Abstract
Transposable elements (TEs) significantly contribute to shaping the diversity of the human genome, and lines of evidence suggest TEs as one of driving forces of human brain evolution. Existing computational approaches, including cross-species comparative genomics and population genetic modeling, can be adapted for the study of the role of TEs in evolution. In particular, diverse ancient and archaic human genome sequences are increasingly available, allowing reconstruction of past human migration events and holding the promise of identifying and tracking TEs among other evolutionarily important genetic variants at an unprecedented spatiotemporal resolution. However, highly degraded short DNA templates and other unique challenges presented by ancient human DNA call for major changes in current experimental and computational procedures to enable the identification of evolutionarily important TEs. Ancient human genomes are valuable resources for investigating TEs in the evolutionary context, and efforts to explore ancient human genomes will potentially provide a novel perspective on the genetic mechanism of human brain evolution and inspire a variety of technological and methodological advances. In this review, we summarize computational and experimental approaches that can be adapted to identify and validate evolutionarily important TEs, especially for human brain evolution. We also highlight strategies that leverage ancient genomic data and discuss unique challenges in ancient transposon genomics.
Highlights
The human brain is widely regarded as the substrate for a multitude of human-specific activities ranging from building complicated tools and using elaborate and abstract language to producing art, science, and distinct cultures [1, 2]
We focus on these active human retrotransposons due to their potential relevance to recent human evolution after human-Nonhuman primate (NHP) divergence, such as during the Neolithic period
Since most biological results were derived from studies of non-Transposable element (TE) genetic elements, we focus on methods that are adoptable to analyzing protein-coding TEs as well as assessing the expression level changes of host genes regulated by non-coding TEs
Summary
The human brain is widely regarded as the substrate for a multitude of human-specific activities ranging from building complicated tools and using elaborate and abstract language to producing art, science, and distinct cultures [1, 2]. Consistent with a previous study of the TE insertion rate in humans and chimpanzees [27], these studies provide further evidence that the human genome has the largest number of insertions from recently active TE families, and that a considerable portion of species-specific TE insertions localize to genic regions, indicating high potential for TEs to influence gene function during human evolution Another comparative genomic effort investigated both reference and polymorphic insertions and deletions of Alu and L1 in 83 deeply sequenced NHP genomes released by the Great Ape Genome Project [57] and 10 additional modern human genomes [58]. Methods to infer selection based on time-series AF data developed for aDNA [140, 141] can be applied to or adapted for TE-related natural selection scans These studies provide demographic information of ancient humans, such as population migration, mixture, and structure [132, 142], that is crucial for proper interpretation of AF changes and creation of population genetic models incorporating confounding factors such as genetic drift and gene flow. With recent technical advances in brain organoid models, long-read sequencing, and singlecell multi-omics approaches, we have an unprecedented opportunity to assess the effects of evolutionarily important TE insertions on human brain development and phenotypic divergence
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