Somatic retrotransposition in the developing rhesus macaque brain

Area of Science:

• Genomics
• Evolutionary Biology
• Neuroscience

Background:

• LINE-1 (L1) retrotransposons are key drivers of human genome evolution and genetic diversity.
• Somatic L1 activity in primate brains is poorly understood, especially in nonhuman primates.
• L1 subfamilies have evolved in primate germlines since the divergence of apes and Old World monkeys.

Purpose of the Study:

• To investigate the potential for somatic L1 insertions in the brain of nonhuman primates.
• To explore L1 retrotransposition activity and somatic mosaicism in rhesus macaques.
• To understand the evolutionary implications of L1 mobility in primate brain development.

Main Methods:

• Single-cell whole-genome sequencing (scWGS) and retrotransposon capture sequencing (RC-seq) were applied to rhesus macaque hippocampal neurons.
• PCR validation was used to confirm somatic L1 insertions.
• Nanopore long-read methylome and RNA-seq analyses were performed.

Main Results:

• A somatic L1 insertion was detected and validated in approximately 7% of hippocampal neurons in one macaque.
• The insertion exhibited target site duplications and a short 5' transduction.
• The mobile donor L1 allele was located within the PRDM4 gene, which is expressed in neural stem cells.
• Analysis indicated young retrotransposon subfamily activation in early embryonic stages followed by repression in adult tissues.

Conclusions:

• This study provides the first evidence of L1-mediated somatic mosaicism in a nonhuman primate brain.
• It highlights the endogenous retrotransposition potential of macaque L1 elements.
• The findings suggest L1 mobility in the primate brain over the last 30 million years of evolution.