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Memory is one of the highest cognitive functions that differentiates higher organisms from others because of its fundamental function to all learning and studying process. Recently, it was suggested that lactate works as a signaling molecule in neuronal plasticity system in long-term memory (LTM). These functions are reported only at mice so far, but it would be a universal phenomenon among various higher organisms. Because lactate is organic acid that is involved with energy production, it is of particular interest to know how memory associated genes including lactate-mediated neural plasticity (LMNP) genes get involved during evolution. I here set the purpose of my studies to understand the evolutionary origin and process of these memory-associated genes. Conducting an extensive literature survey, I collected a total of 302 genes of mice as memory associated genes. I, then, compared the number of genes orthologous to the 302 mice memory-associated genes among 11 representative organisms that I have chosen for the present study. As a result, I found that these memory-associated genes emerged at different time points during evolution, even before the emergence time of the organisms where memory function was reported. It suggests that memory function could be evolutionarily established gradually but not at once. Moreover, I examined 386 of LMNP-related genes of mice and other organisms to understand the evolutionary origin and processes of those genes that were identified by RNA-seq analyses (Margineanu et al., 2018). I found that the emergence times of LMNP genes were varied with genes, suggesting that the LMNP system may have been also formed gradually until its completion of the system around at the time of the common ancestor of vertebrates. Interestingly, I found that there are 13 genes overlap between the memory system and the LMNP system, indicating the critical role of those genes in connecting between both systems. From those studies, I conclude that the memory system and LMNP system has been formed by gradual participation of newly emerging genes during evolution, suggesting that the function of LMNP as a signaling molecule may be evolutionarily related to memory system by an unknown system that may exist to link both systems.

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