Skip to main content
Log in

Genome-wide investigation of microsatellite polymorphism in coding region of the giant panda (Ailuropoda melanoleuca) genome: a resource for study of phenotype diversity and abnormal traits

  • Original Paper
  • Published:
Mammal Research Aims and scope Submit manuscript

Abstract

Repeat number variations of coding simple sequence repeats (coding SSRs) generate phenotype diversity for environmental adaptation and rapid adaptive evolution. Despite the positive potential of coding SSR mutations, the repeat variations have also been shown to cause hereditary disorders and severe diseases. However, there have been few reports on the analysis of SSR polymorphism in genome-wide coding regions. We identified 1016 coding SSRs, of which 283 SSRs (27.9%) were polymorphic with 2 to 8 alleles, using 33 re-sequenced giant panda genomes. The 283 polymorphic coding SSRs were mapped on 260 genes, which were assigned into 547 GO terms. Functional analysis of 260 genes showed that four significantly enriched pathways: thyroid hormone signaling pathway, pancreatic secretion, gastric acid secretion, and thyroid hormone synthesis, were relevant to digestion and metabolism. The comparison analysis of gene functions exhibited positive regulation of transcription, DNA-templated term (GO:0045893), the poly(A) RNA-binding term (GO:0008270), and zinc ion–binding term (GO:0044822) which were only significantly enriched in genes containing polymorphic coding SSRs. This indicates coding SSR polymorphism may be involved in binding and regulation functions that can affect the expression of their downstream genes and contribute to diverse phenotypes. Our results provide a solid foundation for further study regarding the effect of coding SSR polymorphism on the adaptation, adaptive evolution, and abnormal traits of the giant panda.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Ackermann M, Chao L (2006) DNA sequences shaped by selection for stability. PLoS Genet 2:e22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aravind L, Iyer LM, Koonin EV (2006) Comparative genomics and structural biology of the molecular innovations of eukaryotes. Curr Opin Struct Biol 16:409–419

    Article  CAS  PubMed  Google Scholar 

  • Bichara M, Wagner J, Lambert IB (2006) Mechanisms of tandem repeat instability in bacteria. Mutat Res 598:144–163

    Article  CAS  PubMed  Google Scholar 

  • Bolger AM, Lohse M, Usadel B (2014) Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30:2114–2120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang DK, Metzgar D, Wills C, Boland CR (2001) Microsatellites in the eukaryotic DNA mismatch repair genes as modulators of evolutionary mutation rate. Genome Res 11:1145–1146

    Article  CAS  PubMed  Google Scholar 

  • Choubtum L, Witoonpanich P, Kulkantrakorn K, Hanchaiphiboolkul S, Pongpakdee S, Tiamkao S, Pulkes T (2016) Trinucleotide repeat expansion of TATA-binding protein gene associated with Parkinson’s disease: a Thai multicenter study. Parkinsonism Relat Disord 28:146–149

    Article  PubMed  Google Scholar 

  • Du L, Zhang C, Liu Q, Zhang X, Yue B, Hancock J (2018) Krait: an ultrafast tool for genome-wide survey of microsatellites and primer design. Bioinformatics 34:681–683

    Article  CAS  PubMed  Google Scholar 

  • Fondon JW III, Garner HR (2004) Molecular origins of rapid and continuous morphological evolution. Proc Natl Acad Sci U S A 101:18058–18063

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gaspar ML, Meo T, Bourgarel P, Guenet JL, Tosi M (1991) A single base deletion in the Tfm androgen receptor gene creates a short-lived messenger RNA that directs internal translation initiation. Proc Natl Acad Sci U S A 88:8606–8610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gemayel R, Vinces MD, Legendre M, Verstrepen KJ (2010) Variable tandem repeats accelerate evolution of coding and regulatory sequences. Annu Rev Genet 44:445–477

    Article  CAS  PubMed  Google Scholar 

  • Gymrek M, Golan D, Rosset S, Erlich Y (2012) lobSTR: a short tandem repeat profiler for personal genomes. Genome Res 22:1154–1162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hammock EA, Young LJ (2004) Functional microsatellite polymorphism associated with divergent social structure in vole species. Mol Biol Evol 21:1057–1063

    Article  CAS  PubMed  Google Scholar 

  • Hammock EA, Young LJ (2005) Microsatellite instability generates diversity in brain and sociobehavioral traits. Science 308:1630–1634

    Article  CAS  PubMed  Google Scholar 

  • Hancock JM, Simon M (2005) Simple sequence repeats in proteins and their significance for network evolution. Gene 345:113–118

    Article  CAS  PubMed  Google Scholar 

  • Holterhus PM, Bruggenwirth HT, Hiort O, Kleinkauf-Houcken A, Kruse K, Sinnecker GH, Brinkmann AO (1997) Mosaicism due to a somatic mutation of the androgen receptor gene determines phenotype in androgen insensitivity syndrome. J Clin Endocrinol Metab 82:3584–3589

    CAS  PubMed  Google Scholar 

  • Huang da W, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57

    Article  CAS  PubMed  Google Scholar 

  • Huang J, Li YZ, Du LM et al (2015) Genome-wide survey and analysis of microsatellites in giant panda (Ailuropoda melanoleuca), with a focus on the applications of a novel microsatellite marker system. BMC Genomics 16:61

    Article  PubMed  PubMed Central  Google Scholar 

  • Huang H, Yie S, Liu Y, Wang C, Cai Z, Zhang W, Lan J, Huang X, Luo L, Cai K, Hou R, Zhang Z (2016) Dietary resources shape the adaptive changes of cyanide detoxification function in giant panda (Ailuropoda melanoleuca). Sci Rep 6:34700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kashi Y, King DG (2006) Simple sequence repeats as advantageous mutators in evolution. Trends Genet 22:253–259

    Article  CAS  PubMed  Google Scholar 

  • Kim MS, Jeong EG, Ahn CH, Kim SS, Lee SH, Yoo NJ (2008) Frameshift mutation of UVRAG, an autophagy-related gene, in gastric carcinomas with microsatellite instability. Hum Pathol 39:1059–1063

    Article  CAS  PubMed  Google Scholar 

  • Kim JY, Kim SY, Kim JM, Kim YK, Yoon KY, Kim JY, Lee BC, Kim JS, Paek SH, Park SS, Kim SE, Jeon BS (2009) Spinocerebellar ataxia type 17 mutation as a causative and susceptibility gene in parkinsonism. Neurology 72:1385–1389

    Article  CAS  PubMed  Google Scholar 

  • Koga R, Yamamoto M, Ciftci HI, Otsuka M, Fujita M (2018) Introduction of H2C2-type zinc-binding residues into HIV-2 Vpr increases its expression level. FEBS Open Biol 8:146–153

    Article  CAS  Google Scholar 

  • Kurz C, Hakimi M, Kloor M et al (2015) Coding microsatellite frameshift mutations accumulate in atherosclerotic carotid artery lesions: evaluation of 26 cases and literature review. Mol Med. https://doi.org/10.2119/molmed.2014.00258

  • Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R, 1000 Genome Project Data Processing Subgroup (2009) The sequence alignment/map format and SAMtools. Bioinformatics 25:2078–2079. https://doi.org/10.1093/bioinformatics/btp352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li R, Fan W, Tian G et al (2010) The sequence and de novo assembly of the giant panda genome. Nature 463:311–317

    Article  CAS  PubMed  Google Scholar 

  • Love RA, Parge HE, Wickersham JA, Hostomsky Z, Habuka N, Moomaw EW, Adachi T, Hostomska Z (1996) The crystal structure of hepatitis C virus NS3 proteinase reveals a trypsin-like fold and a structural zinc binding site. Cell 87:331–342

    Article  CAS  PubMed  Google Scholar 

  • Maiuri T, Mocle AJ, Hung CL, Xia J, van Roon-Mom WM, Truant R (2017) Huntingtin is a scaffolding protein in the ATM oxidative DNA damage response complex Hum Mol Genet 26:395–406

  • Mar Alba M, Santibanez-Koref MF, Hancock JM (1999) Amino acid reiterations in yeast are overrepresented in particular classes of proteins and show evidence of a slippage-like mutational process. J Mol Evol 49:789–797

    Article  CAS  PubMed  Google Scholar 

  • Marmol I, Sanchez-de-Diego C, Pradilla Dieste A, Cerrada E, Rodriguez Yoldi MJ (2017) Colorectal carcinoma: a general overview and future perspectives in colorectal cancer. Int J Mol Sci. https://doi.org/10.3390/ijms18010197

  • Massey TH, Jones L (2018) The central role of DNA damage and repair in CAG repeat diseases. Dis Model Mech 11:dmm031930

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Metzgar D, Bytof J, Wills C (2000) Selection against frameshift mutations limits microsatellite expansion in coding DNA. Genome Res 10:72–80

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mirkin SM (2007) Expandable DNA repeats and human disease. Nature 447:932–940

    Article  CAS  PubMed  Google Scholar 

  • O'Dushlaine CT, Edwards RJ, Park SD, Shields DC (2005) Tandem repeat copy-number variation in protein-coding regions of human genes. Genome Biol 6:R69

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peng R, Liu Y, Cai Z, Shen F, Chen J, Hou R, Zou F (2018) Characterization and analysis of whole transcriptome of giant panda spleens: implying critical roles of long non-coding RNAs in immunity. Cell Physiol Biochem 46:1065–1077

    Article  CAS  PubMed  Google Scholar 

  • Piao Z, Fang W, Malkhosyan S, Kim H, Horii A, Perucho M, Huang S (2000) Frequent frameshift mutations of RIZ in sporadic gastrointestinal and endometrial carcinomas with microsatellite instability. Cancer Res 60:4701–4704

    CAS  PubMed  Google Scholar 

  • Quilez J, Guilmatre A, Garg P, Highnam G, Gymrek M, Erlich Y, Joshi RS, Mittelman D, Sharp AJ (2016) Polymorphic tandem repeats within gene promoters act as modifiers of gene expression and DNA methylation in humans. Nucleic Acids Res 44:3750–3762

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rockman MV, Hahn MW, Soranzo N, Loisel DA, Goldstein DB, Wray GA (2004) Positive selection on MMP3 regulation has shaped heart disease risk. Curr Biol 14:1531–1539

    Article  CAS  PubMed  Google Scholar 

  • Russell RD, Beckenbach AT (2008) Recoding of translation in turtle mitochondrial genomes: programmed frameshift mutations and evidence of a modified genetic code. J Mol Evol 67:682–695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sawyer LA, Hennessy JM, Peixoto AA, Rosato E, Parkinson H, Costa R, Kyriacou CP (1997) Natural variation in a Drosophila clock gene and temperature compensation. Science 278:2117–2120

    Article  CAS  PubMed  Google Scholar 

  • Shan L, Hu Y, Zhu L, Yan L, Wang C, Li D, Jin X, Zhang C, Wei F (2014) Large-scale genetic survey provides insights into the captive management and reintroduction of giant pandas. Mol Biol Evol 31:2663–2671

    Article  CAS  PubMed  Google Scholar 

  • Shen F, Zhang Z, He W et al (2009) Microsatellite variability reveals the necessity for genetic input from wild giant pandas (Ailuropoda melanoleuca) into the captive population. Mol Ecol 18:1061–1070

    Article  CAS  PubMed  Google Scholar 

  • Shi C, Washington K (2012) Molecular testing in colorectal cancer: diagnosis of Lynch syndrome and personalized cancer medicine. Am J Clin Pathol 137:847–859

    Article  CAS  PubMed  Google Scholar 

  • Song X, Shen F, Huang J, Huang Y, du L, Wang C, Fan Z, Hou R, Yue B, Zhang X (2016) Transcriptome-derived tetranucleotide microsatellites and their associated genes from the giant panda (Ailuropoda melanoleuca). J Hered 107:423–430

    Article  CAS  PubMed  Google Scholar 

  • Subramanian S, Mishra RK, Singh L (2003) Genome-wide analysis of microsatellite repeats in humans: their abundance and density in specific genomic regions. Genome Biol 4:R13

    Article  PubMed  PubMed Central  Google Scholar 

  • Toth G, Gaspari Z, Jurka J (2000) Microsatellites in different eukaryotic genomes: survey and analysis. Genome Res 10:967–981

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Verstrepen KJ, Jansen A, Lewitter F, Fink GR (2005) Intragenic tandem repeats generate functional variability. Nat Genet 37:986–990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vinces MD, Legendre M, Caldara M, Hagihara M, Verstrepen KJ (2009) Unstable tandem repeats in promoters confer transcriptional evolvability. Science 324:1213–1216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Q, Zhang X, Wang X, Zeng B, Jia X, Hou R, Yue B (2012) Polymorphism of CAG repeats in androgen receptor of carnivores. Mol Biol Rep 39:2297–2303

    Article  CAS  PubMed  Google Scholar 

  • Wei F, Swaisgood R, Hu Y, Nie Y, Yan L, Zhang Z, Qi D, Zhu L (2015a) Progress in the ecology and conservation of giant pandas. Conserv Biol 29:1497–1507

    Article  PubMed  Google Scholar 

  • Wei F, Wang X, Wu Q (2015b) The giant panda gut microbiome. Trends Microbiol 23:450–452

    Article  CAS  PubMed  Google Scholar 

  • Wren JD, Forgacs E, Fondon JW III et al (2000) Repeat polymorphisms within gene regions: phenotypic and evolutionary implications. Am J Hum Genet 67:345–356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu H, Zhan XJ, Zhang ZJ, Zhu LF, Yan L, Li M, Wei FW (2009) Thirty-three microsatellite loci for noninvasive genetic studies of the giant panda (Ailuropoda melanoleuca). Conserv Genet 10:649–652. https://doi.org/10.1007/s10592-008-9599-9

    Article  CAS  Google Scholar 

  • Xiao H, Yu Z, Wu Y, Nan J, Merry DE, Sekiguchi JM, Ferguson DO, Lieberman AP, Dressler GR (2012) A polyglutamine expansion disease protein sequesters PTIP to attenuate DNA repair and increase genomic instability. Hum Mol Genet 21:4225–4236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu Z, Gutierrez L, Hitchens M, Scherer S, Sater AK, Wells DE (2008) Distribution of polymorphic and non-polymorphic microsatellite repeats in Xenopus tropicalis. Bioinform Biol Insights 2:157–169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan C, Mou B, Meng Y, Tu F, Fan Z, Price M, Yue B, Zhang X (2017) A novel mitochondrial genome of Arborophila and new insight into Arborophila evolutionary history. PLoS One 12:e0181649

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ye J, Zhang Y, Cui H, Liu J, Wu Y, Cheng Y, Xu H, Huang X, Li S, Zhou A, Zhang X, Bolund L, Chen Q, Wang J, Yang H, Fang L, Shi C (2018) WEGO 2.0: a web tool for analyzing and plotting GO annotations, 2018 update. Nucleic Acids Res 46:W71–w75

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu F, Sabeti PC, Hardenbol P et al (2005) Positive selection of a pre-expansion CAG repeat of the human SCA2 gene. PLoS Genet 1:e41

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zamorzaeva I, Rashkovetsky E, Nevo E, Korol A (2005) Sequence polymorphism of candidate behavioural genes in Drosophila melanogaster flies from ‘Evolution canyon’. Mol Ecol 14:3235–3245

    Article  CAS  PubMed  Google Scholar 

  • Zeinalian M, Hashemzadeh-Chaleshtori M, Salehi R, Emami MH (2018) Clinical aspects of microsatellite instability testing in colorectal cancer. Adv Biomed Res 7:28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang W, Liu W, Hou R, Zhang L, Schmitz-Esser S, Sun H, Xie J, Zhang Y, Wang C, Li L, Yue B, Huang H, Wang H, Shen F, Zhang Z (2018) Age-associated microbiome shows the giant panda lives on hemicelluloses, not on cellulose. ISME J 12:1319–1328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao S, Zheng P, Dong S, Zhan X, Wu Q, Guo X, Hu Y, He W, Zhang S, Fan W, Zhu L, Li D, Zhang X, Chen Q, Zhang H, Zhang Z, Jin X, Zhang J, Yang H, Wang J, Wang J, Wei F (2013) Whole-genome sequencing of giant pandas provides insights into demographic history and local adaptation. Nat Genet 45:67–71

    Article  CAS  PubMed  Google Scholar 

  • Zhu L, Wu Q, Dai J, Zhang S, Wei F (2011) Evidence of cellulose metabolism by the giant panda gut microbiome. Proc Natl Acad Sci U S A 108:17714–17719

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We appreciate Dr. Lianming Du, Sanxu Liu, Yang Geng, and Chuang Zhou for their good suggestions in data analysis.

Funding

This work was funded by the National Natural Science Foundation of China (31570534) and partly funded by the State Forestry Administration (GH201709).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xiuyue Zhang.

Additional information

Communicated by: Cino Pertoldi

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(PDF 364 kb)

ESM 2

(XLSX 112 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cheng, M., Ren, J., Shen, F. et al. Genome-wide investigation of microsatellite polymorphism in coding region of the giant panda (Ailuropoda melanoleuca) genome: a resource for study of phenotype diversity and abnormal traits. Mamm Res 64, 353–363 (2019). https://doi.org/10.1007/s13364-019-00418-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13364-019-00418-5

Keywords

Navigation