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Transcriptome Analyses Implicate Recently Evolved Genes in Human Brain Evolution

NEW YORK (GenomeWeb News) – Early brain development in humans involves the expression of a larger proportion of recently evolved genes than does brain development in mice, according to a new study in PLoS Biology, suggesting evolutionarily young genes may have subjected to positive selection during human brain evolution.

University of Chicago researchers used gene expression data on various mouse and human tissues to explore the timing and tissue-specificity of expression for evolutionarily "older" and "younger" genes. When they looked at young genes found exclusively within the primate or rodent lineages, for example, they found that a larger proportion of recently evolved genes are expressed during human brain development than during the development of rodent brains.

Such patterns are especially pronounced in the recently evolved neocortex region and the prefrontal cortex, a brain area that's thought to contribute to complex cognition.

"We're not talking about one or two genes, we're talking about many genes," University of Chicago ecology and evolution researcher Manyuan Long, the study's senior author, said in a statement. "This is a process that is continually moving and changing our brain."

The findings stemmed from initial analyses of gene expression data from the UniGene database, in which the researchers explored the expression of evolutionarily old and young genes in various tissues at different stages of development in humans and mice.

The analysis hinted that a greater proportion of newer genes are expressed in the human brain than in the brains of mice. For instance, they found that around three percent of genes expressed in the human brain were primate-specific genes, whereas rodent-specific genes made up about 1.5 percent of the genes expressed in mouse brain samples.

When they looked at additional data on fetal brain samples, the team found a similar pattern: 175 of the primate-specific genes were expressed in the human UniGene samples, compared to 51 of the primate-specific genes expressed in developing mouse brains.
By comparing data on tissue from more than a dozen regions of the fetal brain, meanwhile, the team found clues that evolutionarily younger genes were prone to expression in the neocortex of the human brain during development.

As such, the partiality toward primate-specific gene expression in the human brain appeared to be a characteristic of early brain development, the researchers reported, primarily occurring in parts of the human brain that evolved relatively recently.

"The primate-specific genes act before birth, even when a human embryo doesn't look very different from a mouse embryo," co-author Patrick Landback, a graduate student at the University of Chicago, said in a statement. "But the actual differences are laid out early."

Based on their analyses of mechanisms that appear to have produced the primate-specific genes involved, the evolutionary patterns of their protein products, and the predicted timing of evolution in relation to the advent of new brain regions in humans, the researchers speculated that brain evolution may have placed positive selection pressure on recently evolved genes, hastening their recruitment to the genome.

Nevertheless, they noted that studies will be needed to test this hypothesis further and to determine what functional roles some of the candidate genes might have in human brain function or evolution.

"We don't know if this observation has any causation biologically," Long said, "and there is a long way to go from here, but this correlation can predict some future work to do."

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