Myostatin, a member of the transforming growth factor-β (TGF-β) superfamily, has been shown to be a negative regulator of myogenesis. Here we show that myostatin functions by controlling the proliferation of muscle precursor cells. When C2C12 myoblasts were incubated with myostatin, proliferation of myoblasts decreased with increasing levels of myostatin. Fluorescence-activated cell sorting analysis revealed that myostatin prevented the progression of myoblasts from the G1- to S-phase of the cell cycle. Western analysis indicated that myostatin specifically up-regulated p21Waf1, Cip1, a cyclin-dependent kinase inhibitor, and decreased the levels and activity of Cdk2 protein in myoblasts. Furthermore, we also observed that in myoblasts treated with myostatin protein, Rb was predominately present in the hypophosphorylated form. These results suggests that, in response to myostatin signaling, there is an increase in p21 expression and a decrease in Cdk2 protein and activity thus resulting in an accumulation of hypophosphorylated Rb protein. This, in turn, leads to the arrest of myoblasts in G1-phase of cell cycle. Thus, we propose that the generalized muscular hyperplasia phenotype observed in animals that lack functional myostatin could be as a result of deregulated myoblast proliferation.

Myostatin, a negative regulator of muscle growth, functions by inhibiting myoblast proliferation.

Y Chromosome Uncovers the Recent Oriental Origin of Modern Stallions

The horse was domesticated only 5.5 KYA, thousands of years after dogs, cattle, pigs, sheep, and goats. The horse nonetheless represents the domestic animal that most impacted human history; providing us with rapid transportation, which has considerably changed the speed and magnitude of the circulation of goods and people, as well as their cultures and diseases. By revolutionizing warfare and agriculture, horses also deeply influenced the politico-economic trajectory of human societies. Reciprocally, human activities have circled back on the recent evolution of the horse, by creating hundreds of domestic breeds through selective programs, while leading all wild populations to near extinction. Despite being tightly associated with humans, several aspects in the evolution of the domestic horse remain controversial. Here, we review recent advances in comparative genomics and paleogenomics that helped advance our understanding of the genetic foundation of domestic horses.

https://www.genetics.org/content/genetics/204/2/423.full.pdf

The Evolutionary Origin and Genetic Makeup of Domestic Horses

The domesticated horse has played a unique role in human history, serving not just as a source of animal protein, but also as a catalyst for long-distance migration and military conquest. As a result, the horse developed unique physiological adaptations to meet the demands of both their climatic environment and their relationship with man. Completed in 2009, the first domesticated horse reference genome assembly (EquCab 2.0) produced most of the publicly available genetic variations annotations in this species. Yet, there are around 400 geographically and physiologically diverse breeds of horse. To enrich the current collection of genetic variants in the horse, we sequenced whole genomes from six horses of six different breeds: an American Miniature, a Percheron, an Arabian, a Mangalarga Marchador, a Native Mongolian Chakouyi, and a Tennessee Walking Horse, and mapped them to EquCab3.0 genome. Aside from extreme contrasts in body size, these breeds originate from diverse global locations and each possess unique adaptive physiology. A total of 1.3 billion reads were generated for the six horses with coverage between 15x to 24x per horse. After applying rigorous filtration, we identified and functionally annotated 17,514,723 Single Nucleotide Polymorphisms (SNPs), and 1,923,693 Insertions/Deletions (INDELs), as well as an average of 1,540 Copy Number Variations (CNVs) and 3,321 Structural Variations (SVs) per horse. Our results revealed putative functional variants including genes associated with size variation like LCORL gene (found in all horses), ZFAT in the Arabian, American Miniature and Percheron horses and ANKRD1 in the Native Mongolian Chakouyi horse. We detected a copy number variation in the Latherin gene that may be the result of evolutionary selection impacting thermoregulation by sweating, an important component of athleticism and heat tolerance. The newly discovered variants were formatted into user-friendly browser tracks and will provide a foundational database for future studies of the genetic underpinnings of diverse phenotypes within the horse.

Whole genome detection of sequence and structural polymorphism in six diverse horses.

. Conservation and breeding programmes of livestock species
depend on determination of genetic diversity. Today in livestock species,
microsatellite markers are commonly used to reveal population structure and
genetic diversity in both breeds and varieties. In this study, population
structure, genetic diversity, and differentiation among four native Turkish
sheep breeds including Guney Karaman, Kangal, Norduz, and Karakas were
assessed by using 21 microsatellite loci. By genotyping 120 individuals
belonging to four sheep breeds, a total of 275 different alleles, 37 of which
were private alleles, were observed across all loci. The mean number of
alleles per breed ranged from 7.28 (Guney Karaman) to 8.09 (Karakas), while
allelic richness ranged from 7.22 (Guney Karaman) to 7.87 (Karakas). Mean
observed heterozygosity varied from 0.60 (Kangal) to 0.66 (Norduz and
Karakas). The lowest pairwise FST value (0.084) was between Kangal and
Karakas populations, while the highest pairwise FST value (0.142) was
between Norduz and Karakas populations. Polymorphic information content (PIC)
values, ranging from 0.71 (ETH10) to 0.91 (OarFCB304), were highly
polymorphic (PIC  >  0.5) and informative in studied populations. In
the present study, the results of phylogenetic analysis were of importance,
since all studied populations have been accepted as Akkaraman varieties till
today. However, factorial correspondence and structure analysis, pairwise
 FST values, and an unweighted pair group method with arithmetic mean
analysis (UPGMA) dendrogram revealed that Guney Karaman and Norduz
populations have became genetically different from the Akkaraman breed due being
raised in different parts of Turkey under different climatic conditions
together with their breeding practices. Therefore, we recommend that more
comprehensive molecular studies should be conducted to clarify genetic
differentiation of Akkaraman sheep varieties.

/pdf/assessment-of-genetic-diversity-and-differentiation-among-2hyjzzkexd.pdf

Assessment of genetic diversity and differentiation among four indigenous Turkish sheep breeds using microsatellites

In contrast to high genetic diversity of mitochondrial DNA (mtDNA), equine Y chromosome shows extremely low variability, implying limited patrilines in the domesticated horse. In this study, we applied direct sequencing and restriction fragment length polymorphism (RFLP) methods to investigate the polymorphisms of 33 Y chromosome specific loci in 304 Chinese indigenous horses from 13 breeds. Consequently, two Y-single nucleotide polymorphisms (SNPs) (Y-45701/997 and Y-50869) and one Y-indel (Y- 45288) were identified. Of those, the Y-50869 (T>A) revealed the highest variation frequency (24.67%), whereas it was only 3.29% and 1.97% in Y-45288 (T/-) and Y-45701/997 (G>T) locus, respectively. These three mutations accounted for 27.96% of the total samples and identified five Y-SNP haplotypes, demonstrating genetic diversity of Y chromosome in Chinese horses. In addition, all the five Y- SNP haplotypes were shared by different breeds. Among 13 horse breeds analyzed, Balikun horse displayed the highest nucleotide diversity (π = 5.6×10 -4 ) and haplotype diversity (h = 0.527), while Ningqiang horse showed the lowest nucleotide diversity (π = 0.00000) and haplotype diversity (h = 0.000). The results also revealed that Chinese horses had a different polymorphic pattern of Y

/pdf/y-single-nucleotide-polymorphisms-diversity-in-chinese-3szu3yxoal.pdf

Y-Single Nucleotide Polymorphisms Diversity in Chinese Indigenous Horse.

The DMRT3 gene mutation in Chinese horse breeds.

Recent transcriptomic analysis of the bovine Y chromosome revealed abundant presence of multi-copy protein coding gene families on the male-specific region of the Y chromosome (MSY). Copy number variations (CNVs) of several MSY genes are closely related to semen quality and male reproduction in cattle. However, the CNVs of MSY genes in water buffalo are largely unknown. Therefore, this study aimed to investigate the CNVs of HSFY and ZNF280BY of 298 buffaloes from 17 populations distributed in China, Vietnam and Laos using quantitative PCR. Our results revealed that the median copy numbers of the HSFY and ZNF280BY genes were 47 (ranging from 20 to 145) and 269 (ranging from 73 to 974) respectively. In conclusion, this study indicated that HSFY and ZNF280BY showed abundant CNVs within swamp buffalo populations.

HSFY and ZNF280BY show copy number variations within 17 water buffalo populations.

The genetic diversity analysis in the donkey myostatin gene

Adipose triglyceride lipase (ATGL) is the key enzyme for the degradation of triacylglycerols (TAGs). It functions in concert with other enzymes to mobilize TAG and supply fatty acids (FAs) for energy production. Dysregulated lipolysis leads to excess concentrations of circulating FAs, which may lead to destructive and lipotoxic effects to the organism. To understand the role of ATGL in mammary lipid metabolism, ATGL was overexpressed in goat mammary epithelial cells (GMECs) by using a recombinant adenovirus system. ATGL overexpression decreased lipid droplet (LD) accumulation and cellular TG content (p< 0.05) along with a decrease in the expression of the key enzyme that catalyzes the final step of TG synthesis (DGAT). Significant increases were observed in the expression of genes related to lipolysis (hormone-sensitive lipase [HSL]) and FA desaturation (SCD) by ATGL overexpression. Genes responsible for FA oxidation (PPARα), LD formation and secretion (ADRP and BTN1A1), and long-chain FA uptake (CD36) were all decreased by ATGL overexpression (p < 0.05). The primary products of TAG lipolysis, free FAs (FFAs), were notably increased in the ATGL-overexpressing cells. Taken together, our results demonstrated that ATGL activation impairs lipid formation partially through accelerating lipolysis in GMECs.

Overexpression of ATGL impairs lipid droplet accumulation by accelerating lipolysis in goat mammary epithelial cells.

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