View in EDS HTML Full Text PDF Full Text

A global map for introgressed structural variation and selection in humans.

Saved in:
Bibliographic Details
Title: A global map for introgressed structural variation and selection in humans.
Authors: Hsieh, PingHsun (AUTHOR), Soisangwan, Natthapon (AUTHOR), Gordon, David S. (AUTHOR), Javidh, Athef (AUTHOR), Harvey, William T. (AUTHOR), Porubsky, David (AUTHOR), Hoekzema, Kendra (AUTHOR), Baker, Carl (AUTHOR), Munson, Katherine M. (AUTHOR), Kinipi, Christopher (AUTHOR), Leavesley, Matthew (AUTHOR), Brucato, Nicolas (AUTHOR), Cox, Murray P. (AUTHOR), Ricaut, François‐X (AUTHOR), Romero, Irene Gallego (AUTHOR), Eichler, Evan E. (AUTHOR)
Source: Science. 6/11/2026, Vol. 392 Issue 6803, p1-15. 15p.
Subjects: Genetic variation, Human genome, Pan-genome, Human evolution, Denisovans, Neanderthals, Biological evolution
Geographic Terms: New Guinea (Island), Papua New Guinea
Abstract: Genetic introgression from Neanderthals and Denisovans shaped modern human genomes; however, introgressed structural variants (SVs ≥ 50 base pairs) remain challenging to discover. We integrated high-quality phased assemblies from four new Papua New Guinea (PNG) haploid genomes with 94 published assemblies of diverse ancestry to infer an introgressed SV map. Introgressed SVs are enriched in genes (47%), including critical genomic disorder regions, and are most abundant in PNG genomes. We identified 11 centromeres likely derived from archaic hominins, adding unexplored diversity to centromere genomics. Pangenome genotyping of these 98 assemblies across 1363 samples revealed 16 adaptive SVs, many associated with immune-related genes and expression, in the PNG genomes. We hypothesize that archaic SVs contributed to reproductive success, underscoring introgression as a major force in human adaptive evolution. Editor's summary: Between 2 and 5% of modern Eurasian genomes are derived from admixture with Neanderthals and Denisovans, with Papua New Guineans bearing the largest fractions. However, Oceanian populations remain underrepresented in genetic studies, resulting in questions about the landscape of archaic introgression, including difficult-to-identify features such as structural variants. Hsieh et al. used long-read sequencing to identify archaic-derived structural variants in two Papua New Guinean individuals, finding many unique insertions and deletions, as well as 11 centromeres potentially inherited from archaic hominins. Reilly et al. examined whole-genome sequences from 177 Near Oceanian individuals, revealing many potentially adaptively introgressed regions. The authors tested some of these for their gene-regulatory potential using massively parallel reporter assays. Together, these studies give us greater insight into how archaic introgression has shaped these historically underrepresented populations. —Corinne Simonti INTRODUCTION: Interbreeding between archaic hominins, such as Neanderthals and Denisovans, and the ancestors of modern humans resulted in present-day Eurasian genomes carrying approximately 1 to 4% ancestry derived from these archaic groups, with the highest proportions observed in Papuans. Although most studies of archaic introgression have focused on single-nucleotide variants, structural variants (SVs)—insertions, deletions, and inversions—represent a major source of genetic diversity, with larger effects on gene regulation, phenotypes, and disease. However, the short and fragmented nature of ancient DNA and the limitations of short-read sequencing has prevented comprehensive detection of SVs, especially within complex regions, such as segmental duplications and centromeres. RATIONALE: Recent long-read sequencing and pangenome efforts allow complete resolution of SVs and repetitive regions in diverse human genomes. Leveraging high-quality haplotype-resolved assemblies from two newly sequenced Papuan genomes and 47 samples from the Human Pangenome Reference Consortium Release 1 (HPRCr1), we systematically mapped genome-wide introgressed SVs. These Papuan genomes fill a notable gap by capturing missing diversity in existing pangenome efforts. By integrating population genetic analyses, simulations, and pangenome graph–based genotyping in large cohorts, we identified archaic centromeres and adaptive SV introgression events, providing new insights into how structural variation has shaped human evolution and genetic diversity. RESULTS: The Papuan genome assemblies revealed numerous distinct SVs compared with the HPRCr1 assemblies, including several at biomedically relevant loci, such as the chromosome 15q13.3 region associated with idiopathic epilepsy and the 22q11.2 locus linked to DiGeorge syndrome, underscoring the importance of including underrepresented populations in genomic studies. Using these long-read assemblies, we constructed a comprehensive global introgression map encompassing 365.7 mega–base pairs (Mbp) of the human genome, revealing haplotype-resolved introgressed SVs spanning 0.6 to 2.4 Mbp per individual. The Papuan individuals carried the highest number of introgressed SVs (mean: 1909 alleles), whereas admixed Americans showed the lowest (mean: 769 alleles). Overall, 47% of introgressed SVs overlapped genes, highlighting their potential functional relevance. We applied pangenome-based genotyping and uncovered 16 adaptive SVs, which likely originated from archaic hominins. Our population genetic analyses indicated that these SVs rose rapidly in frequency among Papuans within the past 6000 years, potentially driven by post-Neolithic selective pressures associated with pathogen transmissions among regional populations. Lastly, we introduce a strategy to provide evidence of 11 introgressed archaic centromeres, representing megabase-scale archaic haplotypes spanning up to 5.1 Mbp, among the longest introgressed segments identified in modern humans. CONCLUSION: The assemblies and results reported in this study provide a powerful resource and framework for investigating the evolutionary history and selection of SVs across modern and ancient genomes. This approach highlights the power of integrating nearly complete modern human genomes from a pangenome with archaic DNA, providing distinctive glimpses into the ancient SV genome architecture and their potential functional significance. Global map of introgressed SVs and selection.: Genome-wide introgressed sequences and SVs, such as deletions (red) and insertions (orange), derived from Neanderthal (green) and Denisovan (blue) genomes were identified using haplotype-phased assemblies from 47 HPRCr1 (black) and 2 Papuan (dark cyan) samples. Introgressed SVs were further classified based on whether they overlap with genes or centromeres. Haplotypes showing selection signals (blue segment) in linked single-nucleotide polymorphisms and SVs (gray and orange circles above the dotted line, respectively), such as insertions (dashed lines in the double helix), were identified as candidates for adaptive SV introgression. [ABSTRACT FROM AUTHOR]
Copyright of Science is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
Full text is not displayed to guests.
FullText Links:
  – Type: pdflink
Text:
  Availability: 1
Header DbId: pbh
DbLabel: Psychology and Behavioral Sciences Collection
An: 194526212
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: A global map for introgressed structural variation and selection in humans.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Hsieh%2C+PingHsun%22">Hsieh, PingHsun</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Soisangwan%2C+Natthapon%22">Soisangwan, Natthapon</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gordon%2C+David+S%2E%22">Gordon, David S.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Javidh%2C+Athef%22">Javidh, Athef</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Harvey%2C+William+T%2E%22">Harvey, William T.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Porubsky%2C+David%22">Porubsky, David</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hoekzema%2C+Kendra%22">Hoekzema, Kendra</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Baker%2C+Carl%22">Baker, Carl</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Munson%2C+Katherine+M%2E%22">Munson, Katherine M.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kinipi%2C+Christopher%22">Kinipi, Christopher</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Leavesley%2C+Matthew%22">Leavesley, Matthew</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Brucato%2C+Nicolas%22">Brucato, Nicolas</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cox%2C+Murray+P%2E%22">Cox, Murray P.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ricaut%2C+François‐X%22">Ricaut, François‐X</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Romero%2C+Irene+Gallego%22">Romero, Irene Gallego</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Eichler%2C+Evan+E%2E%22">Eichler, Evan E.</searchLink> (AUTHOR)
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%22Science%22">Science</searchLink>. 6/11/2026, Vol. 392 Issue 6803, p1-15. 15p.
– Name: Subject
  Label: Subjects
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Genetic+variation%22">Genetic variation</searchLink><br /><searchLink fieldCode="DE" term="%22Human+genome%22">Human genome</searchLink><br /><searchLink fieldCode="DE" term="%22Pan-genome%22">Pan-genome</searchLink><br /><searchLink fieldCode="DE" term="%22Human+evolution%22">Human evolution</searchLink><br /><searchLink fieldCode="DE" term="%22Denisovans%22">Denisovans</searchLink><br /><searchLink fieldCode="DE" term="%22Neanderthals%22">Neanderthals</searchLink><br /><searchLink fieldCode="DE" term="%22Biological+evolution%22">Biological evolution</searchLink>
– Name: SubjectGeographic
  Label: Geographic Terms
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22New+Guinea+%28Island%29%22">New Guinea (Island)</searchLink><br /><searchLink fieldCode="DE" term="%22Papua+New+Guinea%22">Papua New Guinea</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Genetic introgression from Neanderthals and Denisovans shaped modern human genomes; however, introgressed structural variants (SVs ≥ 50 base pairs) remain challenging to discover. We integrated high-quality phased assemblies from four new Papua New Guinea (PNG) haploid genomes with 94 published assemblies of diverse ancestry to infer an introgressed SV map. Introgressed SVs are enriched in genes (47%), including critical genomic disorder regions, and are most abundant in PNG genomes. We identified 11 centromeres likely derived from archaic hominins, adding unexplored diversity to centromere genomics. Pangenome genotyping of these 98 assemblies across 1363 samples revealed 16 adaptive SVs, many associated with immune-related genes and expression, in the PNG genomes. We hypothesize that archaic SVs contributed to reproductive success, underscoring introgression as a major force in human adaptive evolution. Editor's summary: Between 2 and 5% of modern Eurasian genomes are derived from admixture with Neanderthals and Denisovans, with Papua New Guineans bearing the largest fractions. However, Oceanian populations remain underrepresented in genetic studies, resulting in questions about the landscape of archaic introgression, including difficult-to-identify features such as structural variants. Hsieh et al. used long-read sequencing to identify archaic-derived structural variants in two Papua New Guinean individuals, finding many unique insertions and deletions, as well as 11 centromeres potentially inherited from archaic hominins. Reilly et al. examined whole-genome sequences from 177 Near Oceanian individuals, revealing many potentially adaptively introgressed regions. The authors tested some of these for their gene-regulatory potential using massively parallel reporter assays. Together, these studies give us greater insight into how archaic introgression has shaped these historically underrepresented populations. —Corinne Simonti INTRODUCTION: Interbreeding between archaic hominins, such as Neanderthals and Denisovans, and the ancestors of modern humans resulted in present-day Eurasian genomes carrying approximately 1 to 4% ancestry derived from these archaic groups, with the highest proportions observed in Papuans. Although most studies of archaic introgression have focused on single-nucleotide variants, structural variants (SVs)—insertions, deletions, and inversions—represent a major source of genetic diversity, with larger effects on gene regulation, phenotypes, and disease. However, the short and fragmented nature of ancient DNA and the limitations of short-read sequencing has prevented comprehensive detection of SVs, especially within complex regions, such as segmental duplications and centromeres. RATIONALE: Recent long-read sequencing and pangenome efforts allow complete resolution of SVs and repetitive regions in diverse human genomes. Leveraging high-quality haplotype-resolved assemblies from two newly sequenced Papuan genomes and 47 samples from the Human Pangenome Reference Consortium Release 1 (HPRCr1), we systematically mapped genome-wide introgressed SVs. These Papuan genomes fill a notable gap by capturing missing diversity in existing pangenome efforts. By integrating population genetic analyses, simulations, and pangenome graph–based genotyping in large cohorts, we identified archaic centromeres and adaptive SV introgression events, providing new insights into how structural variation has shaped human evolution and genetic diversity. RESULTS: The Papuan genome assemblies revealed numerous distinct SVs compared with the HPRCr1 assemblies, including several at biomedically relevant loci, such as the chromosome 15q13.3 region associated with idiopathic epilepsy and the 22q11.2 locus linked to DiGeorge syndrome, underscoring the importance of including underrepresented populations in genomic studies. Using these long-read assemblies, we constructed a comprehensive global introgression map encompassing 365.7 mega–base pairs (Mbp) of the human genome, revealing haplotype-resolved introgressed SVs spanning 0.6 to 2.4 Mbp per individual. The Papuan individuals carried the highest number of introgressed SVs (mean: 1909 alleles), whereas admixed Americans showed the lowest (mean: 769 alleles). Overall, 47% of introgressed SVs overlapped genes, highlighting their potential functional relevance. We applied pangenome-based genotyping and uncovered 16 adaptive SVs, which likely originated from archaic hominins. Our population genetic analyses indicated that these SVs rose rapidly in frequency among Papuans within the past 6000 years, potentially driven by post-Neolithic selective pressures associated with pathogen transmissions among regional populations. Lastly, we introduce a strategy to provide evidence of 11 introgressed archaic centromeres, representing megabase-scale archaic haplotypes spanning up to 5.1 Mbp, among the longest introgressed segments identified in modern humans. CONCLUSION: The assemblies and results reported in this study provide a powerful resource and framework for investigating the evolutionary history and selection of SVs across modern and ancient genomes. This approach highlights the power of integrating nearly complete modern human genomes from a pangenome with archaic DNA, providing distinctive glimpses into the ancient SV genome architecture and their potential functional significance. Global map of introgressed SVs and selection.: Genome-wide introgressed sequences and SVs, such as deletions (red) and insertions (orange), derived from Neanderthal (green) and Denisovan (blue) genomes were identified using haplotype-phased assemblies from 47 HPRCr1 (black) and 2 Papuan (dark cyan) samples. Introgressed SVs were further classified based on whether they overlap with genes or centromeres. Haplotypes showing selection signals (blue segment) in linked single-nucleotide polymorphisms and SVs (gray and orange circles above the dotted line, respectively), such as insertions (dashed lines in the double helix), were identified as candidates for adaptive SV introgression. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Science is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=194526212
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1126/science.adz7518
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 15
        StartPage: 1
    Subjects:
      – SubjectFull: Genetic variation
        Type: general
      – SubjectFull: Human genome
        Type: general
      – SubjectFull: Pan-genome
        Type: general
      – SubjectFull: Human evolution
        Type: general
      – SubjectFull: Denisovans
        Type: general
      – SubjectFull: Neanderthals
        Type: general
      – SubjectFull: Biological evolution
        Type: general
      – SubjectFull: New Guinea (Island)
        Type: general
      – SubjectFull: Papua New Guinea
        Type: general
    Titles:
      – TitleFull: A global map for introgressed structural variation and selection in humans.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Hsieh, PingHsun
      – PersonEntity:
          Name:
            NameFull: Soisangwan, Natthapon
      – PersonEntity:
          Name:
            NameFull: Gordon, David S.
      – PersonEntity:
          Name:
            NameFull: Javidh, Athef
      – PersonEntity:
          Name:
            NameFull: Harvey, William T.
      – PersonEntity:
          Name:
            NameFull: Porubsky, David
      – PersonEntity:
          Name:
            NameFull: Hoekzema, Kendra
      – PersonEntity:
          Name:
            NameFull: Baker, Carl
      – PersonEntity:
          Name:
            NameFull: Munson, Katherine M.
      – PersonEntity:
          Name:
            NameFull: Kinipi, Christopher
      – PersonEntity:
          Name:
            NameFull: Leavesley, Matthew
      – PersonEntity:
          Name:
            NameFull: Brucato, Nicolas
      – PersonEntity:
          Name:
            NameFull: Cox, Murray P.
      – PersonEntity:
          Name:
            NameFull: Ricaut, François‐X
      – PersonEntity:
          Name:
            NameFull: Romero, Irene Gallego
      – PersonEntity:
          Name:
            NameFull: Eichler, Evan E.
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 11
              M: 06
              Text: 6/11/2026
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-print
              Value: 00368075
          Numbering:
            – Type: volume
              Value: 392
            – Type: issue
              Value: 6803
          Titles:
            – TitleFull: Science
              Type: main
ResultId 1