Positive selection on gene expression in the human brain

Philipp Khaitovich; Kun Tang; Henriette Franz; Janet Kelso; Ines Hellmann; Wolfgang Enard; Michael Lachmann; Svante Pääbo

doi:10.1016/j.cub.2006.03.082

Positive selection on gene expression in the human brain

Philipp Khaitovich, Kun Tang, Henriette Franz, Janet Kelso, Ines Hellmann, Wolfgang Enard, Michael Lachmann, Svante Pääbo

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

48 Citationer (Scopus)

Abstract

Udgivelsesdato: 23 May 2006

Originalsprog	Engelsk
Tidsskrift	Current Biology
Vol/bind	16
Udgave nummer	10
Sider (fra-til)	R356-R358
ISSN	0960-9822
DOI	https://doi.org/10.1016/j.cub.2006.03.082
Status	Udgivet - 2006

Adgang til dokumentet

10.1016/j.cub.2006.03.082

Citationsformater

@article{1723de606c3711dcbee902004c4f4f50,

title = "Positive selection on gene expression in the human brain",

abstract = "Recent work has shown that the expression levels of genes transcribed in the brains of humans and chimpanzees have changed less than those of genes transcribed in other tissues [1]. However, when gene expression changes are mapped onto the evolutionary lineage in which they occurred, the brain shows more changes than other tissues in the human lineage compared to the chimpanzee lineage [1], [2] and [3]. There are two possible explanations for this: either positive selection drove more gene expression changes to fixation in the human brain than in the chimpanzee brain, or genes expressed in the brain experienced less purifying selection in humans than in chimpanzees, i.e. gene expression in the human brain is functionally less constrained. The first scenario would be supported if genes that changed their expression in the brain in the human lineage showed more selective sweeps than other genes. Unfortunately, current human genome-wide DNA sequence variation do not allow signatures of selective sweeps to be inferred using frequency-based approaches [4] and [5]. However, estimates of linkage disequilibrium (LD) - i.e. the extent of non-random association of alleles along chromosomes - are expected to be largely unaffected by frequency ascertainment bias [5], and selective sweeps are expected to increase the amount of LD around a selected gene variant [6], [7], [8] and 9 P.C. Sabeti, D.E. Reich, J.M. Higgins, H.Z. Levine, D.J. Richter and S.F. Schaffner et al., Detecting recent positive selection in the human genome from haplotype structure, Nature 419 (2002), pp. 832-837.",

author = "Philipp Khaitovich and Kun Tang and Henriette Franz and Janet Kelso and Ines Hellmann and Wolfgang Enard and Michael Lachmann and Svante P{\"a}{\"a}bo",

year = "2006",

doi = "10.1016/j.cub.2006.03.082",

language = "English",

volume = "16",

pages = "R356--R358",

journal = "Current Biology",

issn = "0960-9822",

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T1 - Positive selection on gene expression in the human brain

AU - Khaitovich, Philipp

AU - Tang, Kun

AU - Franz, Henriette

AU - Kelso, Janet

AU - Hellmann, Ines

AU - Enard, Wolfgang

AU - Lachmann, Michael

AU - Pääbo, Svante

PY - 2006

Y1 - 2006

N2 - Recent work has shown that the expression levels of genes transcribed in the brains of humans and chimpanzees have changed less than those of genes transcribed in other tissues [1]. However, when gene expression changes are mapped onto the evolutionary lineage in which they occurred, the brain shows more changes than other tissues in the human lineage compared to the chimpanzee lineage [1], [2] and [3]. There are two possible explanations for this: either positive selection drove more gene expression changes to fixation in the human brain than in the chimpanzee brain, or genes expressed in the brain experienced less purifying selection in humans than in chimpanzees, i.e. gene expression in the human brain is functionally less constrained. The first scenario would be supported if genes that changed their expression in the brain in the human lineage showed more selective sweeps than other genes. Unfortunately, current human genome-wide DNA sequence variation do not allow signatures of selective sweeps to be inferred using frequency-based approaches [4] and [5]. However, estimates of linkage disequilibrium (LD) - i.e. the extent of non-random association of alleles along chromosomes - are expected to be largely unaffected by frequency ascertainment bias [5], and selective sweeps are expected to increase the amount of LD around a selected gene variant [6], [7], [8] and 9 P.C. Sabeti, D.E. Reich, J.M. Higgins, H.Z. Levine, D.J. Richter and S.F. Schaffner et al., Detecting recent positive selection in the human genome from haplotype structure, Nature 419 (2002), pp. 832-837.

AB - Recent work has shown that the expression levels of genes transcribed in the brains of humans and chimpanzees have changed less than those of genes transcribed in other tissues [1]. However, when gene expression changes are mapped onto the evolutionary lineage in which they occurred, the brain shows more changes than other tissues in the human lineage compared to the chimpanzee lineage [1], [2] and [3]. There are two possible explanations for this: either positive selection drove more gene expression changes to fixation in the human brain than in the chimpanzee brain, or genes expressed in the brain experienced less purifying selection in humans than in chimpanzees, i.e. gene expression in the human brain is functionally less constrained. The first scenario would be supported if genes that changed their expression in the brain in the human lineage showed more selective sweeps than other genes. Unfortunately, current human genome-wide DNA sequence variation do not allow signatures of selective sweeps to be inferred using frequency-based approaches [4] and [5]. However, estimates of linkage disequilibrium (LD) - i.e. the extent of non-random association of alleles along chromosomes - are expected to be largely unaffected by frequency ascertainment bias [5], and selective sweeps are expected to increase the amount of LD around a selected gene variant [6], [7], [8] and 9 P.C. Sabeti, D.E. Reich, J.M. Higgins, H.Z. Levine, D.J. Richter and S.F. Schaffner et al., Detecting recent positive selection in the human genome from haplotype structure, Nature 419 (2002), pp. 832-837.

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DO - 10.1016/j.cub.2006.03.082

M3 - Journal article

C2 - 16618540

SN - 0960-9822

VL - 16

SP - R356-R358

JO - Current Biology

JF - Current Biology

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