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One pedigree we all may have come from – did Adam and Eve have the chromosome 2 fusion?

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ABSTRACT

Background: In contrast to Great Apes, who have 48 chromosomes, modern humans and likely Neandertals and Denisovans have and had, respectively, 46 chromosomes. The reduction in chromosome number was caused by the head-to-head fusion of two ancestral chromosomes to form human chromosome 2 (HSA2) and may have contributed to the reproductive barrier with Great Apes.

Results: Next generation sequencing and molecular clock analyses estimated that this fusion arose prior to our last common ancestor with Neandertal and Denisovan hominins ~ 0.74 - 4.5 million years ago.

Hypotheses: I propose that, unlike recurrent Robertsonian translocations in humans, the HSA2 fusion was a single nonrecurrent event that spread through a small polygamous clan population bottleneck. Its heterozygous to homozygous conversion, fixation, and accumulation in the succeeding populations was likely facilitated by an evolutionary advantage through the genomic loss rather than deregulation of expression of the gene(s) flanking the HSA2 fusion site at 2q13.

Conclusions: The origin of HSA2 might have been a critical evolutionary event influencing higher cognitive functions in various early subspecies of hominins. Next generation sequencing of Homo heidelbergensis and Homo erectus genomes and complete reconstruction of DNA sequence of the orthologous subtelomeric chromosomes in Great Apes should enable more precise timing of HSA2 formation and better understanding of its evolutionary consequences.

No MeSH data available.


Alignment of G-banded human (HSA2) and chimpanzee (PTR12 and PTR13) metaphase chromosomes demonstrates that a few megabases of subtelomeric regions (mainly repetitive satellite DNA) are absent in the human genome. DNA seqeunece of these genomic regions in PTR12 and PTR13 is not well annotated and their gene content is essentially unknown. Note that this sequence may not represent the deleted fragments of the ancestral chromosomes IIp and IIq [16]
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Fig1: Alignment of G-banded human (HSA2) and chimpanzee (PTR12 and PTR13) metaphase chromosomes demonstrates that a few megabases of subtelomeric regions (mainly repetitive satellite DNA) are absent in the human genome. DNA seqeunece of these genomic regions in PTR12 and PTR13 is not well annotated and their gene content is essentially unknown. Note that this sequence may not represent the deleted fragments of the ancestral chromosomes IIp and IIq [16]

Mentions: The HSA2 fusion site was first mapped using FISH within the telomeric repetitive sequences corresponding to the short arms of orthologous chimpanzee chromosomes PTR12 and PTR13 [11, 12]. Fan et al. analyzed the low-copy repeat (LCR)-rich complex genomic structure and gene content of the ~ 600 kb region surrounding the fusion site at 2q13 and mapped the chromosome junction within degenerate telomeric arrays in an intron of the non-coding DDX11L2 (DEAD/H-box helicase 11 like 2) transcript [13, 14]. Of note, the fusion site is resistant to PCR amplification and cloning. Genome-wide comparisons of recent chimpanzee and human LCRs revealed a 40 kb genomic fragment that map to four regions in the human genome, but is represented 400 times (‘hyperexpansion’) within the chimpanzee genome [15]. It was proposed that amplification of this interval occurred prior to HSA2 fusion and LCRs located close to the ancestral fusion sites might have facilitated the rearrangement between the closely flanking telomeric repeats of the two ancestral chromosomes. More recently, Ventura et al. [16] proposed a molecular-evolutionary model in which an ancestral human chimpanzee pericentric inversion and HSA2 fusion both predisposed and protected the chimpanzee and human genomes, respectively, to the formation of subtelomeric heterochromatin. Importantly, chromosome alignments, including positions of the active and vestigial [17] centromeres, as well as the current genome assemblies of HSA2, PTR12, and PTR13 chromosomes indicate that a few megabases of mostly repetitive satellite-rich subtelomeric DNA have been lost on both ancestral chromosomes (referred to as IIp and IIq) during the formation of HSA2 (Fig. 1).Fig. 1


One pedigree we all may have come from – did Adam and Eve have the chromosome 2 fusion?
Alignment of G-banded human (HSA2) and chimpanzee (PTR12 and PTR13) metaphase chromosomes demonstrates that a few megabases of subtelomeric regions (mainly repetitive satellite DNA) are absent in the human genome. DNA seqeunece of these genomic regions in PTR12 and PTR13 is not well annotated and their gene content is essentially unknown. Note that this sequence may not represent the deleted fragments of the ancestral chromosomes IIp and IIq [16]
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC5037601&req=5

Fig1: Alignment of G-banded human (HSA2) and chimpanzee (PTR12 and PTR13) metaphase chromosomes demonstrates that a few megabases of subtelomeric regions (mainly repetitive satellite DNA) are absent in the human genome. DNA seqeunece of these genomic regions in PTR12 and PTR13 is not well annotated and their gene content is essentially unknown. Note that this sequence may not represent the deleted fragments of the ancestral chromosomes IIp and IIq [16]
Mentions: The HSA2 fusion site was first mapped using FISH within the telomeric repetitive sequences corresponding to the short arms of orthologous chimpanzee chromosomes PTR12 and PTR13 [11, 12]. Fan et al. analyzed the low-copy repeat (LCR)-rich complex genomic structure and gene content of the ~ 600 kb region surrounding the fusion site at 2q13 and mapped the chromosome junction within degenerate telomeric arrays in an intron of the non-coding DDX11L2 (DEAD/H-box helicase 11 like 2) transcript [13, 14]. Of note, the fusion site is resistant to PCR amplification and cloning. Genome-wide comparisons of recent chimpanzee and human LCRs revealed a 40 kb genomic fragment that map to four regions in the human genome, but is represented 400 times (‘hyperexpansion’) within the chimpanzee genome [15]. It was proposed that amplification of this interval occurred prior to HSA2 fusion and LCRs located close to the ancestral fusion sites might have facilitated the rearrangement between the closely flanking telomeric repeats of the two ancestral chromosomes. More recently, Ventura et al. [16] proposed a molecular-evolutionary model in which an ancestral human chimpanzee pericentric inversion and HSA2 fusion both predisposed and protected the chimpanzee and human genomes, respectively, to the formation of subtelomeric heterochromatin. Importantly, chromosome alignments, including positions of the active and vestigial [17] centromeres, as well as the current genome assemblies of HSA2, PTR12, and PTR13 chromosomes indicate that a few megabases of mostly repetitive satellite-rich subtelomeric DNA have been lost on both ancestral chromosomes (referred to as IIp and IIq) during the formation of HSA2 (Fig. 1).Fig. 1

View Article: PubMed Central - PubMed

ABSTRACT

Background: In contrast to Great Apes, who have 48 chromosomes, modern humans and likely Neandertals and Denisovans have and had, respectively, 46 chromosomes. The reduction in chromosome number was caused by the head-to-head fusion of two ancestral chromosomes to form human chromosome 2 (HSA2) and may have contributed to the reproductive barrier with Great Apes.

Results: Next generation sequencing and molecular clock analyses estimated that this fusion arose prior to our last common ancestor with Neandertal and Denisovan hominins ~ 0.74 - 4.5 million years ago.

Hypotheses: I propose that, unlike recurrent Robertsonian translocations in humans, the HSA2 fusion was a single nonrecurrent event that spread through a small polygamous clan population bottleneck. Its heterozygous to homozygous conversion, fixation, and accumulation in the succeeding populations was likely facilitated by an evolutionary advantage through the genomic loss rather than deregulation of expression of the gene(s) flanking the HSA2 fusion site at 2q13.

Conclusions: The origin of HSA2 might have been a critical evolutionary event influencing higher cognitive functions in various early subspecies of hominins. Next generation sequencing of Homo heidelbergensis and Homo erectus genomes and complete reconstruction of DNA sequence of the orthologous subtelomeric chromosomes in Great Apes should enable more precise timing of HSA2 formation and better understanding of its evolutionary consequences.

No MeSH data available.