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Detecting evolutionary strata on the human x chromosome in the absence of gametologous y-linked sequences.

Pandey RS, Wilson Sayres MA, Azad RK - Genome Biol Evol (2013)

Bottom Line: Mammalian sex chromosomes arose from a pair of homologous autosomes that differentiated into the X and Y chromosomes following a series of recombination suppression events between the X and Y.We have developed an integrative method that combines a top-down, recursive segmentation algorithm with a bottom-up, agglomerative clustering algorithm to decipher compositionally distinct regions on the X, which reflect regions of unique X-Y divergence.The older strata, from the first up to the third stratum, have remained poorly resolved due to paucity of X-Y gametologs.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, University of North Texas.

ABSTRACT
Mammalian sex chromosomes arose from a pair of homologous autosomes that differentiated into the X and Y chromosomes following a series of recombination suppression events between the X and Y. The stepwise recombination suppressions from the distal long arm to the distal short arm of the chromosomes are reflected as regions with distinct X-Y divergence, referred to as evolutionary strata on the X. All current methods for stratum detection depend on X-Y comparisons but are severely limited by the paucity of X-Y gametologs. We have developed an integrative method that combines a top-down, recursive segmentation algorithm with a bottom-up, agglomerative clustering algorithm to decipher compositionally distinct regions on the X, which reflect regions of unique X-Y divergence. In application to human X chromosome, our method correctly classified a concatenated set of 35 previously assayed X-linked gene sequences by evolutionary strata. We then extended our analysis, applying this method to the entire sequence of the human X chromosome, in an effort to define stratum boundaries. The boundaries of more recently formed strata on X-added region, namely the fourth and fifth strata, have been defined by previous studies and are recapitulated with our method. The older strata, from the first up to the third stratum, have remained poorly resolved due to paucity of X-Y gametologs. By analyzing the entire X sequence, our method identified seven evolutionary strata in these ancient regions, where only three could previously be assayed, thus demonstrating the robustness of our method in detecting the evolutionary strata.

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Density of repetitive elements or genes across the clusters identified on the X chromosome. Here, we show the difference in the feature density between clusters: (A) density of genes, repetitive elements, CpG islands, and simple repeats is plotted for each cluster; (B) the repetitive element density is plotted for each cluster along with the L1, LTR, and Alu subsets of repetitive element.
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evt139-F3: Density of repetitive elements or genes across the clusters identified on the X chromosome. Here, we show the difference in the feature density between clusters: (A) density of genes, repetitive elements, CpG islands, and simple repeats is plotted for each cluster; (B) the repetitive element density is plotted for each cluster along with the L1, LTR, and Alu subsets of repetitive element.

Mentions: We also found that much of the compositional heterogeneity between strata on the human X chromosome can be explained by the presence of repetitive elements, because our method, when applied to the entire X chromosome with repetitive elements masked out, does not return the underlying strata structure (fig. 2). Ross et al. (2005) found that LINEs increase in frequency with increasing stratum age (at least when considering the most recent three strata) but did not observe a monotonic pattern with respect to GC content. Similarly, we do not observe a striking pattern with respect to GC content (supplementary table S1, Supplementary Material online). Further, we also observe a monotonically increasing trend in the density of repetitive elements in the strata with distance from Xpter across the entire XAR (fig. 3A). In this younger region, the stratum structure deciphered by our proposed method reinforces the earlier observation of increase in repetitive element densities after the suppression of X-Y recombination. This may also have contributed to the heterogeneity between strata. In addition, we observe that this pattern breaks down in the older strata. Across the XCR, we observe that nearly all clusters share a similarly high level of repeat density, which may be attributed to the long evolutionary time that the XCR has been without homologous X-Y recombination, resulting in saturation in the density of repetitive elements across this region. Curiously, the cluster in the XAR that spans the recently X-transposed region has a higher repeat density than the remaining clusters in the XAR, which may be due to the inclusion of the centromeric sequence. When we break down the repetitive elements into different types, we observe that L1s (more than LTRs and Alus) account for the bulk of the variation in the density of repetitive elements between clusters (fig. 3B).Fig. 3.—


Detecting evolutionary strata on the human x chromosome in the absence of gametologous y-linked sequences.

Pandey RS, Wilson Sayres MA, Azad RK - Genome Biol Evol (2013)

Density of repetitive elements or genes across the clusters identified on the X chromosome. Here, we show the difference in the feature density between clusters: (A) density of genes, repetitive elements, CpG islands, and simple repeats is plotted for each cluster; (B) the repetitive element density is plotted for each cluster along with the L1, LTR, and Alu subsets of repetitive element.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814197&req=5

evt139-F3: Density of repetitive elements or genes across the clusters identified on the X chromosome. Here, we show the difference in the feature density between clusters: (A) density of genes, repetitive elements, CpG islands, and simple repeats is plotted for each cluster; (B) the repetitive element density is plotted for each cluster along with the L1, LTR, and Alu subsets of repetitive element.
Mentions: We also found that much of the compositional heterogeneity between strata on the human X chromosome can be explained by the presence of repetitive elements, because our method, when applied to the entire X chromosome with repetitive elements masked out, does not return the underlying strata structure (fig. 2). Ross et al. (2005) found that LINEs increase in frequency with increasing stratum age (at least when considering the most recent three strata) but did not observe a monotonic pattern with respect to GC content. Similarly, we do not observe a striking pattern with respect to GC content (supplementary table S1, Supplementary Material online). Further, we also observe a monotonically increasing trend in the density of repetitive elements in the strata with distance from Xpter across the entire XAR (fig. 3A). In this younger region, the stratum structure deciphered by our proposed method reinforces the earlier observation of increase in repetitive element densities after the suppression of X-Y recombination. This may also have contributed to the heterogeneity between strata. In addition, we observe that this pattern breaks down in the older strata. Across the XCR, we observe that nearly all clusters share a similarly high level of repeat density, which may be attributed to the long evolutionary time that the XCR has been without homologous X-Y recombination, resulting in saturation in the density of repetitive elements across this region. Curiously, the cluster in the XAR that spans the recently X-transposed region has a higher repeat density than the remaining clusters in the XAR, which may be due to the inclusion of the centromeric sequence. When we break down the repetitive elements into different types, we observe that L1s (more than LTRs and Alus) account for the bulk of the variation in the density of repetitive elements between clusters (fig. 3B).Fig. 3.—

Bottom Line: Mammalian sex chromosomes arose from a pair of homologous autosomes that differentiated into the X and Y chromosomes following a series of recombination suppression events between the X and Y.We have developed an integrative method that combines a top-down, recursive segmentation algorithm with a bottom-up, agglomerative clustering algorithm to decipher compositionally distinct regions on the X, which reflect regions of unique X-Y divergence.The older strata, from the first up to the third stratum, have remained poorly resolved due to paucity of X-Y gametologs.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, University of North Texas.

ABSTRACT
Mammalian sex chromosomes arose from a pair of homologous autosomes that differentiated into the X and Y chromosomes following a series of recombination suppression events between the X and Y. The stepwise recombination suppressions from the distal long arm to the distal short arm of the chromosomes are reflected as regions with distinct X-Y divergence, referred to as evolutionary strata on the X. All current methods for stratum detection depend on X-Y comparisons but are severely limited by the paucity of X-Y gametologs. We have developed an integrative method that combines a top-down, recursive segmentation algorithm with a bottom-up, agglomerative clustering algorithm to decipher compositionally distinct regions on the X, which reflect regions of unique X-Y divergence. In application to human X chromosome, our method correctly classified a concatenated set of 35 previously assayed X-linked gene sequences by evolutionary strata. We then extended our analysis, applying this method to the entire sequence of the human X chromosome, in an effort to define stratum boundaries. The boundaries of more recently formed strata on X-added region, namely the fourth and fifth strata, have been defined by previous studies and are recapitulated with our method. The older strata, from the first up to the third stratum, have remained poorly resolved due to paucity of X-Y gametologs. By analyzing the entire X sequence, our method identified seven evolutionary strata in these ancient regions, where only three could previously be assayed, thus demonstrating the robustness of our method in detecting the evolutionary strata.

Show MeSH
Related in: MedlinePlus