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Prevalence of multinucleotide replacements in evolution of primates and Drosophila.

Terekhanova NV, Bazykin GA, Neverov A, Kondrashov AS, Seplyarskiy VB - Mol. Biol. Evol. (2013)

Bottom Line: The plurality of MNRs affect nearby nucleotides, so that at least six times as many DNRs affect two adjacent nucleotide sites than sites 10 nucleotides apart.Still, approximately 60% of DNRs, and approximately 90% of TNRs, span distances more than two (or three) nucleotides.The prevalence of MNRs matches that is observed in data on de novo mutations and is also observed in the regions with the lowest sequence conservation, suggesting that MNRs mainly have mutational origin; however, epistatic selection and/or gene conversion may also play a role.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia.

ABSTRACT
Evolution of sequences mostly involves independent changes at different sites. However, substitutions at neighboring sites may co-occur as multinucleotide replacement events (MNRs). Here, we compare noncoding sequences of several species of primates, and of three species of Drosophila fruit flies, in a phylogenetic analysis of the replacements that occurred between species at nearby nucleotide sites. Both in primates and in Drosophila, the frequency of single-nucleotide replacements is substantially elevated within 10 nucleotides from other replacements that occurred on the same lineage but not on another lineage. The data imply that dinucleotide replacements (DNRs) affecting sites at distances of up to 10 nucleotides from each other are responsible for 2.3% of single-nucleotide replacements in primate genomes and for 5.6% in Drosophila genomes. Among these DNRs, 26% and 69%, respectively, are in fact parts of replacements of three or more trinucleotide replacements (TNRs). The plurality of MNRs affect nearby nucleotides, so that at least six times as many DNRs affect two adjacent nucleotide sites than sites 10 nucleotides apart. Still, approximately 60% of DNRs, and approximately 90% of TNRs, span distances more than two (or three) nucleotides. MNRs make a major contribution to the observed clustering of substitutions: In the human-chimpanzee comparison, DNRs are responsible for 50% of cases when two nearby replacements are observed on the human lineage, and TNRs are responsible for 83% of cases when three replacements at three immediately adjacent sites are observed on the human lineage. The prevalence of MNRs matches that is observed in data on de novo mutations and is also observed in the regions with the lowest sequence conservation, suggesting that MNRs mainly have mutational origin; however, epistatic selection and/or gene conversion may also play a role.

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Frequencies of DNRs in D. melanogaster–D. simulans comparison for different distances between sites. (A–C) dd(k) (red), sd(k) (blue), and αd(k) (green) are shown for distances  between the sites (horizontal axis). (A) Introns; (B) intergenic regions; and (C) positions 8–30 in introns with lengths up to 120 nucleotides. (D) αd(k) for all intronic sites (gray) and positions 8–30 in introns with lengths up to 120 nucleotides (orange) plotted together. The differences between the two curves are insignificant for all k. Error bars for αd(k) correspond to 95% confidence intervals obtained by 1,000 bootstrap simulations; for data from all intronic sites and intergenic regions, they are not shown because they would be barely visible.
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mst036-F6: Frequencies of DNRs in D. melanogaster–D. simulans comparison for different distances between sites. (A–C) dd(k) (red), sd(k) (blue), and αd(k) (green) are shown for distances between the sites (horizontal axis). (A) Introns; (B) intergenic regions; and (C) positions 8–30 in introns with lengths up to 120 nucleotides. (D) αd(k) for all intronic sites (gray) and positions 8–30 in introns with lengths up to 120 nucleotides (orange) plotted together. The differences between the two curves are insignificant for all k. Error bars for αd(k) correspond to 95% confidence intervals obtained by 1,000 bootstrap simulations; for data from all intronic sites and intergenic regions, they are not shown because they would be barely visible.

Mentions: In contrast to primates, in Drosophila, even a substitution that occurs on the proxy lineage substantially increases the frequency of nearby substitutions on the D. melanogaster lineage (figs. 6 and 7, red lines). This effect spans distances of tens of nucleotides and is consistent with pervasive short-scale heterogeneity of the substitution rate in Drosophila (Seplyarskiy et al. 2012).Fig. 6.


Prevalence of multinucleotide replacements in evolution of primates and Drosophila.

Terekhanova NV, Bazykin GA, Neverov A, Kondrashov AS, Seplyarskiy VB - Mol. Biol. Evol. (2013)

Frequencies of DNRs in D. melanogaster–D. simulans comparison for different distances between sites. (A–C) dd(k) (red), sd(k) (blue), and αd(k) (green) are shown for distances  between the sites (horizontal axis). (A) Introns; (B) intergenic regions; and (C) positions 8–30 in introns with lengths up to 120 nucleotides. (D) αd(k) for all intronic sites (gray) and positions 8–30 in introns with lengths up to 120 nucleotides (orange) plotted together. The differences between the two curves are insignificant for all k. Error bars for αd(k) correspond to 95% confidence intervals obtained by 1,000 bootstrap simulations; for data from all intronic sites and intergenic regions, they are not shown because they would be barely visible.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3649671&req=5

mst036-F6: Frequencies of DNRs in D. melanogaster–D. simulans comparison for different distances between sites. (A–C) dd(k) (red), sd(k) (blue), and αd(k) (green) are shown for distances between the sites (horizontal axis). (A) Introns; (B) intergenic regions; and (C) positions 8–30 in introns with lengths up to 120 nucleotides. (D) αd(k) for all intronic sites (gray) and positions 8–30 in introns with lengths up to 120 nucleotides (orange) plotted together. The differences between the two curves are insignificant for all k. Error bars for αd(k) correspond to 95% confidence intervals obtained by 1,000 bootstrap simulations; for data from all intronic sites and intergenic regions, they are not shown because they would be barely visible.
Mentions: In contrast to primates, in Drosophila, even a substitution that occurs on the proxy lineage substantially increases the frequency of nearby substitutions on the D. melanogaster lineage (figs. 6 and 7, red lines). This effect spans distances of tens of nucleotides and is consistent with pervasive short-scale heterogeneity of the substitution rate in Drosophila (Seplyarskiy et al. 2012).Fig. 6.

Bottom Line: The plurality of MNRs affect nearby nucleotides, so that at least six times as many DNRs affect two adjacent nucleotide sites than sites 10 nucleotides apart.Still, approximately 60% of DNRs, and approximately 90% of TNRs, span distances more than two (or three) nucleotides.The prevalence of MNRs matches that is observed in data on de novo mutations and is also observed in the regions with the lowest sequence conservation, suggesting that MNRs mainly have mutational origin; however, epistatic selection and/or gene conversion may also play a role.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia.

ABSTRACT
Evolution of sequences mostly involves independent changes at different sites. However, substitutions at neighboring sites may co-occur as multinucleotide replacement events (MNRs). Here, we compare noncoding sequences of several species of primates, and of three species of Drosophila fruit flies, in a phylogenetic analysis of the replacements that occurred between species at nearby nucleotide sites. Both in primates and in Drosophila, the frequency of single-nucleotide replacements is substantially elevated within 10 nucleotides from other replacements that occurred on the same lineage but not on another lineage. The data imply that dinucleotide replacements (DNRs) affecting sites at distances of up to 10 nucleotides from each other are responsible for 2.3% of single-nucleotide replacements in primate genomes and for 5.6% in Drosophila genomes. Among these DNRs, 26% and 69%, respectively, are in fact parts of replacements of three or more trinucleotide replacements (TNRs). The plurality of MNRs affect nearby nucleotides, so that at least six times as many DNRs affect two adjacent nucleotide sites than sites 10 nucleotides apart. Still, approximately 60% of DNRs, and approximately 90% of TNRs, span distances more than two (or three) nucleotides. MNRs make a major contribution to the observed clustering of substitutions: In the human-chimpanzee comparison, DNRs are responsible for 50% of cases when two nearby replacements are observed on the human lineage, and TNRs are responsible for 83% of cases when three replacements at three immediately adjacent sites are observed on the human lineage. The prevalence of MNRs matches that is observed in data on de novo mutations and is also observed in the regions with the lowest sequence conservation, suggesting that MNRs mainly have mutational origin; however, epistatic selection and/or gene conversion may also play a role.

Show MeSH
Related in: MedlinePlus