The Role of Phylogenetically Conserved Elements in Shaping Patterns of Human Genomic Diversity.
Mol Biol Evol
; 35(9): 2284-2295, 2018 09 01.
Article
in En
| MEDLINE
| ID: mdl-30113695
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 (â¼100 bp), widely distributed (comprising â¼5% 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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Selection, Genetic
/
Genome, Human
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Conserved Sequence
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Genetic Linkage
/
Models, Genetic
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Mol Biol Evol
Journal subject:
BIOLOGIA MOLECULAR
Year:
2018
Type:
Article
Affiliation country:
Azerbaijan