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SSADH Variation in Primates: Intra- and Interspecific Data on a Gene with a Potential Role in Human Cognitive Functions

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Abstract

In the present study we focus on the nucleotide and the inferred amino acid variation occurring in humans and other primate species for mitochondrial NAD+-dependent succinic semialdehyde dehydrogenase, a gene recently supposed to contribute to cognitive performance in humans. We determined 2527 bp of coding, intronic, and flanking sequences from chimpanzee, bonobo, gorilla, orangutan, gibbon, and macaque. We also resequenced the entire coding sequence on 39 independent chromosomes from Italian families. Four variable coding sites were genotyped in additional populations from Europe, Africa, and Asia. A test for constancy of the nonsynonymous vs. synonymous rates of nucleotide changes revealed that primates are characterized by largely variable d N /d S ratios. On a background of strong conservation, probably controlled by selective constraints, the lineage leading to humans showed a ratio increased to 0.42. Human polymorphic levels fall in the range reported for other genes, with a pattern of frequency and haplotype structure strongly suggestive of nonneutrality. The comparison with the primate sequences allowed inferring the ancestral state at all variable positions, suggesting that the c.538(C) allele and the associated functional variant is indeed a derived state that is proceeding to fixation. The unexpected pattern of human polymorphism compared to interspecific findings outlines the possibility of a recent positive selection on some variants relevant to new cognitive capabilities unique to humans.

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Acknowledgments

We gratefully acknowledge Dr. A. Di Rienzo and two anonymous reviewers for their helpful comments on the first draft of this work. We thank Dr. M. Basile for computational support. This work was supported by grants MIUR 60% to Prof. Carla Jodice, PRIN 2003 and 60% to A.N., and CEGBA (Centro di Eccellenza Geni in campo Biosanitario e Agroalimentare) and European Commission (INPRIMAT, QLRI-CT-2002-01325) to M.R.

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Authors and Affiliations

  1. Department of Biology, University “Tor Vergata”, via della Ricerca Scientifica, snc, 00133, Rome, Italy

    Paola Blasi, Francesca Palmerio, Patrizia Malaspina & Andrea Novelletto

  2. Department of Cell Biology, University of Calabria, Rende, Italy

    Aurora Aiello & Andrea Novelletto

  3. DAPEG, Section of Genetics, University of Bari, Bari, Italy

    Mariano Rocchi

Authors
  1. Paola Blasi
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  2. Francesca Palmerio
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  3. Aurora Aiello
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  4. Mariano Rocchi
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  5. Patrizia Malaspina
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  6. Andrea Novelletto
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Correspondence to Andrea Novelletto.

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[Reviewing Editor: Dr. Martin Kreitman]

Paola Blasi and Francesca Palmerio contributed equally to the work.

Appendix

Appendix

Alignment of sequences obtained in the present paper (see Materials and Methods) to human AL031230 is shown in Fig. A1. Noncoding and coding sequences are in lowercase and uppercase, respectively. Numbering refers to AL031230. Boundaries between noncontiguous genomic sequences concatenated here are shown. The arrow marks the first nucleotide of the mature peptide.

Figure A1
figure 3figure 3figure 3figure 3figure 3

Alignment of sequences obtained in the present paper (see Materials and Methods) to human AL031230. Non coding and coding sequences are in lower and upper case, respectively. Numbering refers to AL031230. Boundaries between non-contiguous genomic sequences here concatenated are shown. The arrow marks the first nucleotide of the mature peptide.

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Blasi, P., Palmerio, F., Aiello, A. et al. SSADH Variation in Primates: Intra- and Interspecific Data on a Gene with a Potential Role in Human Cognitive Functions. J Mol Evol 63, 54–68 (2006). https://doi.org/10.1007/s00239-005-0154-8

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  • DOI: https://doi.org/10.1007/s00239-005-0154-8

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