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Duplication and retention biases of essential and non-essential genes revealed by systematic knockdown analyses.

Woods S, Coghlan A, Rivers D, Warnecke T, Jeffries SJ, Kwon T, Rogers A, Hurst LD, Ahringer J - PLoS Genet. (2013)

Bottom Line: When a duplicate gene has no apparent loss-of-function phenotype, it is commonly considered that the phenotype has been masked as a result of functional redundancy with the remaining paralog.We further find that duplicate pairs derived from essential and non-essential genes have contrasting evolutionary dynamics: whereas non-essential genes are both more often successfully duplicated (fixed) and lost, essential genes are less often duplicated but upon successful duplication are maintained over longer periods.We expect the fundamental evolutionary duplication dynamics presented here to be broadly applicable.

View Article: PubMed Central - PubMed

Affiliation: The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge, United Kingdom.

ABSTRACT
When a duplicate gene has no apparent loss-of-function phenotype, it is commonly considered that the phenotype has been masked as a result of functional redundancy with the remaining paralog. This is supported by indirect evidence showing that multi-copy genes show loss-of-function phenotypes less often than single-copy genes and by direct tests of phenotype masking using select gene sets. Here we take a systematic genome-wide RNA interference approach to assess phenotype masking in paralog pairs in the Caenorhabditis elegans genome. Remarkably, in contrast to expectations, we find that phenotype masking makes only a minor contribution to the low knockdown phenotype rate for duplicate genes. Instead, we find that non-essential genes are highly over-represented among duplicates, leading to a low observed loss-of-function phenotype rate. We further find that duplicate pairs derived from essential and non-essential genes have contrasting evolutionary dynamics: whereas non-essential genes are both more often successfully duplicated (fixed) and lost, essential genes are less often duplicated but upon successful duplication are maintained over longer periods. We expect the fundamental evolutionary duplication dynamics presented here to be broadly applicable.

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Phenotype masking and double knockdown phenotype rates grouped by phylogenetic age.(A) Masking rates (i.e. where the phenotype of the double knockdown was more severe than expected under a multiplicative model of interaction; this includes full and partial masking) for the subset of the 790 duplicate pairs (without a close third paralog) for which phylogenetic age could be estimated (n = 711 pairs for whole set; C. elegans n = 178; Caenorhabditis n = 442; Bilateria n = 57; Eukaryota n = 34). (B) Double knockdown phenotype rate for duplicate pairs in (A). (C) Masking rates for duplicate pairs in (A) considering only duplicates with a double knockdown phenotype (n = 155 pairs for whole set; C. elegans n = 8; Caenorhabditis n = 92; Bilateria n = 26; Eukaryota n = 29). Masking rates differ according to phylogenetic age (Fisher's test: P = 0.002), with a prevalence of masking amongst younger duplicate pairs. (D) Number of pairs analysed for duplicate pairs in (A).
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pgen-1003330-g002: Phenotype masking and double knockdown phenotype rates grouped by phylogenetic age.(A) Masking rates (i.e. where the phenotype of the double knockdown was more severe than expected under a multiplicative model of interaction; this includes full and partial masking) for the subset of the 790 duplicate pairs (without a close third paralog) for which phylogenetic age could be estimated (n = 711 pairs for whole set; C. elegans n = 178; Caenorhabditis n = 442; Bilateria n = 57; Eukaryota n = 34). (B) Double knockdown phenotype rate for duplicate pairs in (A). (C) Masking rates for duplicate pairs in (A) considering only duplicates with a double knockdown phenotype (n = 155 pairs for whole set; C. elegans n = 8; Caenorhabditis n = 92; Bilateria n = 26; Eukaryota n = 29). Masking rates differ according to phylogenetic age (Fisher's test: P = 0.002), with a prevalence of masking amongst younger duplicate pairs. (D) Number of pairs analysed for duplicate pairs in (A).

Mentions: Since a pair of duplicates will diverge over time, we would predict a lower rate of masking amongst older duplicate pairs than for younger pairs. However, surprisingly we find that overall (full or partial) and full masking rates are much higher for the 533 older pairs than the 178 younger pairs (4.9-fold and 3.4-fold, respectively Figure 2A and Figure S2).


Duplication and retention biases of essential and non-essential genes revealed by systematic knockdown analyses.

Woods S, Coghlan A, Rivers D, Warnecke T, Jeffries SJ, Kwon T, Rogers A, Hurst LD, Ahringer J - PLoS Genet. (2013)

Phenotype masking and double knockdown phenotype rates grouped by phylogenetic age.(A) Masking rates (i.e. where the phenotype of the double knockdown was more severe than expected under a multiplicative model of interaction; this includes full and partial masking) for the subset of the 790 duplicate pairs (without a close third paralog) for which phylogenetic age could be estimated (n = 711 pairs for whole set; C. elegans n = 178; Caenorhabditis n = 442; Bilateria n = 57; Eukaryota n = 34). (B) Double knockdown phenotype rate for duplicate pairs in (A). (C) Masking rates for duplicate pairs in (A) considering only duplicates with a double knockdown phenotype (n = 155 pairs for whole set; C. elegans n = 8; Caenorhabditis n = 92; Bilateria n = 26; Eukaryota n = 29). Masking rates differ according to phylogenetic age (Fisher's test: P = 0.002), with a prevalence of masking amongst younger duplicate pairs. (D) Number of pairs analysed for duplicate pairs in (A).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3649981&req=5

pgen-1003330-g002: Phenotype masking and double knockdown phenotype rates grouped by phylogenetic age.(A) Masking rates (i.e. where the phenotype of the double knockdown was more severe than expected under a multiplicative model of interaction; this includes full and partial masking) for the subset of the 790 duplicate pairs (without a close third paralog) for which phylogenetic age could be estimated (n = 711 pairs for whole set; C. elegans n = 178; Caenorhabditis n = 442; Bilateria n = 57; Eukaryota n = 34). (B) Double knockdown phenotype rate for duplicate pairs in (A). (C) Masking rates for duplicate pairs in (A) considering only duplicates with a double knockdown phenotype (n = 155 pairs for whole set; C. elegans n = 8; Caenorhabditis n = 92; Bilateria n = 26; Eukaryota n = 29). Masking rates differ according to phylogenetic age (Fisher's test: P = 0.002), with a prevalence of masking amongst younger duplicate pairs. (D) Number of pairs analysed for duplicate pairs in (A).
Mentions: Since a pair of duplicates will diverge over time, we would predict a lower rate of masking amongst older duplicate pairs than for younger pairs. However, surprisingly we find that overall (full or partial) and full masking rates are much higher for the 533 older pairs than the 178 younger pairs (4.9-fold and 3.4-fold, respectively Figure 2A and Figure S2).

Bottom Line: When a duplicate gene has no apparent loss-of-function phenotype, it is commonly considered that the phenotype has been masked as a result of functional redundancy with the remaining paralog.We further find that duplicate pairs derived from essential and non-essential genes have contrasting evolutionary dynamics: whereas non-essential genes are both more often successfully duplicated (fixed) and lost, essential genes are less often duplicated but upon successful duplication are maintained over longer periods.We expect the fundamental evolutionary duplication dynamics presented here to be broadly applicable.

View Article: PubMed Central - PubMed

Affiliation: The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge, United Kingdom.

ABSTRACT
When a duplicate gene has no apparent loss-of-function phenotype, it is commonly considered that the phenotype has been masked as a result of functional redundancy with the remaining paralog. This is supported by indirect evidence showing that multi-copy genes show loss-of-function phenotypes less often than single-copy genes and by direct tests of phenotype masking using select gene sets. Here we take a systematic genome-wide RNA interference approach to assess phenotype masking in paralog pairs in the Caenorhabditis elegans genome. Remarkably, in contrast to expectations, we find that phenotype masking makes only a minor contribution to the low knockdown phenotype rate for duplicate genes. Instead, we find that non-essential genes are highly over-represented among duplicates, leading to a low observed loss-of-function phenotype rate. We further find that duplicate pairs derived from essential and non-essential genes have contrasting evolutionary dynamics: whereas non-essential genes are both more often successfully duplicated (fixed) and lost, essential genes are less often duplicated but upon successful duplication are maintained over longer periods. We expect the fundamental evolutionary duplication dynamics presented here to be broadly applicable.

Show MeSH
Related in: MedlinePlus