Gene dosage and gene duplicability.

Abstract:

:The evolutionary process leading to the fixation of newly duplicated genes is not well understood. It was recently proposed that the fixation of duplicate genes is frequently driven by positive selection for increased gene dosage (i.e., the gene dosage hypothesis), because haploinsufficient genes were reported to have more paralogs than haplosufficient genes in the human genome. However, the previous analysis incorrectly assumed that the presence of dominant abnormal alleles of a human gene means that the gene is haploinsufficient, ignoring the fact that many dominant abnormal alleles arise from gain-of-function mutations. Here we show in both humans and yeast that haploinsufficient genes generally do not duplicate more frequently than haplosufficient genes. Yeast haploinsufficient genes do exhibit enhanced retention after whole-genome duplication compared to haplosufficient genes if they encode members of stable protein complexes, but the same phenomenon is absent if the genes do not encode protein complex members, suggesting that the dosage balance effect rather than the dosage effect is the underlying cause of the phenomenon. On the basis of these and other results, we conclude that selection for higher gene dosage does not play a major role in driving the fixation of duplication genes.

journal_name

Genetics

journal_title

Genetics

authors

Qian W,Zhang J

doi

10.1534/genetics.108.090936

subject

Has Abstract

pub_date

2008-08-01 00:00:00

pages

2319-24

issue

4

eissn

0016-6731

issn

1943-2631

pii

genetics.108.090936

journal_volume

179

pub_type

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