we discuss what evolutionary pressure maintains protein dual targeting in eukaryotes and deduce, as we initially hypothesized, that it is the discrete functions of these proteins in the different subcellular compartments, regardless of their dual-targeting mechanism.

Body mass index and visual impairment in Israeli adolescents: A nationwide study.

BACKGROUND: Previous research on the association between body mass index (BMI) and visual impairment (VI) in youth has reported inconsistent findings. We aimed to investigate this association in a national cohort of Israeli adolescents. METHODS: This retrospective, population-based, cross-sectional study included 1 697 060 adolescents (56.4% men; mean age 17 years) who underwent mandatory pre-military service assessments from 1993 to 2017. BMI was classified based on the US age- and sex-matched percentiles. Unilateral or bilateral VI was classified as best-corrected visual acuity (BCVA) worse than 6/9 in either or both eyes, respectively. Sex-stratified regression models adjusted for sociodemographic variables were used to analyse the BMI-VI relationship. RESULTS: Overall, 17 871 (1.05%) and 5148 (0.30%) adolescents had unilateral and bilateral VI, respectively. Compared with high-normal BMI (50th to 85th percentile), adjusted odds ratios (ORs) for unilateral and bilateral VI gradually increased with higher BMI, reaching 1.33 (1.13-1.55) and 1.80 (1.37-2.35) in men with severe obesity, and 1.51 (1.24-1.84) and 1.52 (1.08-2.14) in women with severe obesity, respectively. Men with underweight also had increased ORs for unilateral and bilateral VI (1.23; 1.14-1.33 and 1.59; 1.37-1.84, respectively), a pattern not observed in women (0.96; 0.86-1.07 and 1.02; 0.83-1.25, respectively). Results were maintained when the outcome was restricted to mild VI, as well as in subgroups of adolescents with unimpaired health and those without moderate-to-severe myopia. CONCLUSIONS: Abnormal BMI, and particularly obesity, is associated with increased OR for VI in late adolescence.