title: Effects of different kinds of essentiality on sequence evolution of human testis proteins.
abstract: We asked if essentiality for either fertility or viability differentially affects sequence evolution of human testis proteins. Based on murine knockout data, we classified a set of 965 proteins expressed in human seminiferous tubules into three categories: proteins essential for prepubertal survival ("lethality proteins"), associated with male sub- or infertility ("male sub-/infertility proteins"), and nonessential proteins. In our testis protein dataset, lethality genes evolved significantly slower than nonessential and male sub-/infertility genes, which is in line with other authors' findings. Using tissue specificity, connectivity in the protein-protein interaction (PPI) network, and multifunctionality as proxies for evolutionary constraints, we found that of the three categories, proteins linked to male sub- or infertility are least constrained. Lethality proteins, on the other hand, are characterized by broad expression, many PPI partners, and high multifunctionality, all of which points to strong evolutionary constraints. We conclude that compared with lethality proteins, those linked to male sub- or infertility are nonetheless indispensable, but evolve under more relaxed constraints. Finally, adaptive evolution in response to postmating sexual selection could further accelerate evolutionary rates of male sub- or infertility proteins expressed in human testis. These findings may become useful for in silico detection of human sub-/infertility genes.
authors.affiliation: Institute of Anthropology, Johannes Gutenberg University Mainz, Anselm-Franz-von-Bentzel-Weg 7, D-55099, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Schumacher
authors.affiliation: Institute of Anthropology, Johannes Gutenberg University Mainz, Anselm-Franz-von-Bentzel-Weg 7, D-55099, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Zischler
authors.affiliation: Institute of Anthropology, Johannes Gutenberg University Mainz, Anselm-Franz-von-Bentzel-Weg 7, D-55099, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Herlyn
mesh_terms: D000818:Animals; D019295:Computational Biology / Q000379:methods; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D058977:Molecular Sequence Annotation; D009928:Organ Specificity / Q000235:genetics; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012671:Seminiferous Tubules / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics; D013737:Testis / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D011506:Proteins