2-AIN-505, 2-AIN-251: Seminar in Bioinformatics (1), (3)
Winter 2024
Abstrakt

Xavi Guitart, David Porubsky, DongAhn Yoo, Max L. Dougherty, Philip C. Dishuck, Katherine M. Munson, Alexandra P. Lewis, Kendra Hoekzema, Jordan Knuth, Stephen Chang, Tomi Pastinen, Evan E. Eichler. Independent expansion, selection and hypervariability of the TBC1D3 gene family in humans. bioRxiv, 2024.

Download preprint: not available

Download from publisher: https://genome.cshlp.org/content/early/2024/08/05/gr.279299.124.abstract PubMed

Related web page: not available

Bibliography entry: BibTeX

Abstract:

TBC1D3 is a primate-specific gene family that has expanded in the human lineage 
and has been implicated in neuronal progenitor proliferation and expansion of the 
frontal cortex. The gene family and its expression have been challenging to 
investigate because it is embedded in high-identity and highly variable segmental 
duplications. We sequenced and assembled the gene family using long-read 
sequencing data from 34 humans and 11 nonhuman primate species. Our analysis 
shows that this particular gene family has independently duplicated in at least 
five primate lineages, and the duplicated loci are enriched at sites of 
large-scale chromosomal rearrangements on chromosome 17. We find that most humans 
vary along two TBC1D3 clusters where human haplotypes are highly variable in copy 
number, differing by as many as 20 copies, and structure (structural 
heterozygosity 90%). We also show evidence of positive selection, as well as a 
significant change in the predicted human TBC1D3 protein sequence. Lastly, we 
find that, despite multiple duplications, human TBC1D3 expression is limited to a 
subset of copies and, most notably, from a single paralog group: TBC1D3-CDKL. 
These observations may help explain why a gene potentially important in cortical 
development can be so variable in the human population.