The role of phylogenetically conserved elements in shaping patterns of human genomic diversity

August Eric Woerner, Krishna R. Veeramah, Joseph C. Watkins, Michael F. Hammer

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

Evolutionary genetic studies have shown a positive correlation between levels of nucleotide diversity and either rates of recombination or genetic distance to genes. Both positive-directional and purifying selection have been offered as the source of these correlations via genetic hitchhiking and background selection, respectively. Phylogenetically conserved elements (CEs) are short (100 bp), widely distributed (comprising5% of genome), sequences that are often found far from genes. While the function of many CEs is unknown, CEs also are associated with reduced diversity at linked sites. Using high coverage (>80) whole genome data from two human populations, the Yoruba and the CEU, we perform fine scale evaluations of diversity, rates of recombination, and linkage to genes. We find that the local rate of recombination has a stronger effect on levels of diversity than linkage to genes, and that these effects of recombination persist even in regions far from genes. Our whole genome modeling demonstrates that, rather than recombination or GC-biased gene conversion, selection on sites within or linked to CEs better explains the observed genomic diversity patterns. A major implication is that very few sites in the human genome are predicted to be free of the effects of selection. These sites, which we refer to as the human "neutralome," comprise only 1.2% of the autosomes and 5.1% of the X chromosome. Demographic analysis of the neutralome reveals larger population sizes and lower rates of growth for ancestral human populations than inferred by previous analyses.

Original languageEnglish
Pages (from-to)2284-2295
Number of pages12
JournalMolecular Biology and Evolution
Volume35
Issue number9
DOIs
StatePublished - 1 Jan 2018

Fingerprint

Genetic Recombination
genomics
recombination
gene
genome
Genes
Genome
genes
human population
linkage (genetics)
Gene Conversion
gene conversion
autosomes
X Chromosome
Human Genome
X chromosome
Population Density
genetic correlation
Population
genetic distance

Keywords

  • Background selection
  • Diversity
  • Genetic hitchhiking
  • Null model.
  • Phylogenetic conserved elements
  • Recombination

Cite this

Woerner, August Eric ; Veeramah, Krishna R. ; Watkins, Joseph C. ; Hammer, Michael F. / The role of phylogenetically conserved elements in shaping patterns of human genomic diversity. In: Molecular Biology and Evolution. 2018 ; Vol. 35, No. 9. pp. 2284-2295.
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The role of phylogenetically conserved elements in shaping patterns of human genomic diversity. / Woerner, August Eric; Veeramah, Krishna R.; Watkins, Joseph C.; Hammer, Michael F.

In: Molecular Biology and Evolution, Vol. 35, No. 9, 01.01.2018, p. 2284-2295.

Research output: Contribution to journalArticleResearchpeer-review

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N2 - Evolutionary genetic studies have shown a positive correlation between levels of nucleotide diversity and either rates of recombination or genetic distance to genes. Both positive-directional and purifying selection have been offered as the source of these correlations via genetic hitchhiking and background selection, respectively. Phylogenetically conserved elements (CEs) are short (100 bp), widely distributed (comprising5% of genome), sequences that are often found far from genes. While the function of many CEs is unknown, CEs also are associated with reduced diversity at linked sites. Using high coverage (>80) whole genome data from two human populations, the Yoruba and the CEU, we perform fine scale evaluations of diversity, rates of recombination, and linkage to genes. We find that the local rate of recombination has a stronger effect on levels of diversity than linkage to genes, and that these effects of recombination persist even in regions far from genes. Our whole genome modeling demonstrates that, rather than recombination or GC-biased gene conversion, selection on sites within or linked to CEs better explains the observed genomic diversity patterns. A major implication is that very few sites in the human genome are predicted to be free of the effects of selection. These sites, which we refer to as the human "neutralome," comprise only 1.2% of the autosomes and 5.1% of the X chromosome. Demographic analysis of the neutralome reveals larger population sizes and lower rates of growth for ancestral human populations than inferred by previous analyses.

AB - Evolutionary genetic studies have shown a positive correlation between levels of nucleotide diversity and either rates of recombination or genetic distance to genes. Both positive-directional and purifying selection have been offered as the source of these correlations via genetic hitchhiking and background selection, respectively. Phylogenetically conserved elements (CEs) are short (100 bp), widely distributed (comprising5% of genome), sequences that are often found far from genes. While the function of many CEs is unknown, CEs also are associated with reduced diversity at linked sites. Using high coverage (>80) whole genome data from two human populations, the Yoruba and the CEU, we perform fine scale evaluations of diversity, rates of recombination, and linkage to genes. We find that the local rate of recombination has a stronger effect on levels of diversity than linkage to genes, and that these effects of recombination persist even in regions far from genes. Our whole genome modeling demonstrates that, rather than recombination or GC-biased gene conversion, selection on sites within or linked to CEs better explains the observed genomic diversity patterns. A major implication is that very few sites in the human genome are predicted to be free of the effects of selection. These sites, which we refer to as the human "neutralome," comprise only 1.2% of the autosomes and 5.1% of the X chromosome. Demographic analysis of the neutralome reveals larger population sizes and lower rates of growth for ancestral human populations than inferred by previous analyses.

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