The Unique microRNAs of Naked Ape May Have Contributed to Human Evolution

    In the popular press, humans and other apes are said to share surprisingly large amounts of DNA. For example, human and chimpanzee DNA is supposed to be 98.8% the same. So why, readers are left to wonder, are humans so different from other apes? Readers usually have to content themselves with vague explanations—the small percentage of DNA that isn’t shared must be especially important, or some of the shared DNA is used differently from species to species.

    A more definite explanation has been suggested by scientists based at Spain’s Institute of Evolutionary Biology. These scientists, led by Yolanda Espinosa-Parrilla, Ph.D., looked at differences in gene expression within and across different apes—gorillas, orangutans, bonobos, chimpanzees, and humans. In particular, the scientists investigated post-transcriptional regulators of gene expression known as microRNAs (miRNAs).

    According to Dr. Espinosa-Parrilla and colleagues, human-specific variants of four miRNAs may have altered expression levels and gene targets compared to other apes. Also, these variants may be biologically relevant. That is, they may help explain what it is that makes us human.

    The Institute of Evolutionary Biology scientists published their findings April 22 in the open-access journal PLoS ONE, in an article entitled, “Functional Implications of Human-Specific Changes in Great Ape microRNAs.” The article described how the scientists analyzed the recent evolutionary history of 1595 human miRNAs by looking at their intra- and interspecies variation in great apes using high-coverage sequenced genomes of 82 individuals.

    “We explored the strength of purifying selection among microRNA regions and found that the seed and mature regions are under similar and stronger constraint than the precursor region,” wrote the article’s authors. “We further constructed a comprehensive catalogue of microRNA species-specific nucleotide substitutions among great apes and, for the first time, investigated the biological relevance that human-specific changes in microRNAs may have had in great ape evolution.”

    The authors found that changes in the sequence and length of four miRNAs may be specific to humans. Two were highly expressed in brain tissue and may exert effects on genes with neural functions, whereas the other two exhibits restricted expression patterns that the authors posited implied a role in development.

    “Expression and functional analyses of four microRNAs (miR-299-3p, miR-503-3p, miR-508-3p, and miR-541-3p) revealed that lineage-specific nucleotide substitutions and changes in the length of these microRNAs alter their expression as well as the repertoires of target genes and regulatory networks,” the authors detailed.

    The authors also found that “age” might matter; in an evolutionary sense, “younger” miRNAs had less sequence conservation, expression, and disease association, and were more isolated than “older” miRNAs.

    The authors suggest this study may aid in our understanding of how noncoding elements may have played a role in shaping some traits that ultimately became human specific. They also hope that it provides a framework to study the possible impact of these changes on recent human evolution.