Molecular evolution of autophagy rate-limiting factor LAMP2 in placental mammals.

Molecular evolution of autophagy rate-limiting factor LAMP2 in placental mammals. Gene. 2019 Nov 07;:144231 Authors: Jalali Z, Parvaz N Abstract Autophagy is the cellular process of removal of misfolded or damaged macromolecules and organelles. Experimental studies have demonstrated autophagy as a major mechanism of lifespan extension in long-lived mammals such as bats and mole rat rodents. Moreover, the role of this biological process has been well documented in protection against age-associated diseases and viral infection. However, studies on the molecular adaptive changes of autophagy factors during evolution are scarce. Here, we conducted a bioinformatics study of the molecular evolution of the Lysosomal Associated Membrane Protein 2 (LAMP2), as a rate-limiting factor in the lysosomal degradation stage of autophagy (the communal step of two of autophagy types: macroautophagy and chaperone-mediated). Analyzing LAMP2 across placental mammals, our phylogenetic-based maximum likelihood analyses indicate that the majority of the coding sites undergo purifying selection. However, around 27% of sites display a relaxation of purifying constraints (average ω = 0.42128), among which, 14 particular sites undergo positive selection (ω>1). These sites are mostly located in the first luminal domain of LAMP2 (N-domain), with a hotspot region in the 135-144 codons interval. Therefore, the N-domain may account for the functional diversity a...
Source: Gene - Category: Genetics & Stem Cells Authors: Tags: Gene Source Type: research