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Conservation, evolution, and regulation of splicing during prefrontal cortex development in humans, chimpanzees, and macaques.

ABSTRACT: Changes in splicing are known to affect the function and regulation of genes. We analyzed splicing events that take place during the postnatal development of the prefrontal cortex in humans, chimpanzees, and rhesus macaques based on data obtained from 168 individuals. Our study revealed that among the 38,822 quantified alternative exons, 15% are differentially spliced among species, and more than 6% splice differently at different ages. Mutations in splicing acceptor and/or donor sites might explain more than 14% of all splicing differences among species and up to 64% of high-amplitude differences. A reconstructed trans-regulatory network containing 21 RNA-binding proteins explains a further 4% of splicing variations within species. While most age-dependent splicing patterns are conserved among the three species, developmental changes in intron retention are substantially more pronounced in humans.

SUBMITTER: Mazin PV

PROVIDER: S-EPMC5855957 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Conservation, evolution, and regulation of splicing during prefrontal cortex development in humans, chimpanzees, and macaques.

Mazin Pavel V PV Jiang Xi X Fu Ning N Han Dingding D Guo Meng M Gelfand Mikhail S MS Khaitovich Philipp P

RNA (New York, N.Y.) 20180123 4

Changes in splicing are known to affect the function and regulation of genes. We analyzed splicing events that take place during the postnatal development of the prefrontal cortex in humans, chimpanzees, and rhesus macaques based on data obtained from 168 individuals. Our study revealed that among the 38,822 quantified alternative exons, 15% are differentially spliced among species, and more than 6% splice differently at different ages. Mutations in splicing acceptor and/or donor sites might exp ...[more]

PMID: 29363555

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Project description:There is evidence for enlargement of association cortex in humans compared to other primate species. Expansion of temporal association cortex appears to have displaced extrastriate cortex posteriorly and inferiorly in humans compared to macaques. However, the details of the organization of these recently expanded areas are still being uncovered. Here, we used diffusion tractography to examine the organization of extrastriate and temporal association cortex in chimpanzees, humans, and macaques. Our goal was to characterize the organization of visual and auditory association areas with respect to their corresponding primary areas (primary visual cortex and auditory core) in humans and chimpanzees. We report three results: (1) Humans, chimpanzees, and macaques show expected retinotopic organization of primary visual cortex (V1) connectivity to V2 and to areas immediately anterior to V2; (2) In contrast to macaques, chimpanzee and human V1 shows apparent connectivity with lateral, inferior, and anterior temporal regions, beyond the retinotopically organized extrastriate areas; (3) Also in contrast to macaques, chimpanzee and human auditory core shows apparent connectivity with temporal association areas, with some important differences between humans and chimpanzees. Diffusion tractography reconstructs diffusion patterns that reflect white matter organization, but does not definitively represent direct anatomical connectivity. Therefore, it is important to recognize that our findings are suggestive of species differences in long-distance white matter organization rather than demonstrations of direct connections. Our data support the conclusion that expansion of temporal association cortex, and the resulting posterior displacement of extrastriate cortex, occurred in the human lineage after its separation from the chimpanzee lineage. It is possible, however, that some expansion of the temporal lobe occurred prior to the separation of humans and chimpanzees, reflected in the reorganization of long white matter tracts in the temporal lobe that connect occipital areas to the fusiform gyrus, middle temporal gyrus, and anterior temporal lobe.

Dataset Information

Conservation, evolution, and regulation of splicing during prefrontal cortex development in humans, chimpanzees, and macaques.

Publications

Conservation, evolution, and regulation of splicing during prefrontal cortex development in humans, chimpanzees, and macaques.

Similar Datasets

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