Inter-population Differences in Retrogene Loss and Expression in Humans

Abstract

Gene retroposition leads to considerable genetic variation between individuals. Recent studies revealed the presence of at least 208 retroduplication variations (RDVs), a class of polymorphisms, in which a retrocopy is present or absent from individual genomes. Most of these RDVs resulted from recent retroduplications. In this study, we used the results of Phase 1 from the 1000 Genomes Project to investigate the variation in loss of ancestral (i.e. shared with other primates) retrocopies among different human populations. In addition, we examined retrocopy expression levels using RNA-Seq data derived from the Ilumina BodyMap project, as well as data from lymphoblastoid cell lines provided by the Geuvadis Consortium. We also developed a new approach to detect novel retrocopies absent from the reference human genome. We experimentally confirmed the existence of the detected retrocopies and determined their presence or absence in the human genomes of 17 different populations. Altogether, we were able to detect 193 RDVs; the majority resulted from retrocopy deletion. Most of these RDVs had not been previously reported. We experimentally confirmed the expression of 11 ancestral retrogenes that underwent deletion in certain individuals. The frequency of their deletion, with the exception of one retrogene, is very low. The expression, conservation and low rate of deletion of the remaining 10 retrocopies may suggest some functionality. Aside from the presence or absence of expressed retrocopies, we also searched for differences in retrocopy expression levels between populations, finding 9 retrogenes that undergo statistically significant differential expression.

Interpopulation differences of retroduplication variations (RDVs) in rice retrogenes and their phenotypic correlations

“…Compared with the research results of Kabza et al [25] on RDVs in humans, which was the only species that has been specifically studied for RDV in the past, some of our research results on RDV in rice were similar to those on human RDV. First, the frequency of most RDVs detected between populations was very low.…”

“…This supports results from previous studies, showing that many retrogenes have broad expression patterns [56] . Numerous studies have revealed a tendency for retrogenes to be expressed in the human testis [5] , [16] , [25] , which implies a certain connection between the male reproductive organs and retrogenes, and some mechanisms have been confirmed [33] , [57] , [58] . However, the set of analyzed retrogenes is relatively small and may not be fully representative.…”

“…First, the research of human RDV focuses on detecting the deletions of retrogenes relative to the reference genome, but since we cannot distinguish whether the reference genome or the genome being compared has insertion or deletion mutations [59] , in our work, we scanned insertions and deletions of retrogenes, which should be more comprehensive. Second, in the study of Kabza et al [25] , human RDV is defined as a fragment deletion of at least 100 bp, but this threshold was too high for the rice genome. Previous study has shown that the length of indel varies greatly, and there are also different length distributions among different species, the reason for this phenomenon may be that the directed evolution and molecular characteristics are different between human and rice genomes [60] , which implies that their retrotransposon activities are different, and it may also be related to their different selection and evolution histories [61] , [62] .…”

“…Three studies [6] , [23] , [24] have uncovered 208 RDVs in the human genome, two of which [23] , [24] facilitate the re-establishment of the phylogenetic tree of human populations, confirming the significance of RDV polymorphisms as genomic markers for a population’s history. Moreover, Kabza et al [25] developed a new approach to detect novel retrocopies not annotated in the reference genome and focused on identifying RDV caused by retrocopy deletion. By studying human genomes from 17 populations, they found 193 RDVs and analyzed their distribution among populations, which has important implications for studying human evolution and migration.…”

Mobile elements contribute to the uniqueness of human genome with 15,000 human-specific insertions and 14 Mbp sequence increase

“…Notably, our list does not cover the processed pseudogenes, which represent copies of mRNAs that were copied back into the genome as a side-product of L1-based transposition, 58 , 59 and the human-specific processed pseudogenes are likely to be in the order of hundreds based on the level of detected polymorphic levels. 60 , 61 …”