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Accelerated recruitment of new brain development genes into the human genome - PubMed

Accelerated recruitment of new brain development genes into the human genome

Yong E Zhang et al. PLoS Biol. 2011 Oct.

Abstract

How the human brain evolved has attracted tremendous interests for decades. Motivated by case studies of primate-specific genes implicated in brain function, we examined whether or not the young genes, those emerging genome-wide in the lineages specific to the primates or rodents, showed distinct spatial and temporal patterns of transcription compared to old genes, which had existed before primate and rodent split. We found consistent patterns across different sources of expression data: there is a significantly larger proportion of young genes expressed in the fetal or infant brain of humans than in mouse, and more young genes in humans have expression biased toward early developing brains than old genes. Most of these young genes are expressed in the evolutionarily newest part of human brain, the neocortex. Remarkably, we also identified a number of human-specific genes which are expressed in the prefrontal cortex, which is implicated in complex cognitive behaviors. The young genes upregulated in the early developing human brain play diverse functional roles, with a significant enrichment of transcription factors. Genes originating from different mechanisms show a similar expression bias in the developing brain. Moreover, we found that the young genes upregulated in early brain development showed rapid protein evolution compared to old genes also expressed in the fetal brain. Strikingly, genes expressed in the neocortex arose soon after its morphological origin. These four lines of evidence suggest that positive selection for brain function may have contributed to the origination of young genes expressed in the developing brain. These data demonstrate a striking recruitment of new genes into the early development of the human brain.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. New gene contribution to various tissue transcriptomes.

The barplot shows the proportion of young genes out of all genes expressed in tissue or organ categories shared by UniGene human and mouse. For each category, mean and 2-fold standard deviation were plotted, which were generated with 100 bootstrapping replicates of background EST data. Only the brain shows a significant excess of new human genes based on Fisher's Exact Test (FET) with Bonferroni correction.

Figure 2
Figure 2. Proportion of young genes out of all genes differentially expressed between developmental stages.

For all samples, we compared two developmental stages, identified differentially expressed genes, and then plotted the proportion of young genes out of all early stage or late stage biased genes (Methods). The temporal lobe (one part of the neocortex) and cerebrum data compared fetal and adult brains, while the other three datasets compared infant with subsequent stages (Tables S1, S2).

Figure 3
Figure 3. Origination mechanisms of genes up-regulated in the adult and fetal brain.

Within each category, the barplot shows the proportion of genes up-regulated in adult brain and in fetal brain, respectively. Binomial test reveals that new genes originated by various mechanisms are significantly more frequently up-regulated in fetal brain (p<0.05).

Figure 4
Figure 4. Ka/Ks distribution across different group of genes.

All Ka/Ks values greater than 1 were trimmed to 1.

Figure 5
Figure 5. Proportion of genes differentially expressed between neocortex (or PFC) and the non-neocortical regions across different gene ages.

(A) The phylogenetic tree together with the branch assignments (0∼12) follows . 0 indicates the oldest gene group, i.e. genes shared by all vertebrates, and branches 8∼12 indicate primate-specific genes, with branch 12 the human-specific lineage. (B) Proportion of genes differentially expressed between neocortex and non-neocortical regions, detected by exon arrays for genes originating in each branch. The dashed line shows the trend fit based on the lowess function of R . (C) Genes with differential expression between PFC and non-neocortical control samples.

Figure 6
Figure 6. Origination of new genes up-regulated in PFC relative to non-neocortical regions after primate split.

Branches 9∼12 follows Figure 5A. The number of genes up-regulated in PFC and the total gene number represented by exon array are shown between “/”. For example, there are 280 human-specific genes, 54 out of which are up-regulated in PFC. In total, there are 198 (72+72+54) genes up-regulated in PFC (marked in RED), which originated along hominoid branches.

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