TY - JOUR

T1 - A billion-year trend of amino acid substitutions in the mitochondrial genome

AU - Mikhailova, Alina A.

AU - Mikhailova, Alina G.

AU - Shamanskiy, Victor

AU - Ushakova, Kristina E.

AU - Galieva, Alima

AU - Lobanova, Valeria

AU - Timonina, Valeria

AU - Yurov, Valerian

AU - Olyanich, Maria

AU - Iliushchenko, Dmitry

AU - Smirnov, Aleksandr

AU - Mazunin, Ilya

AU - Polishchuk, Leonard

AU - Knorre, Dmitry G.

AU - Khrapko, Konstantin

AU - Гунбин, Константин Владимирович

AU - Fellay, Jacques

AU - Tanaka, Masashi

AU - Popadin, Konstantin

N1 - A billion-year trend of amino acid substitutions in the mitochondrial genome / Alina A. Mikhailova, Alina G. Mikhailova, Victor Shamanskiy, Kristina Ushakova, Alima Galieva, Valeria Lobanova, Valeria Timonina, Valerian Yurov, Maria Olyanich, Dmitry Iliushchenko, Aleksandr Smirnov, Ilya Mazunin, Leonard Polishchuk, Dmitry Knorre, Konstantin Khrapko, Konstantin Gunbin, Jacques Fellay, Masashi Tanaka, Konstantin Popadin // Abstracts from the 54th European Society of Human Genetics (ESHG) Conference: e-Posters // European Journal of Human Genetics. – 2022. – Vol. 30, No. S1. – P. 88-608. – DOI 10.1038/s41431-021-01026-1.

PY - 2022

Y1 - 2022

N2 - It has been shown that the rates of reciprocal amino acid substitutions in prokaryotic and eukaryotic organisms are not balanced leading to the long-term increase (i.e. ‘gainers’) or decrease (i.e. ‘losers’) in the frequency of some amino acids. However, the evolutionary driving forces establishing this trend are still unknown. Here, focusing on the strongly asymmetrical mutational spectrum of the mitochondrial genome (an excess of G to A and T to C, light chain notation), we predicted the preferential direction of amino acid substitutions from losers (LeuTT, Phe, Cys, Trp, Gly, and Val) to gainers (Pro, His, Gln, Asn, Lys, and Thr). Analyzing collections of nonsynonymous mtDNA mutations from human cancers (PCAWG), human pathogenic mutations (MitoMap database), human population polymorphisms, and mtDNA polymorphism from hundreds of vertebrate species, we observed that the vast majority of substitutions are indeed in the expected direction: from losers to gainers. Moreover, the observed bias is the most pronounced in datasets where mutagenesis is stronger than selection (cancer and human pathogenic mutations for example). Comparing the amino acid composition of mtDNA genes between orthologs of mitochondrial genes in alpha-proteobacteria, fungi, plants, invertebrates, and five classes of vertebrates, we observed a global billion-year trend: losers become rarer while gainers become more frequent among these taxa. These results are in line with the accumulation of slightly-deleterious variants (i.e. from losers to gainers) in mtDNA from the moment of endosymbiosis emergence till the current days due to genetic drift which becomes stronger from bacteria to vertebrates.

AB - It has been shown that the rates of reciprocal amino acid substitutions in prokaryotic and eukaryotic organisms are not balanced leading to the long-term increase (i.e. ‘gainers’) or decrease (i.e. ‘losers’) in the frequency of some amino acids. However, the evolutionary driving forces establishing this trend are still unknown. Here, focusing on the strongly asymmetrical mutational spectrum of the mitochondrial genome (an excess of G to A and T to C, light chain notation), we predicted the preferential direction of amino acid substitutions from losers (LeuTT, Phe, Cys, Trp, Gly, and Val) to gainers (Pro, His, Gln, Asn, Lys, and Thr). Analyzing collections of nonsynonymous mtDNA mutations from human cancers (PCAWG), human pathogenic mutations (MitoMap database), human population polymorphisms, and mtDNA polymorphism from hundreds of vertebrate species, we observed that the vast majority of substitutions are indeed in the expected direction: from losers to gainers. Moreover, the observed bias is the most pronounced in datasets where mutagenesis is stronger than selection (cancer and human pathogenic mutations for example). Comparing the amino acid composition of mtDNA genes between orthologs of mitochondrial genes in alpha-proteobacteria, fungi, plants, invertebrates, and five classes of vertebrates, we observed a global billion-year trend: losers become rarer while gainers become more frequent among these taxa. These results are in line with the accumulation of slightly-deleterious variants (i.e. from losers to gainers) in mtDNA from the moment of endosymbiosis emergence till the current days due to genetic drift which becomes stronger from bacteria to vertebrates.

UR - https://www.nature.com/articles/s41431-021-01026-1

U2 - 10.1038/s41431-021-01026-1

DO - 10.1038/s41431-021-01026-1

M3 - Conference article

VL - 30

SP - 535

JO - European journal of human genetics

JF - European journal of human genetics

SN - 1018-4813

IS - S1

M1 - P19.044.D

ER -