Comparative Genomics Analysis of Cation Channel Sperm-associated
Proteins (CATSPERs) Associated with Sperm Motility in Livestock
Kun Li1,2, Mubbashar Hassan3, Hafiz Ishfaq
Ahmad4*, Abid Hussain Shahzad3, Sanan Raza3,
Iram Qadeer5, Sayyed Aun Muhammad6, and
Wentong Liu7*
1College
of Veterinary Medicine, Nanjing Agricultural University, Nanjing
210095, China; 2School of Basic Medicine, Hubei
University of Arts and Science, 296 Longzhong Road, Xiangyang,
441053, China; 3Department of Clinical Sciences,
Theriogenology Section, College of Veterinary and Animal Sciences,
Jhang, Sub Campus UVAS, Lahore, Pakistan; 4Department of
Animal Breeding and Genetics, Faculty of Veterinary and Animal
Sciences, The Islamia University of Bahawalpur, Pakistan; 5Department
of Zoology, The Govt. Sadiq College Women University, Bahawalpur,
Pakistan; 6Department of Clinical Sciences, College of
Veterinary and Animal Sciences, Jhang, Sub Campus UVAS, Lahore,
Pakistan; 7School of Basic Medicine, Hubei University of
Arts and Science, 296 Longzhong Road, Xiangyang, 441053, China.
The CATSPER gene family encodes essential ion channels that govern sperm
motility and male fertility across mammalian species. This study presents a
comprehensive evolutionary and functional analysis of CATSPER genes (CATSPER
1-4) in cattle, sheep and pigs, integrating comparative genomics, analysis of
selection pressure, and structural characterization. Using maximum likelihood
models (M1a/M2a and M7/M8), strong signatures of positive selection in all four
CATSPER genes were identified (2Δℓ=38.27-67.45, P<0.05), with Bayesian Empirical
Bayes analysis revealing 11-17 positively selected sites per gene. These
adaptive mutations were predominantly located in ion transport domains (Pfam)
and showed lineage-specific patterns, particularly in primate CATSPER2/4.
Concurrently, purifying selection maintained critical functional regions, as
evidenced by high conservation scores (ConSurf) and structural integrity
(ERRAT>74.32). Phylogenetic reconstruction demonstrated deep conservation of
CATSPER proteins across Artiodactyla, with gene duplication events observed in
rodent lineages. Functional characterization revealed 4-6 transmembrane domains
per protein and identified key post-translational modification sites (phosphorylation,
glycosylation). Protein-protein interaction networks (STRING) implicated CATSPER
in a reproductive complex with AKAP3, SPAG6/16, and CABYR, regulating flagellar
calcium signaling. Notably, nuclear hormone receptor binding motifs were
predicted in promoter regions, suggesting endocrine regulation of CATSPER
expression. These findings provide evolutionary and mechanistic insights into
CATSPER-mediated fertility, highlighting the followings: 1) Adaptive evolution
in ion transport domains correlates with species-specific sperm motility
requirements, 2) Structural conservation maintains core channel function despite
lineage-specific adaptations, and 3) Protein interaction networks integrate
CATSPER into broader sperm motility pathways. The study establishes a framework
for targeting CATSPER variants in livestock breeding programs and informs
comparative models of male fertility across mammals.
To Cite This Article:
Kun L, Hassan M, Ahmad HI, Shahzad AH, Raza S, Qadeer I, Muhammad SA and Liu W
2025. Comparative genomics analysis of
cation channel sperm-associated proteins (CATSPERs) associated with sperm
motility in livestock. Pak Vet J.
http://dx.doi.org/10.29261/pakvetj/2025.240