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Evidence of a Conserved Molecular Response to Selection for Increased Brain Size in Primates.

ABSTRACT: The adaptive significance of human brain evolution has been frequently studied through comparisons with other primates. However, the evolution of increased brain size is not restricted to the human lineage but is a general characteristic of primate evolution. Whether or not these independent episodes of increased brain size share a common genetic basis is unclear. We sequenced and de novo assembled the transcriptome from the neocortical tissue of the most highly encephalized nonhuman primate, the tufted capuchin monkey (Cebus apella). Using this novel data set, we conducted a genome-wide analysis of orthologous brain-expressed protein coding genes to identify evidence of conserved gene-phenotype associations and species-specific adaptations during three independent episodes of brain size increase. We identify a greater number of genes associated with either total brain mass or relative brain size across these six species than show species-specific accelerated rates of evolution in individual large-brained lineages. We test the robustness of these associations in an expanded data set of 13 species, through permutation tests and by analyzing how genome-wide patterns of substitution co-vary with brain size. Many of the genes targeted by selection during brain expansion have glutamatergic functions or roles in cell cycle dynamics. We also identify accelerated evolution in a number of individual capuchin genes whose human orthologs are associated with human neuropsychiatric disorders. These findings demonstrate the value of phenotypically informed genome analyses, and suggest at least some aspects of human brain evolution have occurred through conserved gene-phenotype associations. Understanding these commonalities is essential for distinguishing human-specific selection events from general trends in brain evolution.

SUBMITTER: Boddy AM

PROVIDER: S-EPMC5381557 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Evidence of a Conserved Molecular Response to Selection for Increased Brain Size in Primates.

Boddy Amy M AM Harrison Peter W PW Montgomery Stephen H SH Caravas Jason A JA Raghanti Mary Ann MA Phillips Kimberley A KA Mundy Nicholas I NI Wildman Derek E DE

Genome biology and evolution 20170301 3

The adaptive significance of human brain evolution has been frequently studied through comparisons with other primates. However, the evolution of increased brain size is not restricted to the human lineage but is a general characteristic of primate evolution. Whether or not these independent episodes of increased brain size share a common genetic basis is unclear. We sequenced and de novo assembled the transcriptome from the neocortical tissue of the most highly encephalized nonhuman primate, th ...[more]

PMID: 28391320

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Project description:BackgroundTranscribed pseudogenes are copies of protein-coding genes that have accumulated indicators of coding-sequence decay (such as frameshifts and premature stop codons), but nonetheless remain transcribed. Recent experimental evidence indicates that transcribed pseudogenes may regulate the expression of homologous genes, through antisense interference, or generation of small interfering RNAs (siRNAs). Here, we assessed the genomic evidence for such transcribed pseudogenes of potential functional importance, in the human genome. The most obvious indicators of such functional importance are significant evidence of conservation and selection pressure.ResultsA variety of pseudogene annotations from multiple sources were pooled and filtered to obtain a subset of sequences that have significant mid-sequence disablements (frameshifts and premature stop codons), and that have clear evidence of full-length mRNA transcription. We found 1750 such transcribed pseudogene annotations (TPAs) in the human genome (corresponding to approximately 11.5% of human pseudogene annotations). We checked for syntenic conservation of TPAs in other mammals (rhesus monkey, mouse, rat, dog and cow). About half of the human TPAs are conserved in rhesus monkey, but strikingly, very few in mouse (approximately 3%). The TPAs conserved in rhesus monkey show evidence of selection pressure (relative to surrounding intergenic DNA) on: (i) their GC content, and (ii) their rate of nucleotide substitution. This is in spite of distributions of Ka/Ks (ratios of non-synonymous to synonymous substitution rates), congruent with a lack of protein-coding ability. Furthermore, we have identified 68 human TPAs that are syntenically conserved in at least two other mammals. Interestingly, we observe three TPA sequences conserved in dog that have intermediate character (i.e., evidence of both protein-coding ability and pseudogenicity), and discuss the implications of this.ConclusionThrough evolutionary analysis, we have identified candidate sequences for functional human transcribed pseudogenes, and have pinpointed 68 strong candidates for further investigation as potentially functional transcribed pseudogenes across multiple mammal species.

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Evidence of a Conserved Molecular Response to Selection for Increased Brain Size in Primates.

Publications

Evidence of a Conserved Molecular Response to Selection for Increased Brain Size in Primates.

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