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Alix Sayuri Souza Katsuyama
Iderval da Silva Jr. Sobrinho
Unidade Acadêmica Especial de
Ciências Biológicas,
Universidade Federal de Jataí.
alixsayuri@outlook.com
Introduction
The CENP-A has important functions for
cell division because it provides stability
of centromeric chromatin and functions
as a tag to identify centromere. It
directly interacts with two proteins,
CENP-C and CENP-N to initiate the
formation of the kinetochore.
CENP-A substitutes a non-
centromeric paralogous histone H3 in
centromeres and shares some
nucleotide sequence with H3.
Considering that disruption in the
assemblage of kinetochore would
impair meiosis, we would expect
CENP-A to be a conserved protein due
to its central role in initiating
kinetochore assemblage.
However, comparisons of CENP-A sequences
from different lineages have revealed that this
protein had evolved at high evolutionary rate,
unlike histone H3, which is relatively conserved
along its evolutionary history.
The coevolution of CENP-A with the other two
proteins (CENP-C and CENP-N) could be an
explanation for its high evolutionary rate.
We aimed to test the hypothesis of coevolution between CENP-A and CENP-N as the driven force
that had speed up their evolution.
We expect that both proteins would have similar evolutionary rates if a process of coevolution had
occurred between them.
Considering that changes in one protein would favor changes in another protein in a coevolutionary
context, we expect to find signals of positive selection in both.
Materials & Methods
Nucleotide sequences
search
Alignment Evolutinary model and
Phylogeny reconstruction
Substitution
saturation test
Branch-site
test of natural
selection
Nucleotide divergence
DAMBEPAML
Results
Species B. taurus R. novergivus M. musculus G. gallus
B. taurus 0.000 0.264 0.392 0.378
R. novergivus - 0.000 0.248 0.378
M. musculus - - 0.000 0.692
G. gallus - - - 0.000
Species B. taurus R. novergivus M. musculus G. gallus
B. taurus 0.000 0.198 0,200 0.332
R. novergivus - 0.000 0.097 0.374
M. musculus - - 0.000 0.391
G. gallus - - - 0.000
Table 1. CENP-A nucleotide divergence among different
vertebrate lineages. Nubers highlighted in orange indicate
greater differences in nucleotide divergence between CENP-A
and CENP-N in same lineage comparisons.
0%
20%
40%
60%
80%
100%
1
5
9
13
17
21
25
29
33
37
41
45
49
53
57
61
65
69
73
77
81
85
89
93
97
Purifying selection Neutrality
0%
20%
40%
60%
80%
100%
1
13
25
37
49
61
73
85
97
109
121
133
145
157
169
181
193
205
217
229
241
253
265
277
289
301
313
325
Purifying selection Neutrality
Figure 1. Relative probability of a site (codon) to be under
purifying selection or neutrality as estimated by Branch-site test.
A) Probabilities in CENP-A; B) Probabilities in CENP-N. No sites
under positive selection were detected in both proteins.
A)
B)
Table 2. CENP-N nucleotide divergence among different
vertebrate lineages. Nubers highlighted in orange indicate
greater differences in nucleotide divergence between CENP-A
and CENP-N in same lineage comparisons.
Codon
RelativeProbabilityRelativeProbability
Codon
Discussion & conclusions
A C K N O W L E D G M E N T S
Similarity in evolutionary rates between CENP-
A and CENP-N and positive selection signals in
both proteins could be the two major expected
evidences whether a coevolution had occurred
between both proteins. However, ours results
do not support both expectations, indicating
that a coevolutionary process could not explain
the high evolutionary rates found in CENP-A
Our results from Branch-site test (Figure 1 A
and B) and from comparison of nucleotide
divergence (Table 1 and 2) confirmed that
CENP-A is less conserved than CENP-N.
However, such higher evolutionary rate could
not be explained by positive selection, but by a
higher proportion of sites evolving under
neutrality if compared with CENP-N.

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Does centromeric CENP-A coevolve with an interacting kinetochore CENP-N?

  • 1. Alix Sayuri Souza Katsuyama Iderval da Silva Jr. Sobrinho Unidade Acadêmica Especial de Ciências Biológicas, Universidade Federal de Jataí. alixsayuri@outlook.com
  • 2. Introduction The CENP-A has important functions for cell division because it provides stability of centromeric chromatin and functions as a tag to identify centromere. It directly interacts with two proteins, CENP-C and CENP-N to initiate the formation of the kinetochore. CENP-A substitutes a non- centromeric paralogous histone H3 in centromeres and shares some nucleotide sequence with H3. Considering that disruption in the assemblage of kinetochore would impair meiosis, we would expect CENP-A to be a conserved protein due to its central role in initiating kinetochore assemblage. However, comparisons of CENP-A sequences from different lineages have revealed that this protein had evolved at high evolutionary rate, unlike histone H3, which is relatively conserved along its evolutionary history. The coevolution of CENP-A with the other two proteins (CENP-C and CENP-N) could be an explanation for its high evolutionary rate. We aimed to test the hypothesis of coevolution between CENP-A and CENP-N as the driven force that had speed up their evolution. We expect that both proteins would have similar evolutionary rates if a process of coevolution had occurred between them. Considering that changes in one protein would favor changes in another protein in a coevolutionary context, we expect to find signals of positive selection in both.
  • 3. Materials & Methods Nucleotide sequences search Alignment Evolutinary model and Phylogeny reconstruction Substitution saturation test Branch-site test of natural selection Nucleotide divergence DAMBEPAML
  • 4. Results Species B. taurus R. novergivus M. musculus G. gallus B. taurus 0.000 0.264 0.392 0.378 R. novergivus - 0.000 0.248 0.378 M. musculus - - 0.000 0.692 G. gallus - - - 0.000 Species B. taurus R. novergivus M. musculus G. gallus B. taurus 0.000 0.198 0,200 0.332 R. novergivus - 0.000 0.097 0.374 M. musculus - - 0.000 0.391 G. gallus - - - 0.000 Table 1. CENP-A nucleotide divergence among different vertebrate lineages. Nubers highlighted in orange indicate greater differences in nucleotide divergence between CENP-A and CENP-N in same lineage comparisons. 0% 20% 40% 60% 80% 100% 1 5 9 13 17 21 25 29 33 37 41 45 49 53 57 61 65 69 73 77 81 85 89 93 97 Purifying selection Neutrality 0% 20% 40% 60% 80% 100% 1 13 25 37 49 61 73 85 97 109 121 133 145 157 169 181 193 205 217 229 241 253 265 277 289 301 313 325 Purifying selection Neutrality Figure 1. Relative probability of a site (codon) to be under purifying selection or neutrality as estimated by Branch-site test. A) Probabilities in CENP-A; B) Probabilities in CENP-N. No sites under positive selection were detected in both proteins. A) B) Table 2. CENP-N nucleotide divergence among different vertebrate lineages. Nubers highlighted in orange indicate greater differences in nucleotide divergence between CENP-A and CENP-N in same lineage comparisons. Codon RelativeProbabilityRelativeProbability Codon
  • 5. Discussion & conclusions A C K N O W L E D G M E N T S Similarity in evolutionary rates between CENP- A and CENP-N and positive selection signals in both proteins could be the two major expected evidences whether a coevolution had occurred between both proteins. However, ours results do not support both expectations, indicating that a coevolutionary process could not explain the high evolutionary rates found in CENP-A Our results from Branch-site test (Figure 1 A and B) and from comparison of nucleotide divergence (Table 1 and 2) confirmed that CENP-A is less conserved than CENP-N. However, such higher evolutionary rate could not be explained by positive selection, but by a higher proportion of sites evolving under neutrality if compared with CENP-N.