Comparative population genomic analysis uncovers novel genomic footprints and genes associated with small body size in Chinese pony

- Comparative population genomic analysis uncovers novel genomic footprints and genes associated with small body size in Chinese pony.
- Background: Body size is considered as one of the most fundamental properties of an organism.
- Debao pony (DBP), a famous Chinese horse, is known for its small body size and lives in Guangxi mountains of southern China.
- In this study, we employed comparative population genomics to study the genetic basis underlying the small body size of DBP breed based on the whole genome sequencing data.
- and further analyzed the results to find genomic regions under selection for body size-related traits..
- The most significant signal of positive selection was mapped to the NELL1 gene, probably underlies the body size and development traits, and may also have been selected for short stature in the DBP population.
- In addition, some other loci on different chromosomes were identified to be potentially involved in the development of body size..
- Conclusions: Results of our study identified some positively selected genes across the horse genome, which are possibly involved in body size traits.
- understanding of the molecular basis of body size and as such they should be of great interest for future research into the genetic architecture of relevant traits in horse breeding program..
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- 32 Jiaochang Donglu, Kunming, Yunnan, China Full list of author information is available at the end of the article.
- For thousands of years, enormous variety of domestic breeds with different morphological, physiological and behavioral characters have been domesticated and raised in different parts of the world.
- Due to intensive breeding and artificial selection throughout the domestication history, horses exhibit strik- ing variation of height at withers and body size.
- Today, body size is one of the most important criteria for the evaluation and classification of different breeds, and also is an essential parameter for breeding programmers to im- prove marketability and performance [4].
- There are several pony breeds in the world, though varying in body size, skin color and geographic origins, all of them share some basic traits that make them different from other horse breeds.
- Debao pony (DBP), a famous Chinese horse breed, is known for its small body size and lives in Guangxi mountains of southern China.
- DBPs ex- hibit peculiar morphoanatomical adaptation to facilitate work in the mountainous regions, for example their average adult height is around 94 cm and 98 cm for male and females, respectively [8, 9]..
- In the present study, whole genome sequencing (WGS) data were used for comparative population gen- omics to identify the genetic basis underlying the small stature of DBP..
- The topological pattern found in the tree was also supported by both PCA (Fig.
- Based on the results obtained from phylogenetic analysis and to avoid bias from unequal sample sizes, we com- pared the whole genome of DBP individuals, as a pony- sized (genetically homogeneous) breed with Thorough- bred (THB) horses, as a large well-defined (genetically homogeneous) breed, to identify signatures of positive selection related to body size traits.
- protein-coding genes were identified in the top 1% win- dows with high F ST values (Additional file 1: Table S3)..
- Gene set en- richment analysis (GSEA) identified some significantly enriched categories related with skeletal development, such as “broad hallux” (HP broad phalanges of the hand” (HP:0009768) and “broad toe” (HP:.
- For these ex- treme values, some enriched gene ontology (GO) terms were found to be related with skeletal development cat- egories, including “aplasia/hypoplasia of the tibia” (HP:.
- A total of 681 candidate genes were identified in the top percentiles of approach (1% cutoff) (Additional file 1: Table S7).
- Before to the application of methods for detecting signa- tures of selection, we first assessed the phylogeny of the horse breeds to evaluate the phylogenetic position of DBP within the species.
- racing per- formance, in the breeding programs [42] while DBPs clearly have an ancient origin following a long-term nat- ural selection.
- Also, discovering the ROH per each breed showed the lower level of ROH in the DBP population compared to other horses.
- ROH for THB population, that is concordant with previ- ous study in the six different horse breeds [43]..
- Potential independent of positive selection in the DBP population.
- Because of the small body size of DBP, that is notably less than average horse breeds, we focused specifically on the loci that may play more important roles in the rapid evolution of body size during the domestication process.
- In our broad spectrum analysis, several previously reported genes were found to be probably involved in body size related traits.
- BMP2, a bone formation-related gene, was found as one of the candidates on ECA5.
- Previous studies have found associ- ations of the BMP-2 variants with bone and cardiac de- velopment, bone mineral density, as well as body size.
- Another possible candidate gene, FGFR1, was found in one of the selection regions on ECA27 (top 1% cutoff for Fst and log2 θπ ratio values) (Fig.
- Considering the im- portant function of FGFR1 in skeletal development, this gene is an important candidate for body size variation in mammalians..
- Table 1 Candidate genes putatively selected by three statistical methods ( F ST , log 2 θπ ratio and XP-CLR) affecting body size traits in DBP.
- ARPP21 16 ENSECAG Body size traits [31].
- PLXDC2 29 ENSECAG Body size traits [39].
- Body size is recognized as one of the most fundamen- tal properties of an organism, affecting nearly all bio- logical aspects.
- In the last decades, new insights from the genetic and physiological studies have refined our understanding of genetic basis of body size, as the target of positive selection in human and domesticated ani- mals.
- Human body size is a polygenic trait affected by variants of numerous genes and their interactions with environmental factors.
- In contrast, sev- eral independent studies in domesticated animals have shown that changes in body size can be controlled by a few genes with large effects.
- For instance, it has been demonstrated that one specific haplotype defined by 20 SNPs spanning the recent selection sweep covering IGF- 1 gene has a major effect on body size within all small dogs [49].
- A similar study has shown that one SNP within the strong linkage region of BMP10 gene ex- plained around 22% of the overall body weight variance in five chicken lines [2].
- Also, one study on dairy and beef cattle revealed the variation in the average height can be controlled by only 10 genes in eight genomic re- gions [50]..
- Based on the standard additive model, Makvandi- Nejad et al.
- Using the same dataset of these 48 horses, a recent GWAS study involving both dominant and recessive mixed- model approaches as well as a genome-wide scan for sig- natures of selection based on the F ST genetic differenti- ation and XP-CLR test, ANKRD1 gene was identified and validated as a novel candidate, explaining 7.98% of the genetic variance in body size of the American Mini- ature horse (AMH).
- Compared with the fixed status of all four loci identified by Makvandi-Nejad et al.
- In other in- dependent studies, the differential SNPs in LCORL gene on ECA ZFAT gene on ECA9 [51], TBX3 gene on ECA8 [9] and LASP1 gene on ECA11 [55] have also been shown to be strongly associated with body size traits in horses..
- In this study, we have investigated the genetic basis underlying the body size variation in DBP.
- In our broad spectrum of analyses by three methods, we did not find any significant selection signal within or near genes which were previously identified as horse body size- related candidates.
- Instead, we observe that NELL1 gene likely played an important role in the evolution of the small stature of DBP, an ancient small pony that was evolved in the mountainous areas in southwestern China.
- In this study, using next-generation sequencing analysis, we identified some novel candidate genes under selec- tion for body size traits in DBP population.
- These novel candidate genes may be useful target for clarifying our understanding of the molecular basis of body size and they should be of great interest for fu- ture research addressing the genetic architecture of rele- vant traits in horse breeding program..
- The sample size for our experiment was calculated based on Ma et al., guidelines [56].
- Ma et al., (2015) showed that a reasonable power to detect selection sig- natures is achieved with high marker density (>.
- High-quality reads in the present study and published data were aligned against the horse reference genome, ENSEMBL (version 94) (ftp://ftp.ensembl.org/pub/re- lease-94/fasta/equus_caballus/dna.
- We then im- proved alignment accuracy by minimize such mismatch- ing bases using RealignerTargetCreator, IndelRealigner, and BaseRecalibrator functions in the Genome Analysis Toolkit (GATK .
- Identification of candidate genes under positive selection in the DBP.
- Three different statistic methods were used to identify regions of the genome that have the highest signals of selective sweeps in DBPs.
- Sliding window analyses were performed upon a window size of 50 kb and a step size of 25 kb across of the genome.
- We additionally per- formed XP-CLR test to detect regions in the genome where the change in allele frequency at the locus almost-occurred recently.
- The regions with the XP-CLR values in the top 0.01 of the empirical distribution were designated as signal of positive selection..
- To search the possible pathways involved in the regions with top values ( F ST , log2 θπ ratio and XP-CLR), candi- date selective regions were annotated using the Variant Effect Predictor available at (http://asia.ensembl.org/.
- And the P -value of the gene enrichment was corrected by Benjamini–Hochberg FDR (false discovery rate)..
- This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA National Natural Science Foundation of China the Sino-Africa Joint Research Center, Chin- ese Academy of Sciences (SAJC201611), and Research Center for Ecology and Environment of Central Asia, Chinese Academy of Sciences.
- Samples used in this study were provided by the Animal Branch of the Germplasm Bank of Wild Species, Chinese Acad- emy of Sciences (the Large Research Infrastructure Funding)..
- This study was funded by Strategic Priority Research Program of the Chinese Academy of Sciences (XDA National Natural Science Foundation of China the Sino-Africa Joint Research Center, Chinese Academy of Sciences (SAJC201611), and Research Center for Ecology and Environment of Central Asia, Chinese Academy of Sciences.
- The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript..
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- defining complex traits of body size and shape.
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