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Human testis-specific genes are under relaxed negative selection

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Abstract

Recent studies have suggested that selective forces and constraints acting on genes varied during human evolution depending on the organ in which they are expressed. To gain insight into the evolution of organ determined negative selection forces, we compared the non-synonymous SNP diversity of genes expressed in different organs. Based on a HAPMAP dataset, we determined for each SNP its frequency in 11 human populations and, in each case, predicted whether or not the change it produces is deleterious. We have shown that, for all organs under study, SNPs predicted to be deleterious are present at a significantly lower frequency than SNPs predicted to be tolerated. However, testis-specific genes contain a higher proportion of deleterious SNPs than other organs. This study shows that negative selection is acting on the whole human genome, but that the action of negative selection is relaxed on testis-specific genes. This result adds to and expands the hypothesis of a recent evolutionary change in the human male reproductive system and its behavior.

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Acknowledgments

This research was supported by the National Science Foundation (grants BCS-0550209 and BCS-0827546), the Region Aquitaine (projet MAGE), the Agence Nationale de la Recherche (ANR-12-PDOC-0037-01) and the Association contre les maladies mitochondriales.

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Authors and Affiliations

  1. Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, 48201, USA

    Denis Pierron & Lawrence I. Grossman

  2. Laboratoire de Physiopathologie Mitochondriale, INSERM, Université Victor Segalen Bordeaux, 2, 146, rue Léo Saignat, 33076, Bordeaux, France

    Denis Pierron, Harilanto Razafindrazaka, Christophe Rocher & Thierry Letellier

  3. Laboratoire AMIS-UMR 5288, CNRS, Université de Toulouse, 37 Allées Jules Guesde, 31073, Toulouse, France

    Denis Pierron, Harilanto Razafindrazaka & Thierry Letellier

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  1. Denis Pierron
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  2. Harilanto Razafindrazaka
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  3. Christophe Rocher
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  4. Thierry Letellier
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  5. Lawrence I. Grossman
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Correspondence to Lawrence I. Grossman.

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Communicated by S. Hohmann.

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Supplementary information.

Supplementary Table 1 Numbers of SNPs located on tissue specific genes according their prediction status based on dbSNP, POLYPHEN, and SIFT and according to their tissue specificity.

Supplementary Table 2 iHS p value estimated by Haplotter for testis-specific expressed genes presenting a deleterious or damaging SNP and reaching a maximal frequency of at least 15 %.

Supplementary Table 3 iHS values estimated by Whamm! for SNPs located on testis-specific expressed genes presenting a deleterious or damaging prediction and for each population where it reaches a frequency of at least 15 %.

Supplementary Table 4: F ST values estimated by SPSmart for SNPs located on testis-specific expressed genes presenting a deleterious or damaging prediction and reaching a maximal frequency of at least 15 %.

Supplementary Table 5 Numbers of genes presenting a predicted deleterious SNP and presenting paralogous genes in human genomes or orthologous genes in mouse and zebrafish genomes.

Supplementary Figure S1 Proportion of SNPs located on testis-specific genes compared to other SNPs according their effect prediction (dbSNP, SIFT, and POLYPHEN) and their frequency (rare <5 %, common ≥5 %).

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Pierron, D., Razafindrazaka, H., Rocher, C. et al. Human testis-specific genes are under relaxed negative selection. Mol Genet Genomics 289, 37–45 (2014). https://doi.org/10.1007/s00438-013-0787-z

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  • DOI: https://doi.org/10.1007/s00438-013-0787-z

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