Lineage-Specific Gene Duplication and Loss in Human and Great Ape Evolution

Fortna, Andrew; Kim, Young; MacLaren, Erik J.; Marshall, Kriste E.; Hahn, Gretchen; Meltesen, Lynne; Brenton, Matthew; Hink, Raquel; Burgers, Sonya; Hernandez‐Boussard, Tina; Karimpour-Fard, Anis; Glueck, Deborah H.; McGavran, Loris; Berry, Rebecca; Pollack, Jonathan R.; Sikela, James M.

doi:10.1371/journal.pbio.0020207

Cited by 269 publications

(317 citation statements)

References 48 publications

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“…Therefore, the average human has ∼3 times more AMY1 copies than chimpanzees, and bonobos may not have salivary amylase at all. Outgroup comparisons with other great apes suggest that AMY1 copy number was most likely gained in the human lineage, rather than lost in chimpanzees 21,22 . Given that AMY1 copy number is positively correlated with salivary amylase protein level in humans, it stands to reason that the human-specific increase in copy number may explain, at least in part, why salivary amylase protein levels are ∼6-8 times higher in humans than in chimpanzees 23 .…”

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confidence: 96%

Diet and the evolution of human amylase gene copy number variation

et al. 2007

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Starch consumption is a prominent characteristic of agricultural societies and hunter-gatherers in arid environments. In contrast, rainforest and circum-arctic hunter-gatherers and some pastoralists consume much less starch 1-3 . This behavioral variation raises the possibility that different selective pressures have acted on amylase, the enzyme responsible for starch hydrolysis 4 . We found that salivary amylase gene (AMY1) copy number is correlated positively with salivary amylase protein levels, and that individuals from populations with high-starch diets have on average more AMY1 copies than those with traditionally low-starch diets. Comparisons with other loci in a subset of these populations suggest that the level of AMY1 copy number differentiation is unusual. This example of positive selection on a copy number variable gene is one of the first in the human genome. Higher AMY1 copy numbers and protein levels likely improve the digestion of starchy foods, and may buffer against the fitness-reducing effects of intestinal disease. Hominin evolution is characterized by significant dietary shifts, facilitated in part by the development of stone tool technology, the control of fire, and most recently the domestication of plants and animals 5-7 . Starch, for instance, has become an increasingly prominent component of the human diet, particularly among agricultural societies 8 . It stands to reason, therefore, that studies of the evolution of amylase in humans and our close primate relatives may provide insight into our ecological history. Because the human salivary amylase gene (AMY1) shows extensive variation in copy number 9,10 , we first assess whether a functional relationship exists between AMY1 copy number and the level of amylase protein expression in

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confidence: 96%

Diet and the evolution of human amylase gene copy number variation

et al. 2007

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“…While there is some evidence that fixed deletions and duplications contribute to morphological differences between humans and great apes (McLean et al 2011;Charrier et al 2012;Dennis et al 2012), a comprehensive assessment of these differences at the level of the genome has not yet been performed. Previous studies of CNV have been predominated by array comparative genomic hybridization (CGH) experiments (Fortna et al 2004;Perry et al 2006;Dumas et al 2007;Gazave et al 2011;Locke et al 2011), which provide limited size resolution, are imprecise in absolute copy number differences, and are biased by probes derived from the human reference genome. Comparisons of reference genomes have been complicated by assessments of a single individual and distinguishing CNVs from assembly errors (The Chimpanzee Sequencing and Analysis Consortium 2005; Locke et al 2011;Ventura et al 2011;Prüfer et al 2012).…”

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confidence: 99%

Evolution and diversity of copy number variation in the great ape lineage

et al. 2013

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Copy number variation (CNV) contributes to disease and has restructured the genomes of great apes. The diversity and rate of this process, however, have not been extensively explored among great ape lineages. We analyzed 97 deeply sequenced great ape and human genomes and estimate 16% (469 Mb) of the hominid genome has been affected by recent CNV. We identify a comprehensive set of fixed gene deletions (n = 340) and duplications (n = 405) as well as >13.5 Mb of sequence that has been specifically lost on the human lineage. We compared the diversity and rates of copy number and single nucleotide variation across the hominid phylogeny. We find that CNV diversity partially correlates with single nucleotide diversity (r 2 = 0.5) and recapitulates the phylogeny of apes with few exceptions. Duplications significantly outpace deletions (2.8-fold). The load of segregating duplications remains significantly higher in bonobos, Western chimpanzees, and Sumatran orangutans-populations that have experienced recent genetic bottlenecks (P = 0.0014, 0.02, and 0.0088, respectively). The rate of fixed deletion has been more clocklike with the exception of the chimpanzee lineage, where we observe a twofold increase in the chimpanzee-bonobo ancestor (P = 4.79 3 10 -9 ) and increased deletion load among Western chimpanzees (P = 0.002). The latter includes the first genomic disorder in a chimpanzee with features resembling Smith-Magenis syndrome mediated by a chimpanzee-specific increase in segmental duplication complexity. We hypothesize that demographic effects, such as bottlenecks, have contributed to larger and more gene-rich segments being deleted in the chimpanzee lineage and that this effect, more generally, may account for episodic bursts in CNV during hominid evolution.

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“…For example, loci harboring human pathogenic CNVs that present high-frequency structural polymorphism in all great apes may have had special evolutionary relevance in adaptation and health. Previous studies of interspecific comparisons (e.g., Fortna et al 2004;Newman et al 2005;Perry et al 2006;Wilson et al 2006;Dumas et al 2007;Armengol et al 2010) provide no comparative information about speciesspecific polymorphism, for they only document human-specific losses and gains, while most intraspecific studies, such as that by Perry et al (2008) in chimpanzees, have so far focused on single species.…”

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Copy number variation analysis in the great apes reveals species-specific patterns of structural variation

Gazave¹,

Darré²,

Morcillo-Suárez³

et al. 2011

Genome Res.

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Copy number variants (CNVs) are increasingly acknowledged as an important source of evolutionary novelties in the human lineage. However, our understanding of their significance is still hindered by the lack of primate CNV data. We performed intraspecific comparative genomic hybridizations to identify loci harboring copy number variants in each of the four great apes: bonobos, chimpanzees, gorillas, and orangutans. For the first time, we could analyze differences in CNV location and frequency in these four species, and compare them with human CNVs and primate segmental duplication (SD) maps. In addition, for bonobo and gorilla, patterns of CNV and nucleotide diversity were studied in the same individuals. We show that CNVs have been subject to different selective pressures in different lineages. Evidence for purifying selection is stronger in gorilla CNVs overlapping genes, while positive selection appears to have driven the fixation of structural variants in the orangutan lineage. In contrast, chimpanzees and bonobos present high levels of common structural polymorphism, which is indicative of relaxed purifying selection together with the higher mutation rates induced by the known burst of segmental duplication in the ancestor of the African apes. Indeed, the impact of the duplication burst is noticeable by the fact that bonobo and chimpanzee share more CNVs with gorilla than expected. Finally, we identified a number of interesting genomic regions that present high-frequency CNVs in all great apes, while containing only very rare or even pathogenic structural variants in humans.

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Lineage-Specific Gene Duplication and Loss in Human and Great Ape Evolution

Cited by 269 publications

References 48 publications

Diet and the evolution of human amylase gene copy number variation

Diet and the evolution of human amylase gene copy number variation

Evolution and diversity of copy number variation in the great ape lineage

Copy number variation analysis in the great apes reveals species-specific patterns of structural variation

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