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Human-specific features of special gene expression and regulation in eight brain regions

ABSTRACT: Despite the substantial efforts made to compile the molecular maps of the human brain, they do not fully inform us of the features unique to humans. Yet, identification of these features might help us to understand both the evolution and nature of the human cognitive traits. Here, we approached this question by analyzing gene expression and H3K27ac chromatin modification data collected in eight brain regions of humans, chimpanzees, gorillas, gibbon and macaques. Integrated analysis of these data revealed existence of 1,851 human-specific transcriptome differences affecting one or multiple brain regions, in contrast to 240 chimpanzee-specific ones. More than a half of these differences represented elevated expression in human hippocampus, while the rest affected microglial functions in neocortex. Analysis of predicted regulatory interactions driving these differences revealed role of transcription factors in species-specific transcriptome changes, while epigenetic modifications were linked to spatial expression differences conserved across species.

ORGANISM(S): Gorilla gorilla Hylobates lar Pan troglodytes Homo sapiens

PROVIDER: GSE100796 | GEO | 2018/06/04

REPOSITORIES: GEO

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Project description:Although a large proportion of human transcription occurs outside the boundaries of known genes, the functional significance of this transcription remains unknown. We have compared the expression patterns of known genes as well as intergenic transcripts within the ENCODE regions between humans and chimpanzees in brain, heart, testis and lymphoblastoid cell lines. We find that intergenic transcripts show patterns of tissue-specific conservation of their expression which are comparable to exonic transcripts of known genes. This suggests that intergenic transcripts are subject to functional constraints that restrict their rate of evolutionary change as well as putative positive selection to an extent comparable to that of classical protein-coding genes. In brain and testis, we find that part of this intergenic transcription is caused by wide-spread use of alternative promoters. Further, we find that about half of the expression differences between humans and chimpanzees are due to intergenic transcripts. In order to transfer genetic information encoded in the genomic sequence of an organism into functional features, the genomic sequence must be transcribed. According to the current genome annotation, the human genome produces transcripts from 20,00025,000 protein-coding genes and a smaller number of non-coding genes. Recently, the introduction of tiling arrays that enable the measurement of transcription regardless of previous annotation challenged this view by providing evidence that a large proportion of transcription occurs outside of annotated genes. It has been suggested that these transcripts represent previously unidentified functional RNAs as well as extensions of known genes. However, their lack of conservation between species on the DNA sequence level raises questions about their functionality. In this study we assess the functionality of these novel transcripts by testing the extent to which their expression is conserved between humans and chimpanzees in different tissues. Surprisingly, we find the expression of known and novel transcripts to be conserved to the same relative extent when different tissues are compared. This suggests that both known and novel transcripts are equally affected by adaptive and stabilizing selection in different tissues during human and chimpanzee evolution. Further, in terms of absolute numbers, about half of the expression differences between humans and chimpanzees in any given tissue are due to intergenic transcripts.

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Human-specific features of special gene expression and regulation in eight brain regions

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