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Article Abstract
Duplicated genes expanded in the human lineage likely contributed to brain evolution, yet challenges exist in their discovery due to sequence-assembly errors. We used a complete telomere-to-telomere genome sequence to identify 213 human-specific gene families. From these, 362 paralogs were found in all modern human genomes tested and brain transcriptomes, making them top candidates contributing to human-universal brain features. Choosing a subset of paralogs, long-read DNA sequencing of hundreds of modern humans revealed previously hidden signatures of selection, including for T cell marker CD8B. To understand roles in brain development, we generated zebrafish CRISPR "knockout" models of nine orthologs and introduced mRNA-encoding paralogs, effectively "humanizing" larvae. Our findings implicate two genes in possibly contributing to hallmark features of the human brain: GPR89B in dosage-mediated brain expansion and FRMPD2B in altered synapse signaling. Our holistic approach provides insights and a comprehensive resource for studying gene expansion drivers of human brain evolution.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12313184 | PMC |
| http://dx.doi.org/10.1016/j.cell.2025.06.037 | DOI Listing |
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