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Gene-dense autosomal chromosomes show evidence for increased selection

Gene-dense autosomal chromosomes show evidence for increased selection
Gene-dense autosomal chromosomes show evidence for increased selection
Purifying selection tends to reduce nucleotide and haplotype diversity leading to increased linkage disequilibrium. However, detection of evidence for selection is difficult as the signature is confounded by wide variation in the recombination rate which has a complex relationship with selection. The effective bottleneck time (the ratio of the linkage disequilibrium map to the genetic map in Morgans) controls for variability in recombination rate. Reduced effective bottleneck times indicate stronger residual linkage disequilibrium, consistent with increased selection. Using whole genome sequence data from one European and three Sub-Saharan African human populations we find, in the African samples, strong correlations between high gene densities and reduced effective bottleneck time for autosomal chromosomes. Although previous studies have shown unusually strong linkage disequilibrium for the sex chromosomes variation within the autosomes has not been recognised. The strongest relationship is between effective bottleneck time and the density of essential genes, which are likely targets of greater selective pressure (p = 0.006, for the 22 autosomes). The magnitude of the reduction in chromosome-specific effective bottleneck times from the least to the most gene-dense autosomes is ~17-21% for Sub-Saharan African populations. The effect size is greater in Sub-Saharan African populations, compared to a European sample, consistent with increased efficiency of selection in populations with larger effective population sizes which have not been subject to intense population bottlenecks as experienced by populations of European ancestry. The findings highlight the value of deeper analyses of selection within Sub-Saharan African populations.
0018-067X
774-783
Jabalameli, M.R.
d533e702-7a6b-4f2d-8947-352ea1dd769b
Horscroft, Clare
6ed6a58f-5fe9-4be0-a92e-bee5ea43aa8c
Vergara Lope Gracia, Norma, Alejandra
84ea3389-86d8-4b89-ad65-729173419305
Pengelly, Reuben
af97c0c1-b568-415c-9f59-1823b65be76d
Collins, Andrew
7daa83eb-0b21-43b2-af1a-e38fb36e2a64
Jabalameli, M.R.
d533e702-7a6b-4f2d-8947-352ea1dd769b
Horscroft, Clare
6ed6a58f-5fe9-4be0-a92e-bee5ea43aa8c
Vergara Lope Gracia, Norma, Alejandra
84ea3389-86d8-4b89-ad65-729173419305
Pengelly, Reuben
af97c0c1-b568-415c-9f59-1823b65be76d
Collins, Andrew
7daa83eb-0b21-43b2-af1a-e38fb36e2a64

Jabalameli, M.R., Horscroft, Clare, Vergara Lope Gracia, Norma, Alejandra, Pengelly, Reuben and Collins, Andrew (2019) Gene-dense autosomal chromosomes show evidence for increased selection. Heredity, 123 (6), 774-783. (doi:10.1038/s41437-019-0272-5).

Record type: Article

Abstract

Purifying selection tends to reduce nucleotide and haplotype diversity leading to increased linkage disequilibrium. However, detection of evidence for selection is difficult as the signature is confounded by wide variation in the recombination rate which has a complex relationship with selection. The effective bottleneck time (the ratio of the linkage disequilibrium map to the genetic map in Morgans) controls for variability in recombination rate. Reduced effective bottleneck times indicate stronger residual linkage disequilibrium, consistent with increased selection. Using whole genome sequence data from one European and three Sub-Saharan African human populations we find, in the African samples, strong correlations between high gene densities and reduced effective bottleneck time for autosomal chromosomes. Although previous studies have shown unusually strong linkage disequilibrium for the sex chromosomes variation within the autosomes has not been recognised. The strongest relationship is between effective bottleneck time and the density of essential genes, which are likely targets of greater selective pressure (p = 0.006, for the 22 autosomes). The magnitude of the reduction in chromosome-specific effective bottleneck times from the least to the most gene-dense autosomes is ~17-21% for Sub-Saharan African populations. The effect size is greater in Sub-Saharan African populations, compared to a European sample, consistent with increased efficiency of selection in populations with larger effective population sizes which have not been subject to intense population bottlenecks as experienced by populations of European ancestry. The findings highlight the value of deeper analyses of selection within Sub-Saharan African populations.

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Accepted/In Press date: 16 September 2019
e-pub ahead of print date: 1 October 2019
Published date: 1 December 2019

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Local EPrints ID: 434732
URI: http://eprints.soton.ac.uk/id/eprint/434732
ISSN: 0018-067X
PURE UUID: 48d586a3-b20f-47b3-a27c-1ef89fffee7a
ORCID for M.R. Jabalameli: ORCID iD orcid.org/0000-0002-7762-0529
ORCID for Reuben Pengelly: ORCID iD orcid.org/0000-0001-7022-645X
ORCID for Andrew Collins: ORCID iD orcid.org/0000-0001-7108-0771

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Date deposited: 07 Oct 2019 16:30
Last modified: 17 Mar 2024 02:37

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Contributors

Author: M.R. Jabalameli ORCID iD
Author: Clare Horscroft
Author: Norma, Alejandra Vergara Lope Gracia
Author: Reuben Pengelly ORCID iD
Author: Andrew Collins ORCID iD

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