Over the past four decades, molecular studies have yielded two primary models for understanding t... more Over the past four decades, molecular studies have yielded two primary models for understanding the uniparental DNA phylogenetic trees of modern humans: the Out of Africa (OOA) and the Out of East Asia (OOEA) models. These models differ in their underlying assumptions, particularly in relation to early stem haplotypes, even though they share many haplotype relationships. Leveraging the wealth of new genetic variants unveiled through the comprehensive sequencing of 43 diverse human Y chromosomes, we here investigated the presence of shared variants among different haplotypes to determine which model better aligns with the genetic data. We validated our approach by confirming numerous well-established haplotype relationships that are consistent with both the OOA and OOEA models. Remarkably, our analysis revealed a compelling pattern: we were able to corroborate the existence of stem haplotypes specific to the OOEA model, but not those exclusive to the OOA model. For instance, we found...
Human genetic diversity remains to be better understood. We here analyzed data from the 1000 Geno... more Human genetic diversity remains to be better understood. We here analyzed data from the 1000 Genomes Project and defined group specific fixed alleles (GSFAs) as those that are likely fixed in one ethnic group but non-fixed in at least one other group. The fraction of derived alleles in GSFAs indicates relative distance to apes because such alleles are absent in apes. Our results show that different groups differed in GSFA numbers consistent with known genetic diversity patterns, but also differed in the fraction of derived alleles in GSFAs throughout the entire genome, with East Asians having the largest fraction, followed by South Asians, Europeans, Native Americans, and Africans. Fast evolving sites such as intergenic regions were enriched with derived alleles and showed greater differences in GSFA numbers between East Asians and Africans. Furthermore, GSFAs in East Asians are mostly not fixed in other groups especially Africans, which was particularly more pronounced for fast evo...
The RIZ (G3B/MTB-Zf) gene was first isolated based on its ability to bind to the retinoblastoma p... more The RIZ (G3B/MTB-Zf) gene was first isolated based on its ability to bind to the retinoblastoma protein (Rb). An acidic, approximately 100-amino-acid region around the Rb-binding motif of RIZ has structural and antigenic similarity to the conserved sequences of the E1A viral oncogene. We show here that this region interacts specifically with the E1A-binding domain of Rb. This interaction could be disrupted by E1A or by a peptide of RIZ homologous to the CR2 motif of E1A which is involved in binding to Rb family proteins. Also like E1A, RIZ can form a ternary complex with Rb and E2F1. Despite this similarity to E1A, however, RIZ could not bind to the Rb family proteins p107 and p130 in vitro. The data show that the RIZ CR2 motif can mediate differential binding to Rb family proteins. We also mapped the shared antigenic determinant between RIZ and E1A to a conserved sequence, designated CE1, which is located in the C terminus of E1A. Unlike that of ETA, the CE1 motif of RIZ is located...
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research, 1990
The retinoblastoma (RB) gene encodes a nuclear phosphoprotein with a molecular weight of 110,000 ... more The retinoblastoma (RB) gene encodes a nuclear phosphoprotein with a molecular weight of 110,000 (pp110RB) associated with DNA-binding activity. This sequence-nonspecific DNA binding activity was further studied by Southwestern and DNA-cellulose chromatography using purified fusion proteins expressed in Escherichia coli. Three fusion proteins, containing amino acids 612-775, 776-928, and 612-928 of pp110RB, bound to DNA; the binding affinity of the latter was approximately 20-fold higher than those of either smaller region. Other regions of pp110RB had no detectable binding activity, indicating that the carboxyl-terminal region of the RB protein is the major domain responsible for interacting with DNA. Since several potential phosphorylation sites reside within this region, isoforms of RB protein from cellular lysates with various degrees of phosphorylation were compared with respect to their DNA-binding affinity. The hyperphosphorylated form was eluted from DNA-cellulose columns at...
RNA splicing generates multiple transcript isoforms from a single gene and enhances the complexit... more RNA splicing generates multiple transcript isoforms from a single gene and enhances the complexity of eukaryotic gene expression. In some eukaryotes, operon exists as an ancient regulatory mechanism of gene expression that requires strict positional and regulatory relationships among its genes. It remains unknown whether operonic genes generate transcript isoforms in a similar manner as non-operonic genes do, the expression of which is less likely limited by their positions and relationships with surrounding genes. We analyzed the number of transcript isoforms of Caenorhabditis elegans operonic genes and found that C. elegans operons contain a much higher proportion of genes with multiple transcript isoforms than non-operonic genes do. For genes that express multiple transcript isoforms, there is no apparent difference between the number of isoforms in operonic and non-operonic genes. C. elegans operonic genes also have a different preference of the 20 most common 3' splice site...
Background Mammalian genome sequence data are being acquired in large quantities and at enormous ... more Background Mammalian genome sequence data are being acquired in large quantities and at enormous speeds. We now have a tremendous opportunity to better understand which genes are the most variable or conserved, and what their particular functions and evolutionary dynamics are, through comparative genomics. Results We chose human and eleven other high-coverage mammalian genome data–as well as an avian genome as an outgroup–to analyze orthologous protein-coding genes using nonsynonymous (Ka) and synonymous (Ks) substitution rates. After evaluating eight commonly-used methods of Ka and Ks calculation, we observed that these methods yielded a nearly uniform result when estimating Ka, but not Ks (or Ka/Ks). When sorting genes based on Ka, we noticed that fast-evolving and slow-evolving genes often belonged to different functional classes, with respect to species-specificity and lineage-specificity. In particular, we identified two functional classes of genes in the acquired immune system...
Most populations now use hereditary surnames, and most societies have patrilineal surnames. This ... more Most populations now use hereditary surnames, and most societies have patrilineal surnames. This naming system is believed to have started almost 5000 years ago in China. According to legends and ancient history books, there were Eight Great Xings of High Antiquity that were the ancestors of most Chinese surnames today and are thought to be descended from the two legendary prehistoric Emperors Yan and Huang. Recent work identified three Neolithic super-grandfathers represented by Y chromosome haplotypes, O3a1c, O3a2c1, and O3a2c1a, which makes it possible to test the tales of Yan-Huang and their descendant surnames. We performed two independent surveys of contemporary Han Chinese males (total number of subjects 2415) and divided the subjects into four groups based on the relationships of their surnames with the Eight Great Xings, Jiang (Yan), Ying (Huang), Ji(Huang), and Others (5 remaining Xings related to Huang). In both studies, we found that subjects with O3a1c were enriched wit...
Mutations in mitochondrial genome have epistatic effects on organisms depending on the nuclear ba... more Mutations in mitochondrial genome have epistatic effects on organisms depending on the nuclear background, but a role for the compatibility of mitochondrial-nuclear genomes (mit-n) in the quantitative nature of a complex trait remains unexplored. We studied a panel of recombinant inbred advanced intercrossed lines (RIAILs) of C. elegans that were established from a cross between the N2 and HW strains. We determined the HW nuclear genome content and the mitochondrial type (HW or N2) of each RIAIL strain. We found that the degree of mit-n compatibility was correlated with the lifespans but not the foraging behaviors of RIAILs. Several known aging-associated QTLs individually showed no relationship with mitotypes but collectively a weak trend consistent with a role in mit-n compatibility. By association mapping, we identified 293 SNPs that showed linkage with lifespan and a relationship with mitotypes consistent with a role in mit-n compatibility. We further found an association betwee...
We studied the collective effects of single nucleotide polymorphisms (SNPs) on transgenerational ... more We studied the collective effects of single nucleotide polymorphisms (SNPs) on transgenerational inheritance in C. elegans recombinant inbred advanced intercross lines (RIAILs) and yeast segregants. We divided the RIAILs and segregants into two groups of high and low minor allele content (MAC). RIAILs with higher MAC needed less generations of benzaldehyde training to gain a stable olfactory imprint and showed a greater change from normal after benzaldehyde training. Yeast segregants with higher MAC showed a more dramatic shortening of the lag phase length after ethanol exposure. The short lag phase as acquired by ethanol training was more dramatically lost after recovery in ethanol free medium for the high MAC group. We also found a preferential association between MAC and traits linked with higher number of additive QTLs. These results suggest a role for the collective effects of SNPs in transgenerational inheritance, and may help explain human variations in disease susceptibility.
Histone methyltransferase (HMT)(1) class enzymes that methylate lysine residues of histones or pr... more Histone methyltransferase (HMT)(1) class enzymes that methylate lysine residues of histones or proteins contain a conserved catalytic core termed the SET domain, which shares sequence homology with an independently described sequence motif, the PR domain. Intact PR or SET sequence is required for tumor suppression functions, but it remains unclear whether it is histone methyltransferase activity that underlies tumor suppression. We now show that tumor suppressor RIZ1 (PRDM2) methylates histone H3 on lysine 9, and this activity is reduced by mutations in the PR domain found in human cancers. Also, S-adenosylhomocysteine or methyl donor deficiency inhibits RIZ1 and other H3 lysine 9 methylation activities. These results support the hypothesis that H3 lysine 9 methylation activities of a PR/SET domain have tumor suppression functions and may underlie carcinogenesis associated with dietary methyl donor deficiency.
RIZ1 is an estrogen receptor (ER) coactivator but is also a histone lysine methyltransferase that... more RIZ1 is an estrogen receptor (ER) coactivator but is also a histone lysine methyltransferase that methylates lysine 9 of histone H3, an activity known to repress transcription. We show here that target organs of mice deficient in RIZ1 exhibit decreased response to female sex hormones. RIZ1 interacted with SRC1 and p300, suggesting that the coactivator function of RIZ1 may be mediated by its interaction with other transcriptional coactivators. In the presence of estrogen, RIZ1 binding to estrogen target genes became less direct and followed the binding of ER to DNA and RIZ1 methyltransferase activity on H3-Lys 9 was inhibited, indicating derepression may play a role in estrogen induction of gene transcription. Reducing RIZ1 level correlated with decreased induction of pS2 gene by estrogen in MCF7 cells. The data suggest that a histone methyltransferase is required for optimal estrogen response in female reproductive tissues and that estrogen-bound ER may turn a transcriptional repres...
Analyses of Y chromosome variations of extant people have resulted in two models for the paternal... more Analyses of Y chromosome variations of extant people have resulted in two models for the paternal phylogenetic tree of modern humans with roots either in Africa or East Asia. These two trees are differentiated mainly by when and where their mega-haplogroups branched apart. This paper examines previously published Y chromosome sequencing data of 17 ancient samples to compare these two competing models. As ancient samples have had less time to evolve, they are expected to have mutated in some, but not all, of the sites that define present day haplogroups to which they belong. Indeed, most of the ancient DNAs here showed that expected pattern for both the terminal and the basal haplogroups to which they belong, all of the ones which are non-controversial or considered real by both of the two competing models followed that pattern. However, for basal haplogroups not shared by the two models, such expected pattern could be observed only if the haplogroups specific to the Asia rather than...
The process of molecular evolution has many elements that are not yet fully understood. Evolution... more The process of molecular evolution has many elements that are not yet fully understood. Evolutionary rates are known to vary among protein coding and noncoding DNAs, and most of the observed changes in amino acid or nucleotide sequences are assumed to be non-adaptive by the neutral theory of molecular evolution. However, it remains unclear whether fixed and standing missense changes in slowly evolving proteins are more or less neutral compared to those in fast evolving genes. Here, based on the evolutionary rates as inferred from identity scores between orthologs in human and Rhesus Macaques (Macaca mulatta), we found that the fraction of conservative substitutions between species was significantly higher in their slowly evolving proteins. Similar results were obtained by using four different methods of scoring conservative substitutions, including three that remove the impact of substitution probability, where conservative changes require fewer mutations. We also examined the singl...
Analyses of extant people have resulted in two models for the uniparental DNA phylogenetic trees ... more Analyses of extant people have resulted in two models for the uniparental DNA phylogenetic trees of modern humans rooted in either Africa or East Asia. The Africa model is based on the neutral theory. The Asia model is reached from the maximum genetic diversity (MGD) theory. To test the two competing theories, we examined published data of ancient uniparental DNAs. Many ancient samples belonging to a terminal haplogroup were found to have mutated only in some, but not all, of the sites that define a more basal haplogroup. This pattern was found for the non-controversial haplogroups shared by the two competing models, and also for the haplogroups specific to the Asia model. Furthermore, many ancient samples that do not belong to some of the haplogroups of the Africa model nonetheless had mutations in them, which makes it impossible to unambiguously assign them to a haplogroup within the Africa model. Finally, uniparental DNAs of archaic humans were found to carry some modern alleles ...
Over the past four decades, molecular studies have yielded two primary models for understanding t... more Over the past four decades, molecular studies have yielded two primary models for understanding the uniparental DNA phylogenetic trees of modern humans: the Out of Africa (OOA) and the Out of East Asia (OOEA) models. These models differ in their underlying assumptions, particularly in relation to early stem haplotypes, even though they share many haplotype relationships. Leveraging the wealth of new genetic variants unveiled through the comprehensive sequencing of 43 diverse human Y chromosomes, we here investigated the presence of shared variants among different haplotypes to determine which model better aligns with the genetic data. We validated our approach by confirming numerous well-established haplotype relationships that are consistent with both the OOA and OOEA models. Remarkably, our analysis revealed a compelling pattern: we were able to corroborate the existence of stem haplotypes specific to the OOEA model, but not those exclusive to the OOA model. For instance, we found...
Human genetic diversity remains to be better understood. We here analyzed data from the 1000 Geno... more Human genetic diversity remains to be better understood. We here analyzed data from the 1000 Genomes Project and defined group specific fixed alleles (GSFAs) as those that are likely fixed in one ethnic group but non-fixed in at least one other group. The fraction of derived alleles in GSFAs indicates relative distance to apes because such alleles are absent in apes. Our results show that different groups differed in GSFA numbers consistent with known genetic diversity patterns, but also differed in the fraction of derived alleles in GSFAs throughout the entire genome, with East Asians having the largest fraction, followed by South Asians, Europeans, Native Americans, and Africans. Fast evolving sites such as intergenic regions were enriched with derived alleles and showed greater differences in GSFA numbers between East Asians and Africans. Furthermore, GSFAs in East Asians are mostly not fixed in other groups especially Africans, which was particularly more pronounced for fast evo...
The RIZ (G3B/MTB-Zf) gene was first isolated based on its ability to bind to the retinoblastoma p... more The RIZ (G3B/MTB-Zf) gene was first isolated based on its ability to bind to the retinoblastoma protein (Rb). An acidic, approximately 100-amino-acid region around the Rb-binding motif of RIZ has structural and antigenic similarity to the conserved sequences of the E1A viral oncogene. We show here that this region interacts specifically with the E1A-binding domain of Rb. This interaction could be disrupted by E1A or by a peptide of RIZ homologous to the CR2 motif of E1A which is involved in binding to Rb family proteins. Also like E1A, RIZ can form a ternary complex with Rb and E2F1. Despite this similarity to E1A, however, RIZ could not bind to the Rb family proteins p107 and p130 in vitro. The data show that the RIZ CR2 motif can mediate differential binding to Rb family proteins. We also mapped the shared antigenic determinant between RIZ and E1A to a conserved sequence, designated CE1, which is located in the C terminus of E1A. Unlike that of ETA, the CE1 motif of RIZ is located...
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research, 1990
The retinoblastoma (RB) gene encodes a nuclear phosphoprotein with a molecular weight of 110,000 ... more The retinoblastoma (RB) gene encodes a nuclear phosphoprotein with a molecular weight of 110,000 (pp110RB) associated with DNA-binding activity. This sequence-nonspecific DNA binding activity was further studied by Southwestern and DNA-cellulose chromatography using purified fusion proteins expressed in Escherichia coli. Three fusion proteins, containing amino acids 612-775, 776-928, and 612-928 of pp110RB, bound to DNA; the binding affinity of the latter was approximately 20-fold higher than those of either smaller region. Other regions of pp110RB had no detectable binding activity, indicating that the carboxyl-terminal region of the RB protein is the major domain responsible for interacting with DNA. Since several potential phosphorylation sites reside within this region, isoforms of RB protein from cellular lysates with various degrees of phosphorylation were compared with respect to their DNA-binding affinity. The hyperphosphorylated form was eluted from DNA-cellulose columns at...
RNA splicing generates multiple transcript isoforms from a single gene and enhances the complexit... more RNA splicing generates multiple transcript isoforms from a single gene and enhances the complexity of eukaryotic gene expression. In some eukaryotes, operon exists as an ancient regulatory mechanism of gene expression that requires strict positional and regulatory relationships among its genes. It remains unknown whether operonic genes generate transcript isoforms in a similar manner as non-operonic genes do, the expression of which is less likely limited by their positions and relationships with surrounding genes. We analyzed the number of transcript isoforms of Caenorhabditis elegans operonic genes and found that C. elegans operons contain a much higher proportion of genes with multiple transcript isoforms than non-operonic genes do. For genes that express multiple transcript isoforms, there is no apparent difference between the number of isoforms in operonic and non-operonic genes. C. elegans operonic genes also have a different preference of the 20 most common 3' splice site...
Background Mammalian genome sequence data are being acquired in large quantities and at enormous ... more Background Mammalian genome sequence data are being acquired in large quantities and at enormous speeds. We now have a tremendous opportunity to better understand which genes are the most variable or conserved, and what their particular functions and evolutionary dynamics are, through comparative genomics. Results We chose human and eleven other high-coverage mammalian genome data–as well as an avian genome as an outgroup–to analyze orthologous protein-coding genes using nonsynonymous (Ka) and synonymous (Ks) substitution rates. After evaluating eight commonly-used methods of Ka and Ks calculation, we observed that these methods yielded a nearly uniform result when estimating Ka, but not Ks (or Ka/Ks). When sorting genes based on Ka, we noticed that fast-evolving and slow-evolving genes often belonged to different functional classes, with respect to species-specificity and lineage-specificity. In particular, we identified two functional classes of genes in the acquired immune system...
Most populations now use hereditary surnames, and most societies have patrilineal surnames. This ... more Most populations now use hereditary surnames, and most societies have patrilineal surnames. This naming system is believed to have started almost 5000 years ago in China. According to legends and ancient history books, there were Eight Great Xings of High Antiquity that were the ancestors of most Chinese surnames today and are thought to be descended from the two legendary prehistoric Emperors Yan and Huang. Recent work identified three Neolithic super-grandfathers represented by Y chromosome haplotypes, O3a1c, O3a2c1, and O3a2c1a, which makes it possible to test the tales of Yan-Huang and their descendant surnames. We performed two independent surveys of contemporary Han Chinese males (total number of subjects 2415) and divided the subjects into four groups based on the relationships of their surnames with the Eight Great Xings, Jiang (Yan), Ying (Huang), Ji(Huang), and Others (5 remaining Xings related to Huang). In both studies, we found that subjects with O3a1c were enriched wit...
Mutations in mitochondrial genome have epistatic effects on organisms depending on the nuclear ba... more Mutations in mitochondrial genome have epistatic effects on organisms depending on the nuclear background, but a role for the compatibility of mitochondrial-nuclear genomes (mit-n) in the quantitative nature of a complex trait remains unexplored. We studied a panel of recombinant inbred advanced intercrossed lines (RIAILs) of C. elegans that were established from a cross between the N2 and HW strains. We determined the HW nuclear genome content and the mitochondrial type (HW or N2) of each RIAIL strain. We found that the degree of mit-n compatibility was correlated with the lifespans but not the foraging behaviors of RIAILs. Several known aging-associated QTLs individually showed no relationship with mitotypes but collectively a weak trend consistent with a role in mit-n compatibility. By association mapping, we identified 293 SNPs that showed linkage with lifespan and a relationship with mitotypes consistent with a role in mit-n compatibility. We further found an association betwee...
We studied the collective effects of single nucleotide polymorphisms (SNPs) on transgenerational ... more We studied the collective effects of single nucleotide polymorphisms (SNPs) on transgenerational inheritance in C. elegans recombinant inbred advanced intercross lines (RIAILs) and yeast segregants. We divided the RIAILs and segregants into two groups of high and low minor allele content (MAC). RIAILs with higher MAC needed less generations of benzaldehyde training to gain a stable olfactory imprint and showed a greater change from normal after benzaldehyde training. Yeast segregants with higher MAC showed a more dramatic shortening of the lag phase length after ethanol exposure. The short lag phase as acquired by ethanol training was more dramatically lost after recovery in ethanol free medium for the high MAC group. We also found a preferential association between MAC and traits linked with higher number of additive QTLs. These results suggest a role for the collective effects of SNPs in transgenerational inheritance, and may help explain human variations in disease susceptibility.
Histone methyltransferase (HMT)(1) class enzymes that methylate lysine residues of histones or pr... more Histone methyltransferase (HMT)(1) class enzymes that methylate lysine residues of histones or proteins contain a conserved catalytic core termed the SET domain, which shares sequence homology with an independently described sequence motif, the PR domain. Intact PR or SET sequence is required for tumor suppression functions, but it remains unclear whether it is histone methyltransferase activity that underlies tumor suppression. We now show that tumor suppressor RIZ1 (PRDM2) methylates histone H3 on lysine 9, and this activity is reduced by mutations in the PR domain found in human cancers. Also, S-adenosylhomocysteine or methyl donor deficiency inhibits RIZ1 and other H3 lysine 9 methylation activities. These results support the hypothesis that H3 lysine 9 methylation activities of a PR/SET domain have tumor suppression functions and may underlie carcinogenesis associated with dietary methyl donor deficiency.
RIZ1 is an estrogen receptor (ER) coactivator but is also a histone lysine methyltransferase that... more RIZ1 is an estrogen receptor (ER) coactivator but is also a histone lysine methyltransferase that methylates lysine 9 of histone H3, an activity known to repress transcription. We show here that target organs of mice deficient in RIZ1 exhibit decreased response to female sex hormones. RIZ1 interacted with SRC1 and p300, suggesting that the coactivator function of RIZ1 may be mediated by its interaction with other transcriptional coactivators. In the presence of estrogen, RIZ1 binding to estrogen target genes became less direct and followed the binding of ER to DNA and RIZ1 methyltransferase activity on H3-Lys 9 was inhibited, indicating derepression may play a role in estrogen induction of gene transcription. Reducing RIZ1 level correlated with decreased induction of pS2 gene by estrogen in MCF7 cells. The data suggest that a histone methyltransferase is required for optimal estrogen response in female reproductive tissues and that estrogen-bound ER may turn a transcriptional repres...
Analyses of Y chromosome variations of extant people have resulted in two models for the paternal... more Analyses of Y chromosome variations of extant people have resulted in two models for the paternal phylogenetic tree of modern humans with roots either in Africa or East Asia. These two trees are differentiated mainly by when and where their mega-haplogroups branched apart. This paper examines previously published Y chromosome sequencing data of 17 ancient samples to compare these two competing models. As ancient samples have had less time to evolve, they are expected to have mutated in some, but not all, of the sites that define present day haplogroups to which they belong. Indeed, most of the ancient DNAs here showed that expected pattern for both the terminal and the basal haplogroups to which they belong, all of the ones which are non-controversial or considered real by both of the two competing models followed that pattern. However, for basal haplogroups not shared by the two models, such expected pattern could be observed only if the haplogroups specific to the Asia rather than...
The process of molecular evolution has many elements that are not yet fully understood. Evolution... more The process of molecular evolution has many elements that are not yet fully understood. Evolutionary rates are known to vary among protein coding and noncoding DNAs, and most of the observed changes in amino acid or nucleotide sequences are assumed to be non-adaptive by the neutral theory of molecular evolution. However, it remains unclear whether fixed and standing missense changes in slowly evolving proteins are more or less neutral compared to those in fast evolving genes. Here, based on the evolutionary rates as inferred from identity scores between orthologs in human and Rhesus Macaques (Macaca mulatta), we found that the fraction of conservative substitutions between species was significantly higher in their slowly evolving proteins. Similar results were obtained by using four different methods of scoring conservative substitutions, including three that remove the impact of substitution probability, where conservative changes require fewer mutations. We also examined the singl...
Analyses of extant people have resulted in two models for the uniparental DNA phylogenetic trees ... more Analyses of extant people have resulted in two models for the uniparental DNA phylogenetic trees of modern humans rooted in either Africa or East Asia. The Africa model is based on the neutral theory. The Asia model is reached from the maximum genetic diversity (MGD) theory. To test the two competing theories, we examined published data of ancient uniparental DNAs. Many ancient samples belonging to a terminal haplogroup were found to have mutated only in some, but not all, of the sites that define a more basal haplogroup. This pattern was found for the non-controversial haplogroups shared by the two competing models, and also for the haplogroups specific to the Asia model. Furthermore, many ancient samples that do not belong to some of the haplogroups of the Africa model nonetheless had mutations in them, which makes it impossible to unambiguously assign them to a haplogroup within the Africa model. Finally, uniparental DNAs of archaic humans were found to carry some modern alleles ...
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