Fixation of the Human-Specific CMP-<i>N</i>-Acetylneuraminic Acid Hydroxylase Pseudogene and Implications of Haplotype Diversity for Human Evolution

Hayakawa, Toshiyuki; Aki, Ikuko; Varki, Ajit; Satta, Yoko; Takahata, Naoyuki

doi:10.1534/genetics.105.046995

Cited by 80 publications

(71 citation statements)

References 52 publications

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“…Except for one gene (Garrigan et al 2005b), the ancient TMRCA of these genes is attributed to the presence of two distinct lineages in Africa (Satta and Takahata 2004). In particular, Hayakawa et al (2006) show that the TMRCA at the CMP-N-acetylneuraminic acid hydroxylase (CMAH) locus is 2.9 MY and suggest that this rather ancient TMRCA may result from partially isolated populations in the Pleistocene period in Africa. To compare the TMRCA at ASAH1 with that at other loci, we applied the HKA test to the nucleotide diversity and divergence at 10 loci including CMAH (Hayakawa et al 2006) and those at ASAH1, but no significant differences are detected in the test.…”

Section: Resultsmentioning

confidence: 92%

“…This is relatively old compared to the average TMRCA of 0.8 MY, if N e ¼ 10 4 and g ¼ 20 years (Takahata 1993;Klein and Takahata 2002). However, there are several reports about genes with TMRCA .2 MY (Harris and Hey 1999;Barreiro et al 2005;Garrigan et al 2005a;Stefansson et al 2005;Garrigan and Hammer 2006;Hayakawa et al 2006). Except for one gene (Garrigan et al 2005b), the ancient TMRCA of these genes is attributed to the presence of two distinct lineages in Africa (Satta and Takahata 2004).…”

Section: Resultsmentioning

confidence: 99%

“…In particular, Hayakawa et al (2006) show that the TMRCA at the CMP-N-acetylneuraminic acid hydroxylase (CMAH) locus is 2.9 MY and suggest that this rather ancient TMRCA may result from partially isolated populations in the Pleistocene period in Africa. To compare the TMRCA at ASAH1 with that at other loci, we applied the HKA test to the nucleotide diversity and divergence at 10 loci including CMAH (Hayakawa et al 2006) and those at ASAH1, but no significant differences are detected in the test. This suggests that the TMRCA at ASAH1 is not exceptional (supplemental Table 7 at http://www.genetics.org/supplemental/).…”

Section: Resultsmentioning

confidence: 99%

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Population Genetic Analysis of the N-Acylsphingosine Amidohydrolase Gene Associated With Mental Activity in Humans

Kim

Satta

2008

Genetics

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To understand the evolution of human mental activity, we performed population genetic analyses of nucleotide sequences ($11 kb) from a worldwide sample of 60 chromosomes of the N-acylsphingosine amidohydrolase (ASAH1) gene. ASAH1 hydrolyzes ceramides and regulates neuronal development, and its deficiency often results in mental retardation. In the region ($4.4 kb) encompassing exons 3 and 4 of this gene, two distinct lineages (V and M) have been segregating in the human population for 2.4 6 0.4 million years (MY). The persistence of these two lineages is attributed to ancient population structure of humans in Africa. However, all haplotypes belonging to the V lineage exhibit strong linkage disequilibrium, a high frequency (62%), and small nucleotide diversity (p ¼ 0.05%). These features indicate a signature of positive Darwinian selection for the V lineage. Compared with the orthologs in mammals and birds, it is only Val at amino acid site 72 that is found exclusively in the V lineage in humans, suggesting that this Val is a likely target of positive selection. Computer simulation confirms that demographic models of modern humans except for the ancient population structure cannot explain the presence of two distinct lineages, and neutrality is incompatible with the observed small genetic variation of the V lineage at ASAH1. On the basis of the above observations, it is argued that positive selection is possibly operating on ASAH1 in the modern human population.

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Section: Resultsmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Population Genetic Analysis of the N-Acylsphingosine Amidohydrolase Gene Associated With Mental Activity in Humans

Kim

Satta

2008

Genetics

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“…1 A), which posit a single and recent African origin for all modern humans, are mainly supported by mitochondrial DNA (mtDNA) and Y-chromosome polymorphisms (4), by the current lack of Neanderthal mtDNA genes in modern humans (10), and by gradients of nuclear genetic diversity from Africa toward the Americas (4,11). Recent examination of nuclear DNA has, however, revealed some polymorphism patterns that were judged incompatible with a pure African replacement scenario (7,(12)(13)(14)(15)(16)(17). For instance, the presence of very old lineages in Africa and Asia raised claims for some degree of interbreeding between modern and archaic Homo forms (13,14,16,17).…”

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confidence: 99%

Statistical evaluation of alternative models of human evolution

Fagundes

Ray

Beaumont

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

545

520

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An appropriate model of recent human evolution is not only important to understand our own history, but it is necessary to disentangle the effects of demography and selection on genome diversity. Although most genetic data support the view that our species originated recently in Africa, it is still unclear if it completely replaced former members of the Homo genus, or if some interbreeding occurred during its range expansion. Several scenarios of modern human evolution have been proposed on the basis of molecular and paleontological data, but their likelihood has never been statistically assessed. Using DNA data from 50 nuclear loci sequenced in African, Asian and Native American samples, we show here by extensive simulations that a simple African replacement model with exponential growth has a higher probability (78%) as compared with alternative multiregional evolution or assimilation scenarios. A Bayesian analysis of the data under this best supported model points to an origin of our species Ϸ141 thousand years ago (Kya), an exit out-of-Africa Ϸ51 Kya, and a recent colonization of the Americas Ϸ10.5 Kya. We also find that the African replacement model explains not only the shallow ancestry of mtDNA or Y-chromosomes but also the occurrence of deep lineages at some autosomal loci, which has been formerly interpreted as a sign of interbreeding with Homo erectus.Bayesian analysis ͉ DNA nuclear data ͉ multiregional hypothesis ͉ out of Africa hypothesis

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“…This means that for RRM2P4, which has an ancient TMRCA, we cannot be confident about where archaic admixture may have occurred geographically. In this regard, it is interesting to note that a growing number of loci have been discovered with two deeply divergent lineages where both the major and the minor types are present only in African populations (Barreiro et al 2005;Garrigan et al 2005a;Hayakawa et al 2006). This supports models in which anatomically modern humans descend from a structured ancestral African population (Garrigan and Hammer 2006).…”

Section: à9mentioning

confidence: 63%

Testing for Archaic Hominin Admixture on the X Chromosome: Model Likelihoods for the Modern Human RRM2P4 Region From Summaries of Genealogical Topology Under the Structured Coalescent

Cox¹,

Mendez²,

Karafet³

et al. 2008

Genetics

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A 2.4-kb stretch within the RRM2P4 region of the X chromosome, previously sequenced in a sample of 41 globally distributed humans, displayed both an ancient time to the most recent common ancestor (e.g., a TMRCA of $2 million years) and a basal clade composed entirely of Asian sequences. This pattern was interpreted to reflect a history of introgressive hybridization from archaic hominins (most likely Asian Homo erectus) into the anatomically modern human genome. Here, we address this hypothesis by resequencing the 2.4-kb RRM2P4 region in 131 African and 122 non-African individuals and by extending the length of sequence in a window of 16.5 kb encompassing the RRM2P4 pseudogene in a subset of 90 individuals. We find that both the ancient TMRCA and the skew in non-African representation in one of the basal clades are essentially limited to the central 2.4-kb region. We define a new summary statistic called the minimum clade proportion (p mc ), which quantifies the proportion of individuals from a specified geographic region in each of the two basal clades of a binary gene tree, and then employ coalescent simulations to assess the likelihood of the observed central RRM2P4 genealogy under two alternative views of human evolutionary history: recent African replacement (RAR) and archaic admixture (AA). A molecular-clock-based TMRCA estimate of 2.33 million years is a statistical outlier under the RAR model; however, the large variance associated with this estimate makes it difficult to distinguish the predictions of the human origins models tested here. The p mc summary statistic, which has improved power with larger samples of chromosomes, yields values that are significantly unlikely under the RAR model and fit expectations better under a range of archaic admixture scenarios.

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Fixation of the Human-Specific CMP-N-Acetylneuraminic Acid Hydroxylase Pseudogene and Implications of Haplotype Diversity for Human Evolution

Cited by 80 publications

References 52 publications

Population Genetic Analysis of the N-Acylsphingosine Amidohydrolase Gene Associated With Mental Activity in Humans

Population Genetic Analysis of the N-Acylsphingosine Amidohydrolase Gene Associated With Mental Activity in Humans

Statistical evaluation of alternative models of human evolution

Testing for Archaic Hominin Admixture on the X Chromosome: Model Likelihoods for the Modern Human RRM2P4 Region From Summaries of Genealogical Topology Under the Structured Coalescent

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