X-chromosome contributes more SVs under positive selection
The population genetic theory predicts that positive Darwinian selection
can drive the standing or de novo mutations to sweep through a
population, to achieve diverse local adaptations and develop novel
phenotypes [71]. To understand the influence of positive selection
on the evolutionary fate of SVs, we inferred the regions under positive
selection for the Chinese and Indian rhesus macaques. Based on
population genetics, positive selection would hallmark several features
along chromosomes, including but not limited to, the increased fixation
index (FST ) between focal population and control
population, the reduced nucleotide diversity (π) in focal population
relative to control population, and the elevated expected haplotype
homozygosity [72-74]. The selective sweep signals were estimated
based on three complementary methods including the ratio of nucleotide
diversity between Indian and Chinese populations
(θ π_India/θ π_China), the
fixation index (FST ), and the haplotype
homozygosity (Ihh12) (Figure 5A-C).
Totally, we identified 1400 genes under selective sweep for the two
subspecies, with 164 genes for the Chinese and 1236 genes for Indian
rhesus macaques (Supplementary table 3). Notably, over 38% of
positively selected genes were distributed in X chromosome,
significantly higher than the expected average level of autosomes (the
Χ² test, p < 0.00001). The strongest signal in the Chinese
group was found in an autosome gene TTC28 (Figure 5B), which is
related to human developmental disease based on human exome sequencing
of fetal anomaly syndromes [75]. For Indian rhesus macaques, the
highest signal was found in an X-chromosome gene, IL1RAPL2(Figure 5C), which is involved in diseases including mental development
and autism [76, 77]. The gene function enrichment analysis revealed
that the most significant pathways involve the Guanyl-nucleotide
exchange factor activity and regulation of cell projection organization,
for the Chinese (Figure 5D) and Indian rhesus macaques (Figure 5E),
respectively.
Interesting, we found that the two genes with the strongest signals
among all positively selected genes, IL1RAPL2 and TTC28 ,
were involved in intragenic SVs (insertions and deletions, Supplementary
table 4). Thus, it is very interesting to know whether SVs could be
driven by the evolutionary force of positive selection in rhesus
macaques. We found that, among the 2248 congruent SVs shared by three
methods, 3.20% of SVs (72/2248) showed signals of selective sweep in
intergenic and intragenic DNA regions (Supplementary table 5). Moreover,
3.79% of positively selected genes (53/1400) were detected with signals
of congruent SVs (Supplementary table 6). Interestingly, X chromosome
exhibited a significant higher contribution (26.45%, 14/53) to the
positively selected genes involved in SVs than autosomes (the Χ² test, p
< 0.00001; Figure 5F). The regression analysis revealed the
positively selected SVs in autosomes do not follow a simple linear model
against the overall congruent SVs (p = 0.4, Figure 5F). However, the X
chromosome exhibited as an obvious outlier with excess number of
positively selected SVs (Figure 5G). These findings suggest that SVs
could serve as an important raw material for natural selection to
operate on genomic diversity.