Biology subjects

Gerlinger, E. R.

Publications and source records attributed to Gerlinger, E. R..

3 recordsLinked to original sources

bioRxiv2021

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 within 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 or Mageb5. Via sequence comparisons, we find mouse 4930567H17Rik and Mageb5 have human orthologs, 4930567H17Rik is rapidly diverging in rodents and primates, and 4930567H17Rik is harbored in a palindrome in humans and mice, while Mageb5 is not. 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. Summary sentenceMice lacking X-palindromic gene families display normal male fertility, fecundity, spermatogenesis, and gene expression but exhibit differences in sperm head morphology, suggesting a potential role for these gene families in sperm development.

genetics↗

bioRxiv2019

Large X-linked palindromes undergo arm-to-arm gene conversion across Mus lineages

Large (>10kb), nearly-identical (>99% nucleotide identity), palindromic sequences are enriched on mammalian sex chromosomes. Primate Y-palindromes undergo high rates of arm-to-arm gene conversion, a proposed mechanism for maintaining their sequence integrity in the absence of X-Y recombination. It is unclear whether X-palindromes, which can freely recombine in females, undergo arm-to-arm gene conversion and, if so, at what rate. We generated high-quality sequence assemblies of Mus molossinus and Mus spretus X-palindromic regions and compared them to orthologous Mus musculus X-palindromes. Our evolutionary sequence comparisons found evidence of X-palindrome arm-to-arm gene conversion at rates comparable to rates of autosomal allelic gene conversion in mice. Mus X-palindrome genes also exhibit higher than expected sequence diversification, indicating gene conversion may facilitate the rapid evolution of palindrome-associated genes. We conclude that in addition to maintaining genes sequence integrity via sequence homogenization, arm-to-arm gene conversion can also rapidly drive genetic evolution via sequence diversification.

genetics↗

bioRxiv2018

Male mice with large inversions or deletions of X-palindrome arms are fertile and express their associated genes post-meiosis.

Large (>10 kb) palindromic sequences are enriched on mammalian sex chromosomes. In mice, these palindromes harbor gene families ([≥]2 gene copies) expressed exclusively in post-meiotic testicular germ cells, at a time when most single-copy sex-linked genes are transcriptionally repressed. This distinct expression pattern led to the hypothesis that containment within palindrome structures or having [≥]2 gene enables post-meiotic gene expression. We tested these two hypotheses by using CRISPR to precisely engineer large (10s of kb) inversions and deletions of X chromosome palindrome arms for two regions carrying the mouse 4930567H17Rik and Mageb5 gene families. We found that 4930567H17Rik and Mageb5 gene expression is unaffected in mice carrying palindrome arm inversions, suggesting that palindromic structure is not important for mediating palindrome-associated gene expression. We also found that 4930567H17Rik and Mageb5 gene expression is reduced by half in mice carrying palindrome arm deletions, allowing us to test whether palindrome-associated genes are sensitive to reduced expression levels resulting in spermatogenic defects. Male mice carrying palindrome arm deletions of 4930567H17Rik or Mageb5, however, are fertile, have normal testis histology, and show no aberrations in spermatogenic cell population frequencies via FACS quantification. Together, these findings suggest that large palindromic structures on the sex chromosomes are not necessary for their associated genes to evade post-meiotic transcriptional repression and that these genes are not sensitive to reduced expression levels. Large sex chromosome palindromes may thus be important for other reasons, such as the long-term evolutionary stability of their associated gene families.

genetics↗