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The evolution and functional impact of human deletion variants shared with archaic hominin genomes.

Lin YL, Pavlidis P, Karakoc E, Ajay J, Gokcumen O - Mol. Biol. Evol. (2015)

Bottom Line: We found 17 exonic deletions that are shared with archaic hominin genomes, including those leading to three fusion transcripts.Our analyses suggest that these "exonic" deletion variants have evolved through different adaptive forces, including balancing and population-specific positive selection.Our findings reveal that genomic structural variants that are shared between humans and archaic hominin genomes are common among modern humans and can influence biomedically and evolutionarily important phenotypes.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, State University of New York at Buffalo, NY, US.

No MeSH data available.


Related in: MedlinePlus

Possible evolutionary scenarios explaining allele sharing (or lack thereof) between modern and archaic hominins. This figure shows possible evolutionary scenarios, in the form of cartoon phylogenetic trees, explaining the deletion polymorphisms across different lineages. Red color designates branches where the deletion was observed. The number shown under each tree is the number of polymorphic deletions corresponding to the observation. The red headers indicate the likely mechanisms, which were separated from each other by dotted lines, through which the allele sharing has evolved. The “human-specific deletion” scenario covers polymorphic deletions which are shared neither with Neandertal nor with Denisovan genomes. The “recurrent” scenario covers Neandertal- or Denisovan-shared human deletions, breakpoints of which vary among different lineages. The “Neandertal introgression” scenario indicates allele sharing due to Neandertal gene flow into non-African human populations. The “ancient genetic structure” scenario indicates deletions that were evolved in the Human–Neandertal ancestral population and have been maintained since then. The “primate incomplete lineage sorting” scenario indicates deletion polymorphisms that have potentially been maintained since before the Human–Chimpanzee divergence. The “hominid-specific insertion” scenario covers polymorphic deletions that are genotyped as deletions in chimpanzee and rhesus monkey, and show polymorphism in hominid genomes. This scenario represents likely novel sequences that evolved in the ancestral population of Neandertals and humans.
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msu405-F2: Possible evolutionary scenarios explaining allele sharing (or lack thereof) between modern and archaic hominins. This figure shows possible evolutionary scenarios, in the form of cartoon phylogenetic trees, explaining the deletion polymorphisms across different lineages. Red color designates branches where the deletion was observed. The number shown under each tree is the number of polymorphic deletions corresponding to the observation. The red headers indicate the likely mechanisms, which were separated from each other by dotted lines, through which the allele sharing has evolved. The “human-specific deletion” scenario covers polymorphic deletions which are shared neither with Neandertal nor with Denisovan genomes. The “recurrent” scenario covers Neandertal- or Denisovan-shared human deletions, breakpoints of which vary among different lineages. The “Neandertal introgression” scenario indicates allele sharing due to Neandertal gene flow into non-African human populations. The “ancient genetic structure” scenario indicates deletions that were evolved in the Human–Neandertal ancestral population and have been maintained since then. The “primate incomplete lineage sorting” scenario indicates deletion polymorphisms that have potentially been maintained since before the Human–Chimpanzee divergence. The “hominid-specific insertion” scenario covers polymorphic deletions that are genotyped as deletions in chimpanzee and rhesus monkey, and show polymorphism in hominid genomes. This scenario represents likely novel sequences that evolved in the ancestral population of Neandertals and humans.

Mentions: We considered several scenarios to explain the origins of polymorphic deletions among modern humans with respect to the Neandertal and Denisovan genomes (fig. 2). For the majority of human deletions, we found no evidence of allele sharing with archaic hominins. We will refer to these as “human-specific deletions.” It is important to note that our genotyping strategy in archaic hominin genomes is highly conservative and would not be able to pick up deletions that varied among archaic hominins at low frequencies. As such, the human-specific deletion data set may include several variants that are actually shared with other hominin genomes. First, we considered recurrence of the deletion polymorphisms in humans, Neandertals and/or Denisovans. Under this scenario, we expect that the breakpoints of the deletions differ between species. Indeed, we found evidence for 15 recurrent deletions in our manual inspection for different breakpoints (e.g., supplementary fig. S3D, Supplementary Material online), explaining approximately 3.5% of the deletions shared with archaic human genomes. We will refer to these deletions as “recurrent deletions.” With the high-quality Denisovan split-read support, we found no evidence for similar, but not exact breakpoints that we missed in our manual inspection. It is unlikely, but still possible for the deletions to be recurrent even if they share exact breakpoints. The 1KG deletion data set was compiled with accuracy as a main priority. As such, evolutionarily complex regions of the genome that show high levels of recurrence (e.g., Gokcumen et al. 2011) may have been underrepresented and further studies may uncover important recurrent deletions in these regions. Therefore, our estimate of 15 recurrent events is a lower bound for the recurrence of deletions among Human/Neandertal lineage.Fig. 2.


The evolution and functional impact of human deletion variants shared with archaic hominin genomes.

Lin YL, Pavlidis P, Karakoc E, Ajay J, Gokcumen O - Mol. Biol. Evol. (2015)

Possible evolutionary scenarios explaining allele sharing (or lack thereof) between modern and archaic hominins. This figure shows possible evolutionary scenarios, in the form of cartoon phylogenetic trees, explaining the deletion polymorphisms across different lineages. Red color designates branches where the deletion was observed. The number shown under each tree is the number of polymorphic deletions corresponding to the observation. The red headers indicate the likely mechanisms, which were separated from each other by dotted lines, through which the allele sharing has evolved. The “human-specific deletion” scenario covers polymorphic deletions which are shared neither with Neandertal nor with Denisovan genomes. The “recurrent” scenario covers Neandertal- or Denisovan-shared human deletions, breakpoints of which vary among different lineages. The “Neandertal introgression” scenario indicates allele sharing due to Neandertal gene flow into non-African human populations. The “ancient genetic structure” scenario indicates deletions that were evolved in the Human–Neandertal ancestral population and have been maintained since then. The “primate incomplete lineage sorting” scenario indicates deletion polymorphisms that have potentially been maintained since before the Human–Chimpanzee divergence. The “hominid-specific insertion” scenario covers polymorphic deletions that are genotyped as deletions in chimpanzee and rhesus monkey, and show polymorphism in hominid genomes. This scenario represents likely novel sequences that evolved in the ancestral population of Neandertals and humans.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4379406&req=5

msu405-F2: Possible evolutionary scenarios explaining allele sharing (or lack thereof) between modern and archaic hominins. This figure shows possible evolutionary scenarios, in the form of cartoon phylogenetic trees, explaining the deletion polymorphisms across different lineages. Red color designates branches where the deletion was observed. The number shown under each tree is the number of polymorphic deletions corresponding to the observation. The red headers indicate the likely mechanisms, which were separated from each other by dotted lines, through which the allele sharing has evolved. The “human-specific deletion” scenario covers polymorphic deletions which are shared neither with Neandertal nor with Denisovan genomes. The “recurrent” scenario covers Neandertal- or Denisovan-shared human deletions, breakpoints of which vary among different lineages. The “Neandertal introgression” scenario indicates allele sharing due to Neandertal gene flow into non-African human populations. The “ancient genetic structure” scenario indicates deletions that were evolved in the Human–Neandertal ancestral population and have been maintained since then. The “primate incomplete lineage sorting” scenario indicates deletion polymorphisms that have potentially been maintained since before the Human–Chimpanzee divergence. The “hominid-specific insertion” scenario covers polymorphic deletions that are genotyped as deletions in chimpanzee and rhesus monkey, and show polymorphism in hominid genomes. This scenario represents likely novel sequences that evolved in the ancestral population of Neandertals and humans.
Mentions: We considered several scenarios to explain the origins of polymorphic deletions among modern humans with respect to the Neandertal and Denisovan genomes (fig. 2). For the majority of human deletions, we found no evidence of allele sharing with archaic hominins. We will refer to these as “human-specific deletions.” It is important to note that our genotyping strategy in archaic hominin genomes is highly conservative and would not be able to pick up deletions that varied among archaic hominins at low frequencies. As such, the human-specific deletion data set may include several variants that are actually shared with other hominin genomes. First, we considered recurrence of the deletion polymorphisms in humans, Neandertals and/or Denisovans. Under this scenario, we expect that the breakpoints of the deletions differ between species. Indeed, we found evidence for 15 recurrent deletions in our manual inspection for different breakpoints (e.g., supplementary fig. S3D, Supplementary Material online), explaining approximately 3.5% of the deletions shared with archaic human genomes. We will refer to these deletions as “recurrent deletions.” With the high-quality Denisovan split-read support, we found no evidence for similar, but not exact breakpoints that we missed in our manual inspection. It is unlikely, but still possible for the deletions to be recurrent even if they share exact breakpoints. The 1KG deletion data set was compiled with accuracy as a main priority. As such, evolutionarily complex regions of the genome that show high levels of recurrence (e.g., Gokcumen et al. 2011) may have been underrepresented and further studies may uncover important recurrent deletions in these regions. Therefore, our estimate of 15 recurrent events is a lower bound for the recurrence of deletions among Human/Neandertal lineage.Fig. 2.

Bottom Line: We found 17 exonic deletions that are shared with archaic hominin genomes, including those leading to three fusion transcripts.Our analyses suggest that these "exonic" deletion variants have evolved through different adaptive forces, including balancing and population-specific positive selection.Our findings reveal that genomic structural variants that are shared between humans and archaic hominin genomes are common among modern humans and can influence biomedically and evolutionarily important phenotypes.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, State University of New York at Buffalo, NY, US.

No MeSH data available.


Related in: MedlinePlus