Abstract
BackgroundSmall insertions and deletions occur in humans at a lower rate compared to nucleotide changes, but evolve under more constraint than nucleotide changes. While the evolution of insertions and deletions have been investigated using ape outgroups, the now available genome of a Neandertal can shed light on the evolution of indels in more recent times.ResultsWe used the Neandertal genome together with several primate outgroup genomes to differentiate between human insertion/deletion changes that likely occurred before the split from Neandertals and those that likely arose later. Changes that pre-date the split from Neandertals show a smaller proportion of deletions than those that occurred later. The presence of a Neandertal-shared allele in Europeans or Asians but the absence in Africans was used to detect putatively introgressed indels in Europeans and Asians. A larger proportion of these variants reside in intergenic regions compared to other modern human variants, and some variants are linked to SNPs that have been associated with traits in modern humans.ConclusionsOur results are in agreement with earlier results that suggested that deletions evolve under more constraint than insertions. When considering Neandertal introgressed variants, we find some evidence that negative selection affected these variants more than other variants segregating in modern humans. Among introgressed variants we also identify indels that may influence the phenotype of their carriers. In particular an introgressed deletion associated with a decrease in the time to menarche may constitute an example of a former Neandertal-specific trait contributing to modern human phenotypic diversity.
Highlights
Small insertions and deletions occur in humans at a lower rate compared to nucleotide changes, but evolve under more constraint than nucleotide changes
When annotating indels with the class of genomic regions that is most likely to influence phenotype, we find that a significantly higher fraction of Neandertal-shared indels fall in intergenic regions compared to modern human specific indels (Fisher’s exact test; p = 1.77e-21; False Discovery Rate (FDR) adjusted p = 9.57e-21; odds ratio: 0.96) while modern human specific indels fall more often in intronic regions compared to shared indels, this difference is not significant after multiple testing correction (Fisher’s exact test; p = 0.04, FDR adjusted p = 0.08; odds ratio: 1.009)
We studied the differences between insertions and deletions using the Neandertal genome as an additional outgroup and found signals that suggest that deletions are more often deleterious than insertions
Summary
Small insertions and deletions occur in humans at a lower rate compared to nucleotide changes, but evolve under more constraint than nucleotide changes. High-coverage genome sequences were recently generated from ancient humans, including those from a Neandertal individual [3], a member of a group of close extinct relatives of all present-day humans. The sequence of the Neandertal genome provides a unique resource to study evolution since it can be used to sort sequence changes on the human lineage into those that likely occurred recently (i.e. those that are not shared with the Neandertal) and those that occurred earlier. Of. The study of the high-coverage Neandertal genome confirmed that modern humans outside of Africa trace a small percentage of their ancestry back to an admixture event with Neandertals [3]. Likely of small magnitude, the admixture event occurred sufficiently recent so that a large fraction (around 40%) of the Neandertal genome sequence segregates within present-day humans [4, 5]. Not all regions in the genome show an equal fraction of Neandertal ancestry, suggesting that a substantial fraction of the introgressed material was lost
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