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Arm-specific dynamics of chromosome evolution in malaria mosquitoes.

Sharakhova MV, Xia A, Leman SC, Sharakhov IV - BMC Evol. Biol. (2011)

Bottom Line: To gain a better understanding of the arm-specific differences in the rates of genome rearrangements, we compared gene orders and established syntenic relationships among Anopheles gambiae, Anopheles funestus, and Anopheles stephensi.Our results suggest that natural selection favors specific gene combinations within polymorphic inversions when distant species are exposed to similar environmental pressures.Our data support the chromosomal arm specificity in rates of gene order disruption during mosquito evolution.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Entomology, Virginia Tech, Blacksburg, VA 24061, USA.

ABSTRACT

Background: The malaria mosquito species of subgenus Cellia have rich inversion polymorphisms that correlate with environmental variables. Polymorphic inversions tend to cluster on the chromosomal arms 2R and 2L but not on X, 3R and 3L in Anopheles gambiae and homologous arms in other species. However, it is unknown whether polymorphic inversions on homologous chromosomal arms of distantly related species from subgenus Cellia nonrandomly share similar sets of genes. It is also unclear if the evolutionary breakage of inversion-poor chromosomal arms is under constraints.

Results: To gain a better understanding of the arm-specific differences in the rates of genome rearrangements, we compared gene orders and established syntenic relationships among Anopheles gambiae, Anopheles funestus, and Anopheles stephensi. We provided evidence that polymorphic inversions on the 2R arms in these three species nonrandomly captured similar sets of genes. This nonrandom distribution of genes was not only a result of preservation of ancestral gene order but also an outcome of extensive reshuffling of gene orders that created new combinations of homologous genes within independently originated polymorphic inversions. The statistical analysis of distribution of conserved gene orders demonstrated that the autosomal arms differ in their tolerance to generating evolutionary breakpoints. The fastest evolving 2R autosomal arm was enriched with gene blocks conserved between only a pair of species. In contrast, all identified syntenic blocks were preserved on the slowly evolving 3R arm of An. gambiae and on the homologous arms of An. funestus and An. stephensi.

Conclusions: Our results suggest that natural selection favors specific gene combinations within polymorphic inversions when distant species are exposed to similar environmental pressures. This knowledge could be useful for the discovery of genes responsible for an association of inversion polymorphisms with phenotypic variations in multiple species. Our data support the chromosomal arm specificity in rates of gene order disruption during mosquito evolution. We conclude that the distribution of breakpoint regions is evolutionary conserved on slowly evolving arms and tends to be lineage-specific on rapidly evolving arms.

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Polymorphic inversions on chromosome 2 of An. gambiae. The heterozygote polymorphic inversions 2Rbc (a) and 2La (b) are shown.
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Figure 6: Polymorphic inversions on chromosome 2 of An. gambiae. The heterozygote polymorphic inversions 2Rbc (a) and 2La (b) are shown.

Mentions: The presence of common genes within inversions of homologous chromosomal arms could indicate that natural selection favors certain adaptive gene combinations when different species are exposed to similar environments. We tested for the presence or absence of physically and in silico mapped cDNA and BAC clones, which contained genes, in common polymorphic inversions of three mosquito species [14,16,18,27] at ~1-Mb level of resolution (Figures 1, 2, 3 and 4). In the previous study, we performed a test on the uniformity of the marker distribution across the chromosomes in An. gambiae, An. stephensi, and An. funestus using the Χ2 statistic [11]. The distribution of the DNA markers was shown to be uniform for each arm and each species. The observed number of shared genes in polymorphic inversions of An. stephensi and An. gambiae (Additional file 4), as well as of An. funestus and An. gambiae (Additional file 5), were compared to those that would be expected under pure chance. Under the hypothesis that the genes are distributed due to pure chance with respect to polymorphic inversions and to each other, identical markers would be randomly distributed across a pair of chromosome arms from different species. Our results rejected this hypothesis as we found cases of nonrandom clustering of markers within polymorphic inversions in different species. Figure 5 shows the heat plots for the test statistic: (Oi,j - Ei,j)2/Ei,j, which demonstrate the difference between the observed and expected number of shared markers in each inversion of An. gambiae and An. stephensi, as well as An. gambiae and An. funestus. Simulated p-values were computed from Monte Carlo simulated distributions, based on our test statistic, by considering the number of simulated replicates which were larger than the observed statistics (Table 1). Additional file 6 shows the probabilities that the intensity rate exceeds one for shared genes between An. stephensi and An. gambiae. Figure 5a, b shows the corresponding intensity heat map (based on the test statistic (Oi,j - Ei,j)2/Ei,j, which aids in visually assessing the locations of shared hot and cold spots. We define γi,j as the estimated factor of increased gene sharage, over what we would expect at random (See Methods for details). Inferred values where γi,j = 1 suggest the shared polymorphism is in line with what we might expect to see at random. On the 2R arm, we observed that marker pairs 2Rf (in An. stephensi) and 2Ru (in An. gambiae) correspond to an activity hotspot (indicated by the light-yellow color in Figure 5a) with posterior probability Pr(γi,j > 1/Data) = 1. The level of increase over expectation is dramatic (6.23 times). Similarly, additional file 6, accompanied by Figure 5 c, d, details results for shared polymorphic inversions between An. funestus and An. gambiae. Again we observed on the 2R arm that marker pairs between 2Rt (in An. funestus) and 2Ru (in An. gambiae) determine a hotspot of shared polymorphisms (Pr(γi,j > 1/Data) = 1, 6.22 times). Another example of nonrandomly shared genes is the small 2Rb inversion of An. gambiae (Figure 6a) and the overlapping inversions 2Rd and 2Rh of An. funestus (Figures 1 and 5c). The large 2La inversion is the only common inversion in An. gambiae on this arm (Figure 6b). We found from little to no co-occurrence of the same markers in this inversion and polymorphic inversions on 3R of An. funestus and 3L of An. stephensi (less yellow and more orange boxes) (Figures 2 and 5b, d). The results provide evidence that several polymorphic inversions at least on the 2R arm of An. gambiae nonrandomly share gene combinations with inversions of An. stephensi and An. funestus.


Arm-specific dynamics of chromosome evolution in malaria mosquitoes.

Sharakhova MV, Xia A, Leman SC, Sharakhov IV - BMC Evol. Biol. (2011)

Polymorphic inversions on chromosome 2 of An. gambiae. The heterozygote polymorphic inversions 2Rbc (a) and 2La (b) are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3094232&req=5

Figure 6: Polymorphic inversions on chromosome 2 of An. gambiae. The heterozygote polymorphic inversions 2Rbc (a) and 2La (b) are shown.
Mentions: The presence of common genes within inversions of homologous chromosomal arms could indicate that natural selection favors certain adaptive gene combinations when different species are exposed to similar environments. We tested for the presence or absence of physically and in silico mapped cDNA and BAC clones, which contained genes, in common polymorphic inversions of three mosquito species [14,16,18,27] at ~1-Mb level of resolution (Figures 1, 2, 3 and 4). In the previous study, we performed a test on the uniformity of the marker distribution across the chromosomes in An. gambiae, An. stephensi, and An. funestus using the Χ2 statistic [11]. The distribution of the DNA markers was shown to be uniform for each arm and each species. The observed number of shared genes in polymorphic inversions of An. stephensi and An. gambiae (Additional file 4), as well as of An. funestus and An. gambiae (Additional file 5), were compared to those that would be expected under pure chance. Under the hypothesis that the genes are distributed due to pure chance with respect to polymorphic inversions and to each other, identical markers would be randomly distributed across a pair of chromosome arms from different species. Our results rejected this hypothesis as we found cases of nonrandom clustering of markers within polymorphic inversions in different species. Figure 5 shows the heat plots for the test statistic: (Oi,j - Ei,j)2/Ei,j, which demonstrate the difference between the observed and expected number of shared markers in each inversion of An. gambiae and An. stephensi, as well as An. gambiae and An. funestus. Simulated p-values were computed from Monte Carlo simulated distributions, based on our test statistic, by considering the number of simulated replicates which were larger than the observed statistics (Table 1). Additional file 6 shows the probabilities that the intensity rate exceeds one for shared genes between An. stephensi and An. gambiae. Figure 5a, b shows the corresponding intensity heat map (based on the test statistic (Oi,j - Ei,j)2/Ei,j, which aids in visually assessing the locations of shared hot and cold spots. We define γi,j as the estimated factor of increased gene sharage, over what we would expect at random (See Methods for details). Inferred values where γi,j = 1 suggest the shared polymorphism is in line with what we might expect to see at random. On the 2R arm, we observed that marker pairs 2Rf (in An. stephensi) and 2Ru (in An. gambiae) correspond to an activity hotspot (indicated by the light-yellow color in Figure 5a) with posterior probability Pr(γi,j > 1/Data) = 1. The level of increase over expectation is dramatic (6.23 times). Similarly, additional file 6, accompanied by Figure 5 c, d, details results for shared polymorphic inversions between An. funestus and An. gambiae. Again we observed on the 2R arm that marker pairs between 2Rt (in An. funestus) and 2Ru (in An. gambiae) determine a hotspot of shared polymorphisms (Pr(γi,j > 1/Data) = 1, 6.22 times). Another example of nonrandomly shared genes is the small 2Rb inversion of An. gambiae (Figure 6a) and the overlapping inversions 2Rd and 2Rh of An. funestus (Figures 1 and 5c). The large 2La inversion is the only common inversion in An. gambiae on this arm (Figure 6b). We found from little to no co-occurrence of the same markers in this inversion and polymorphic inversions on 3R of An. funestus and 3L of An. stephensi (less yellow and more orange boxes) (Figures 2 and 5b, d). The results provide evidence that several polymorphic inversions at least on the 2R arm of An. gambiae nonrandomly share gene combinations with inversions of An. stephensi and An. funestus.

Bottom Line: To gain a better understanding of the arm-specific differences in the rates of genome rearrangements, we compared gene orders and established syntenic relationships among Anopheles gambiae, Anopheles funestus, and Anopheles stephensi.Our results suggest that natural selection favors specific gene combinations within polymorphic inversions when distant species are exposed to similar environmental pressures.Our data support the chromosomal arm specificity in rates of gene order disruption during mosquito evolution.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Entomology, Virginia Tech, Blacksburg, VA 24061, USA.

ABSTRACT

Background: The malaria mosquito species of subgenus Cellia have rich inversion polymorphisms that correlate with environmental variables. Polymorphic inversions tend to cluster on the chromosomal arms 2R and 2L but not on X, 3R and 3L in Anopheles gambiae and homologous arms in other species. However, it is unknown whether polymorphic inversions on homologous chromosomal arms of distantly related species from subgenus Cellia nonrandomly share similar sets of genes. It is also unclear if the evolutionary breakage of inversion-poor chromosomal arms is under constraints.

Results: To gain a better understanding of the arm-specific differences in the rates of genome rearrangements, we compared gene orders and established syntenic relationships among Anopheles gambiae, Anopheles funestus, and Anopheles stephensi. We provided evidence that polymorphic inversions on the 2R arms in these three species nonrandomly captured similar sets of genes. This nonrandom distribution of genes was not only a result of preservation of ancestral gene order but also an outcome of extensive reshuffling of gene orders that created new combinations of homologous genes within independently originated polymorphic inversions. The statistical analysis of distribution of conserved gene orders demonstrated that the autosomal arms differ in their tolerance to generating evolutionary breakpoints. The fastest evolving 2R autosomal arm was enriched with gene blocks conserved between only a pair of species. In contrast, all identified syntenic blocks were preserved on the slowly evolving 3R arm of An. gambiae and on the homologous arms of An. funestus and An. stephensi.

Conclusions: Our results suggest that natural selection favors specific gene combinations within polymorphic inversions when distant species are exposed to similar environmental pressures. This knowledge could be useful for the discovery of genes responsible for an association of inversion polymorphisms with phenotypic variations in multiple species. Our data support the chromosomal arm specificity in rates of gene order disruption during mosquito evolution. We conclude that the distribution of breakpoint regions is evolutionary conserved on slowly evolving arms and tends to be lineage-specific on rapidly evolving arms.

Show MeSH
Related in: MedlinePlus