165
Continuing Evolution of Xenopus Genome
FIGURE 10.3 (Continued)
XLA3L is not complete as indicated by double slashes. (B) nodal3 cluster. (C) vg1 cluster. The derrière gene is unidentifed on XLA1L
due to the incomplete genomic sequence (double slashes with a question mark). (D) ventx cluster. (E) mix/bix cluster. The same region
in teleosts and chicken are similar to HSA without gene expansions (see Watanabe et al., 2017). R005123 and R005124 of N. parkeri are
similar to mix1/mixer and bix genes, respectively. (F) siamois (sia) cluster. sia1 and sia2 are also known by the names siamois and twin,
respectively. LOC-1 and LOC-2 stand for LOC100490626 and LOC100490281, respectively.
Source: Panels are modifed from: A (Session et al., 2016); B and C (Suzuki et al., 2017a); D and E (Watanabe et al., 2017); and F (Haramoto et al., 2017).
brought about an increase in gene dose but not functional
diversity. These features are reminiscent of the rDNA
cluster (see previously), which maintains high gene doses
by homogenization through gene conversion (Hori et al.,
2021) and is located only in XLA3L, not S. Because tandemly repeated genes tend to increase or decrease in number
due to uneven crossovers during meiosis, it may be easier to
maintain an appropriate gene dose at a single locus.
10.3.3.2. Ventx, mix/bix, and siamois Clusters
Gene clusters were not always deleted from subgenome
S, as already shown for the Hox clusters, which consist of different types of paralogous genes, not as in the
nodal clusters. Therefore, it is possible to assume that
subfunctionalization of the expanded genes in the cluster may be the reason for retaining full sets (or close to
full sets) on both L and S chromosomes in X. laevis, as
shown in Figure 10.3D, E and F. The ventx cluster in X.
tropicalis contains six genes, whereas in X. laevis, the
six genes were doubled and maintained with orthologous
relationships between subgenomes L and S except for
ventx2.1/2.2 (see the following for details) and pseudogenized ventx3.1p.L (Figure 10.3D) ( Watanabe et al., 2017).
Because another frog, Nanorana parkeri (Tibetan frog)
(Sun et al., 2015), has three orthologous genes, ventx1,
ventx2, and ventx3a/3b, the ventx genes were expanded
and subfunctionalized possibly in the frog lineage or
earlier (Watanabe et al., 2017). In the common ancestor
of Xenopus, ventx1, ventx2, and ventx3 were tandemly
duplicated and rearranged. Curiously, after duplication,
ventx2.1 and ventx2.2 were presumably homogenized by
gene conversion in each cluster of X. tropicalis and X. laevis (see Supplementary Figure 18 in Watanabe et al., 2017)
and could be designated as ventx2.e1 and vent2.e2 ( Figure
10.3D). Two of the ventx genes in X. laevis, Xvent-1 and
Xvent-2 (now identifed as ventx1.2.S and ventx2.1.L,
respectively), have been described to have signif cant differences in their responses to BMP4 (Dosch et al., 1997 ),
suggesting that ventx1 and ventx2 are subfunctionalized.
X. laevis Xvex-1 (ventx3.2.S), which is again involved in
BMP4 signaling (Shapira et al., 1999), also seems to be
subfunctionalized. This is because the similarity of the
homeodomain and entire region of Xvex-1 to either those
of Xvent-1 or Xvent-2 is much lower than between these
latter two (Shapira et al., 1999; Watanabe et al., 2017).
The mix/bix cluster is similar to the ventx cluster (Figure
10.3E). Previously, the mesodermal/endodermal genes mix1,
mixer, and bix were individually identifed and analyzed in
different studies (see references in Watanabe et al., 2017), but
those genes were found to form a single gene cluster each in
subgenomes L and S (see Figure 3d and Extended Data Figure
7a in Session et al., 2016; Watanabe et al., 2017). That there
is only one mix/bix ortholog in humans and teleosts suggests
Xenopus- or frog-specifc gene expansions (Figure 10.3E)
(Watanabe et al., 2017). In the common ancestor of Xenopus,
mix1, mixer, and bix were subfunctionalized, and bix was
tandemly expanded. Similar to ventx2.1 and ventx2.2, bix
genes were likely homogenized by gene conversion in each
cluster (see Extended Figure 7a in Session et al., 2016).
In the siamois gene cluster, sia1, sia2, sia3, and sia4
were expanded (Figure 10.3F) (Haramoto et al., 2017) and
subfunctionalized (Laurent et al., 1997 ) in the common
ancestor of Xenopus. In X. laevis, after allotetraploidization, the homeologous relationships between the four paralogs in the clusters are maintained between subgenomes L
and S, though one gene in each cluster was pseudogenized
(Haramoto et al., 2017).
These data of ventx, mix/bix, and siamois gene clusters,
along with the Hox clusters, suggest that the retainment of
multiple tandemly repeated genes in both the L and S subgenomes is likely due to the genes having different roles. The
data also suggest that these gene clusters consisting of tandemly repeated subfunctionalized paralogs are much more
conserved between the L and S subgenomes compared to
those consisting of functionally equivalent genes only in the
L subgenome, such as rDNA, nodal5, nodal3, and vg1.
Thus, there are two patterns of evolutional changes of
gene clusters between the subgenomes after allotetraploidization in X. laevis. First, tandemly repeated equivalent genes
that increase gene dose may have to be kept at an optimal
level in a single locus. Second, the gene clusters that consist of subfunctionalized paralogs appear to maintain them
between L and S. This may be because there is some coordination of gene expression between gene clusters, requiring the whole region containing the cluster to be conserved.
These hypotheses remain to be tested.
10.4. CONCLUSIONS
WGD is considered one of the driving forces of evolution.
Especially, allopolyploidization occurs through hybridization coupled with WGD, which could generate a new species with heterosis by combining two different genomes
from parental species. During evolution, multiple genome
duplications have occurred in different lineages of Xenopus,
leading to speciation (see Figure 10.1A ). In general, evolution
Continuing Evolution of Xenopus Genome
FIGURE 10.3 (Continued)
XLA3L is not complete as indicated by double slashes. (B) nodal3 cluster. (C) vg1 cluster. The derrière gene is unidentifed on XLA1L
due to the incomplete genomic sequence (double slashes with a question mark). (D) ventx cluster. (E) mix/bix cluster. The same region
in teleosts and chicken are similar to HSA without gene expansions (see Watanabe et al., 2017). R005123 and R005124 of N. parkeri are
similar to mix1/mixer and bix genes, respectively. (F) siamois (sia) cluster. sia1 and sia2 are also known by the names siamois and twin,
respectively. LOC-1 and LOC-2 stand for LOC100490626 and LOC100490281, respectively.
Source: Panels are modifed from: A (Session et al., 2016); B and C (Suzuki et al., 2017a); D and E (Watanabe et al., 2017); and F (Haramoto et al., 2017).
brought about an increase in gene dose but not functional
diversity. These features are reminiscent of the rDNA
cluster (see previously), which maintains high gene doses
by homogenization through gene conversion (Hori et al.,
2021) and is located only in XLA3L, not S. Because tandemly repeated genes tend to increase or decrease in number
due to uneven crossovers during meiosis, it may be easier to
maintain an appropriate gene dose at a single locus.
10.3.3.2. Ventx, mix/bix, and siamois Clusters
Gene clusters were not always deleted from subgenome
S, as already shown for the Hox clusters, which consist of different types of paralogous genes, not as in the
nodal clusters. Therefore, it is possible to assume that
subfunctionalization of the expanded genes in the cluster may be the reason for retaining full sets (or close to
full sets) on both L and S chromosomes in X. laevis, as
shown in Figure 10.3D, E and F. The ventx cluster in X.
tropicalis contains six genes, whereas in X. laevis, the
six genes were doubled and maintained with orthologous
relationships between subgenomes L and S except for
ventx2.1/2.2 (see the following for details) and pseudogenized ventx3.1p.L (Figure 10.3D) ( Watanabe et al., 2017).
Because another frog, Nanorana parkeri (Tibetan frog)
(Sun et al., 2015), has three orthologous genes, ventx1,
ventx2, and ventx3a/3b, the ventx genes were expanded
and subfunctionalized possibly in the frog lineage or
earlier (Watanabe et al., 2017). In the common ancestor
of Xenopus, ventx1, ventx2, and ventx3 were tandemly
duplicated and rearranged. Curiously, after duplication,
ventx2.1 and ventx2.2 were presumably homogenized by
gene conversion in each cluster of X. tropicalis and X. laevis (see Supplementary Figure 18 in Watanabe et al., 2017)
and could be designated as ventx2.e1 and vent2.e2 ( Figure
10.3D). Two of the ventx genes in X. laevis, Xvent-1 and
Xvent-2 (now identifed as ventx1.2.S and ventx2.1.L,
respectively), have been described to have signif cant differences in their responses to BMP4 (Dosch et al., 1997 ),
suggesting that ventx1 and ventx2 are subfunctionalized.
X. laevis Xvex-1 (ventx3.2.S), which is again involved in
BMP4 signaling (Shapira et al., 1999), also seems to be
subfunctionalized. This is because the similarity of the
homeodomain and entire region of Xvex-1 to either those
of Xvent-1 or Xvent-2 is much lower than between these
latter two (Shapira et al., 1999; Watanabe et al., 2017).
The mix/bix cluster is similar to the ventx cluster (Figure
10.3E). Previously, the mesodermal/endodermal genes mix1,
mixer, and bix were individually identifed and analyzed in
different studies (see references in Watanabe et al., 2017), but
those genes were found to form a single gene cluster each in
subgenomes L and S (see Figure 3d and Extended Data Figure
7a in Session et al., 2016; Watanabe et al., 2017). That there
is only one mix/bix ortholog in humans and teleosts suggests
Xenopus- or frog-specifc gene expansions (Figure 10.3E)
(Watanabe et al., 2017). In the common ancestor of Xenopus,
mix1, mixer, and bix were subfunctionalized, and bix was
tandemly expanded. Similar to ventx2.1 and ventx2.2, bix
genes were likely homogenized by gene conversion in each
cluster (see Extended Figure 7a in Session et al., 2016).
In the siamois gene cluster, sia1, sia2, sia3, and sia4
were expanded (Figure 10.3F) (Haramoto et al., 2017) and
subfunctionalized (Laurent et al., 1997 ) in the common
ancestor of Xenopus. In X. laevis, after allotetraploidization, the homeologous relationships between the four paralogs in the clusters are maintained between subgenomes L
and S, though one gene in each cluster was pseudogenized
(Haramoto et al., 2017).
These data of ventx, mix/bix, and siamois gene clusters,
along with the Hox clusters, suggest that the retainment of
multiple tandemly repeated genes in both the L and S subgenomes is likely due to the genes having different roles. The
data also suggest that these gene clusters consisting of tandemly repeated subfunctionalized paralogs are much more
conserved between the L and S subgenomes compared to
those consisting of functionally equivalent genes only in the
L subgenome, such as rDNA, nodal5, nodal3, and vg1.
Thus, there are two patterns of evolutional changes of
gene clusters between the subgenomes after allotetraploidization in X. laevis. First, tandemly repeated equivalent genes
that increase gene dose may have to be kept at an optimal
level in a single locus. Second, the gene clusters that consist of subfunctionalized paralogs appear to maintain them
between L and S. This may be because there is some coordination of gene expression between gene clusters, requiring the whole region containing the cluster to be conserved.
These hypotheses remain to be tested.
10.4. CONCLUSIONS
WGD is considered one of the driving forces of evolution.
Especially, allopolyploidization occurs through hybridization coupled with WGD, which could generate a new species with heterosis by combining two different genomes
from parental species. During evolution, multiple genome
duplications have occurred in different lineages of Xenopus,
leading to speciation (see Figure 10.1A ). In general, evolution