Human Genetics

, Volume 117, Issue 4, pp 329–339 | Cite as

Microsatellite variation and evolution of human lactase persistence

  • Margarida Coelho
  • Donata Luiselli
  • Giorgio Bertorelle
  • Ana Isabel Lopes
  • Susana Seixas
  • Giovanni Destro-Bisol
  • Jorge RochaEmail author
Original Investigation


The levels of haplotype diversity within the lineages defined by two single-nucleotide polymorphisms (SNPs) (−13910 C/T and −22018 G/A) associated with human lactase persistence were assessed with four fast-evolving microsatellite loci in 794 chromosomes from Portugal, Italy, Fulbe from Cameroon, São Tomé and Mozambique. Age estimates based on the intraallelic microsatellite variation indicate that the −13910*T allele, which is more tightly associated with lactase persistence, originated in Eurasia before the Neolithic and after the emergence of modern humans outside Africa. We detected significant departures from neutrality for the −13910*T variant in geographically and evolutionary distant populations from southern Europe (Portuguese and Italians) and Africa (Fulbe) by using a neutrality test based on the congruence between the frequency of the allele and the levels of intraallelic variability measured by the number of mutations in adjacent microsatellites. This result supports the role of selection in the evolution of lactase persistence, ruling out possible confounding effects from recombination suppression and population history. Reevaluation of the available evidence on variation of the −13910 and −22018 loci indicates that lactase persistence probably originated from different mutations in Europe and most of Africa, even if 13910*T is not the causal allele, suggesting that selective pressure could have promoted the convergent evolution of the trait. Our study shows that a limited number of microsatellite loci may provide sufficient resolution to reconstruct key aspects of the evolutionary history of lactase persistence, providing an alternative to approaches based on large numbers of SNPs.


Microsatellite Locus Lactase Demographic Model Lactase Persistence Recombination Suppression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank Luís Pedro Resende and Cinzia Battaggia for assistance in typing the Portuguese and Italian samples, respectively. We are also grateful to Gabriella Spedini for the Fulbe DNA samples and to António Prista and Sílvio Saranga for the Mozambique samples. We thank Eduardo Tarazona-Santos and Nuno Ferrand for comments on the manuscript. This research was supported by the Sociedade Portuguesa de Gastrenterologia and by the Fundação para a Ciência e a Tecnologia (grants POCTI/42510/ANT/2001 and POCTI/BIA-BDE/56654/2004). D.L. and G.D.B. were supported by the M.I.U.R. (grant numbers 2003054059 and 2005058414).

Supplementary material

Table S1 Distribution of phased haplotypes consisting of the -13.910 kb C/T and -22.018 kb G/A SNPs and microsatellites D2S3010, D2S3013, D2S3015 and D2S3016

439_2005_1322_ESM_table1.pdf (192 kb)
(PDF 192 KB)

Fig. S1 Microsatellite allele frequency distributions within C-G and T-A haplotypes defined by –13.910kb/-22.018kb SNPs in different populations

439_2005_1322_ESM_fig1.pdf (63 kb)
(PDF 63 KB)


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Margarida Coelho
    • 1
    • 2
  • Donata Luiselli
    • 3
  • Giorgio Bertorelle
    • 4
  • Ana Isabel Lopes
    • 5
  • Susana Seixas
    • 1
  • Giovanni Destro-Bisol
    • 6
    • 7
  • Jorge Rocha
    • 1
    • 2
    Email author
  1. 1.Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP)PortoPortugal
  2. 2.Departamento de Zoologia Antropologia, Faculdade de CiênciasUniversidade do PortoPortoPortugal
  3. 3.Dipartimento di Biologia Evoluzionistica SperimentaleUniversita di BolognaBolognaItalia
  4. 4.Sezione di Biologia Evolutiva, Dipartimento di BiologiaUniversitá di FerraraFerraraItalia
  5. 5.Unidade de Gastrenterologia Pediátrica, Hospital de Santa MariaLisbonPortugal
  6. 6.Dipartimento di Biologia Animale e dell’ UomoUniversitá “La Sapienza”RomeItaly
  7. 7.Istituto Italiano di AntropologiaRomeItaly

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