Abstract
BackgroundAs the evolution of miRNA genes has been found to be one of the important factors in formation of the modern type of man, we performed a comparative analysis of the evolution of miRNA genes in two archaic hominines, Homo sapiens neanderthalensis and Homo sapiens denisova, and elucidated the expression of their target mRNAs in bain.ResultsA comparative analysis of the genomes of primates, including species in the genus Homo, identified a group of miRNA genes having fixed substitutions with important implications for the evolution of Homo sapiens neanderthalensis and Homo sapiens denisova. The mRNAs targeted by miRNAs with mutations specific for Homo sapiens denisova exhibited enhanced expression during postnatal brain development in modern humans. By contrast, the expression of mRNAs targeted by miRNAs bearing variations specific for Homo sapiens neanderthalensis was shown to be enhanced in prenatal brain development.ConclusionsOur results highlight the importance of changes in miRNA gene sequences in the course of Homo sapiens denisova and Homo sapiens neanderthalensis evolution. The genetic alterations of miRNAs regulating the spatiotemporal expression of multiple genes in the prenatal and postnatal brain may contribute to the progressive evolution of brain function, which is consistent with the observations of fine technical and typological properties of tools and decorative items reported from archaeological Denisovan sites. The data also suggest that differential spatial-temporal regulation of gene products promoted by the subspecies-specific mutations in the miRNA genes might have occurred in the brains of Homo sapiens denisova and Homo sapiens neanderthalensis, potentially contributing to the cultural differences between these two archaic hominines.
Highlights
As the evolution of miRNA genes has been found to be one of the important factors in formation of the modern type of man, we performed a comparative analysis of the evolution of miRNA genes in two archaic hominines, Homo sapiens neanderthalensis and Homo sapiens denisova, and elucidated the expression of their target mRNAs in bain
Using the selection procedure described in the Methods section (Selection of miRNA genes in H. s. d. and H. s. n. with no match in H. s. s.), we identified 1298 H. s. d. and 1329 H. s. n. pre-miRNAs perfectly matched to H. s. s. pre-miRNA gene sequences
We identified and selected for further study 106 H. s. d. and 102 H. s. n. diverged genes for pre-miRNA sequences, which were different from H. s. s. pre-miRNA genes by at least a single nucleotide
Summary
As the evolution of miRNA genes has been found to be one of the important factors in formation of the modern type of man, we performed a comparative analysis of the evolution of miRNA genes in two archaic hominines, Homo sapiens neanderthalensis and Homo sapiens denisova, and elucidated the expression of their target mRNAs in bain. S. genomes to reveal the structural and functional organization of microRNAs (miRNAs) as well as the mRNAs targeted by these miRNAs. Using improved versions of the H. s. S. genomes to reveal the structural and functional organization of microRNAs (miRNAs) as well as the mRNAs targeted by these miRNAs In both the Neanderthal and Denisovan genomes, we found miRNA genes with fixed substitutions in mature miRNAs and multiple substitutions in pre-miRNA regions involved in pre-miRNA processing. Our analysis of spatiotemporal gene expression in human tissues demonstrated that the miRNAs bearing new genetic variants fixed in the Denisovan genome regulated target mRNAs with the highest levels of expression in the postnatal human brain
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