X-linked palindromic gene families 4930567H17Rik and Mageb5 are dispensable for male mouse fertility.

Mammalian sex chromosomes are enriched for large, nearly-identical, palindromic sequences harboring genes expressed predominately in testicular germ cells. Discerning if individual palindrome-associated gene families are essential for male reproduction is difficult due to challenges in disrupting all copies of a gene family. Here we generate precise, independent, deletions to assess the reproductive roles of two X-linked palindromic gene families with spermatid-predominant expression, 4930567H17Rik and Mageb5. Sequence analyses reveals mouse 4930567H17Rik and Mageb5 are orthologs of human HSFX3 and MAGEB5, respectively, where 4930567H17Rik/HSFX3 is harbored in a palindrome in humans and mice, while Mageb5 is not. Additional sequence analyses show 4930567H17Rik and HSFX3 are rapidly diverging in rodents and primates, respectively. Mice lacking either 4930567H17Rik or Mageb5 gene families do not have detectable defects in male fertility, fecundity, spermatogenesis, or in gene regulation, but do show differences in sperm head morphology, suggesting a potential role in sperm function. We conclude that while all palindrome-associated gene families are not essential for male fertility, large palindromes influence the evolution of their associated gene families.