Lactose digestion and the evolutionary genetics of lactase persistence

  title={Lactose digestion and the evolutionary genetics of lactase persistence},
  author={Catherine J. E. Ingram and Charlotte A. Mulcare and Yuval Itan and Mark George Thomas and Dallas M. Swallow},
  journal={Human Genetics},
It has been known for some 40 years that lactase production persists into adult life in some people but not in others. However, the mechanism and evolutionary significance of this variation have proved more elusive, and continue to excite the interest of investigators from different disciplines. This genetically determined trait differs in frequency worldwide and is due to cis-acting polymorphism of regulation of lactase gene expression. A single nucleotide polymorphism located 13.9 kb upstream… 

Evolutionary and molecular genetics of regulatory alleles responsible for lactase persistence

The results show that different mechanisms lead to a disruption of the normal down-regulation of lactase in adult life, and the finding of an extended region of high linkage disequilibrium in all populations, and an extended B haplotype is discussed in relation to the methods to study selection.

The Onset of Lactase Persistence in Europe

Various studies, from archaeology to population genetics, that have shed some light on the evolution of LP in Europe are discussed, suggesting that LP arose after dairying practices had developed.

Population Genetics of Lactase Persistence and Lactose Intolerance

The phenotypic polymorphism and the evidence that the genetic trait involves regulation of expression of the lactase gene and is caused by multiple independent mutations that have reached high frequencies in different populations, because of the benefits of drinking milk are described.

Genetic origins of lactase persistence and the spread of pastoralism in Africa.

Genetic diversity of lactase persistence in East African populations

It is shown that with the exception of Copts and Nilotic populations who are fully lactose non-persistent, the majority of populations of East Africa show at least partly lactose persistence, with both ethnic and socio-economic aspects playing an important role in the distribution of genetic variants.

Diversity of lactase persistence alleles in Ethiopia: signature of a soft selective sweep.

Why and when was lactase persistence selected for? Insights from Central Asian herders and ancient DNA

It is proposed that Central Asian herders have adapted to milk consumption culturally, by fermentation, and/or by colonic adaptation, rather than genetically, which coincides well with the migration of steppe populations across and outside of Europe.

Evolution of lactase persistence: an example of human niche construction

How genetic and archaeological information can be integrated to bring new insights to the origins and spread of lactase persistence is illustrated by three simulation studies that have shed light on the evolution of this trait in Europe.

Frequency of lactase persistence genotype in a healthy Polish population

Allele frequencies obtained are in agreement with results from other countries and confirm the unique pattern of distribution of the LCT-13910C>T genotype in Europe.



The evolutionary genetics of lactase persistence in Africa and the Middle East

The occurrence of only one -13910*T carrier out of 45 lactase persistent people from a cohort of phenotyped Sudanese individuals provided confirmation that the allele is not causal worldwide, and the cluster of lactase persistence associated alleles within a single regulatory element implies that they are causal.

The lactase persistence/non-persistence polymorphism is controlled by a cis-acting element.

This work exploited known DNA 'marker' polymorphisms within the exons of the lactase gene to examine the expression of the individual lactase mRNA transcripts from persistent and non-persistent individuals in order to determine whether the regulation is in cis or trans.

A novel polymorphism associated with lactose tolerance in Africa: multiple causes for lactase persistence?

A cohort study of lactose digester and non-digester Sudanese volunteers shows there is no association of -13910*T or the A haplotype with lactase persistence, and reveals the complexity of this phenotypic polymorphism and highlights the limitations of C-13910T as a diagnostic test for lact enzyme persistence status, at least for people with non-European ancestry.

The evolution of the lactase persistence phenotype

Variation in and around the lactase gene is examined to explore the possible role of natural selection in explaining modern frequencies of lactase persistence and a series of single nucleotide polymorphisms in the vicinity of the lact enzyme gene have alleles known to associate with lactases persistence in Northern Europe.

Lactase haplotype diversity in the Old World.

It is suggested that genetic drift was important in shaping the general pattern of non-African haplotype diversity, with recent directional selection in northern Europeans for the haplotype associated with lactase persistence.

Absence of the lactase-persistence-associated allele in early Neolithic Europeans

A stepwise strategy for obtaining reliable nuclear ancient DNA from ancient skeletons is developed, which obtained high-confidence LP-associated genotypes from eight Neolithic and one Mesolithic human remains, using a range of strict criteria for ancient DNA work.

Evidence of still-ongoing convergence evolution of the lactase persistence T-13910 alleles in humans.

The data about global allelic haplotypes of the lactose-tolerance variant imply that the T(-13910) allele has been independently introduced more than once and that there is a still-ongoing process of convergent evolution of the LP alleles in humans.

Microsatellite variation and evolution of human lactase persistence

This 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.

DNA Polymorphisms in the Lactase Gene

Simple polymerase chain reaction-based procedures were used, combined with silver staining as a method of detection, and a region of linkage disequilibrium was observed which spans the whole coding region of the lactase gene (∼ 60–70 kb).

Lactase haplotype frequencies in Caucasians: association with the lactase persistence/non-persistence polymorphism.

It appears that lactase persistence arose more recently than the DNA marker polymorphisms used here to define the main Caucasian haplotypes, possibly as a single mutation on the A haplotype background.