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I Ciara Fitzpatrick, 16414016, have read and fully understand the UCD Library Guidelines on Plagiarism, the Official UCD Policy on Plagiarism and the UCD Briefing for Students on Academic Integrity and Plagiarism.

Gene-culture coevolution between cattle milk protein genes and human lactase genes
Ciara Fitzpatrick 16414016
Does gene-culture coevolution exist between cattle and humans? Can gene-culture coevolution between humans and a domestic species positively impact our genome? And what actually is gene-culture coevolution? Six of the most important milk coding genes from approximately 20,000 domestic cattle across 70 native European cattle breeds in various regions of Europe may help answer these questions. This paper explores the proposed reasons why some humans carry the lactase persistence allele in conjunction with the evolutionary changes and variation in the gene pool of cattle while considering the geographical locations of the findings.

Gene-culture coevolution is simply the gradual development of genetics and culture in synchronization. Social changes can impact natural selection processes (Laland, 2003). This proves true when evaluating the locations of Neolithic cattle farms dating back 5,000 years, which supplied milk to the surrounding populations and the areas that have the strongest presence of the lactase persistence gene today. It also coincides with the great variance of the six evaluated cattle milk proteins in these areas.
Cows milk is a staple component of many of our diets because of its beneficial nutritive qualities and it has been for over 8,000 years. However, not all humans possess the ability to break down lactose. The lactose persistence allele in adults is necessary for the milk lactose digesting process to take place. Lactose-tolerant people carry this variant form of the gene whereas lactose-intolerant people do not. Thereby, selection-based evolutionary change has taken place as humans naturally and genetically adapted to digesting milk where milk became readily available.

This study focused on nonsynonymous mutations within the specified six genes. These mutations usually involve an insertion or deletion of a single nucleotide in a sequence which in turn effects the protein it encodes (Xia and Li, 1998). This can have positive consequences for effected populations if the mutated gene is favourable for the functioning of the organism. Natural selection can drive evolution when the gene pool expands and diversifies.

Figure 1 The association between the locations of Neolithic cattle farms, high diversity in cattle milk protein genes and lactose-tolerant people of today occurring in North Central Europe.

Allelic richness is the alleles competency to survive a long adaptive future (Greenbaum et al., 2014). This, coupled with various unique genes, increases the diversity of native breeds in North Central Europe (NCE). This can be seen on the map (Fig. 1b) highlighted by the darkest orange/red region. The dispersal of cattle sampled is also visible on the map, distinguished by blue dots (Fig. 1a) and the location of Neolithic farms is represented by the dashed line (Fig 1c) encompassing the highly genetic diverse region. Do you see any trends?
In addition, the map illustrates the frequency of human lactase persistence alleles, the highest are shaded in the darkest orange and as the colours fade, the prevalence of the alleles decrease (Fig 1c). As we move further away from the Neolithic farming region (Fig 1c), humans are less capable of digesting lactose. It seems like the region within the dashed line (Fig 1c) provides vital information to this study.

It is no coincidence that Neolithic cattle farming sites, high allelic diversity in cattle and lactose tolerant people are all linked in the past or present to the NCE region. This is accomplished by gene-culture coevolution and the natural benefits of consuming milk.
Another aspect that proves this coevolution is the selection of loci that improve the protein component in which cattle themselves can and do synthesize a more nourishing milk. This is evident in the relationship between k-casein, an important milk protein gene and its higher presence in breeds in NCE. An investigation into Neolithic cattle intratooth shifts in levels of nitrogen isotope ratios suggests that these farmers weaned calves early in order to reap the rewards of cows milk. It appears that the people at this time were heavily reliant on milk.

Selection and its rapid evolutionary effects have a very significant bearing on the accumulated data. An expected rise in gene diversity in NCE cattle today did not take place. These population surveys of mtDNA sequences included the use of microsatellite and protein polymorphisms. This recent lack of increase in gene diversity is probably due to the intense selection pressure that was established in Neolithic times and that has rooted extensive allelic diversity in the six genes analysed. New mutations are visible, but they are not yet frequent enough to alter gene diversity on a macro scale. Over time these mutations may be selected for, if they contribute a valuable purpose, avoiding attrition from genetic drift and the disappearance of genes. It is unclear where the distinct genetic diversity of domestic cattle in NCE came from originally. The now extinct local wild aurochs and non-NCE domestic cattle seem the most obvious descendants but on closer evaluation are a highly unlikely match.

This experiment can be replicated quite easily but it would be a time-consuming undertaking because of the vastness in area, breed types and numbers of animals to be studied. No previous experiment can compare to this extraordinary compilation of data. Previous studies do not entirely correspond with the evidence that is displayed here but these inconsistencies are most likely due to the differences in criteria being assessed. For example, this study only focuses on nonsynonymous polymorphisms in the six milk protein genes.
The importance of this research cannot be understated from a scientific, social and socio-economic perspective. It gives us an understanding into cattle and evolutionary genomics. It shows how diverse these significant milk genes are and suggests that these NCE cattle genes could become highly efficient in future agricultural productivity.
Discoveries of negative gene-culture coevolution between humans and parasites have been recorded but this is the first study to prove the positives impacts. In essence, “the cow, the wild creature, had not only been domesticated, but had also entered the spiritual world of man” (Connell, 2018).
Bibliography
Connell, J. (2018). The Cow Book. London: Granta Books, p.42.

 Greenbaum, G., Templeton, A., Zarmi, Y. and Bar-David, S. (2014). Allelic Richness following Population Founding Events – A Stochastic Modeling Framework Incorporating Gene Flow and Genetic Drift. PLoS ONE, 9(12), p.e115203.

Laland, K. (2003). Gene-Culture Coevolution. In: Encyclopedia of Cognitive Science. London: Nature publishing group.

Xia, X. and Li, W. (1998). What Amino Acid Properties Affect Protein Evolution?. Journal of Molecular Evolution, 47(5), pp.557-564.

This paper that I have summarised was Albano Beja-Pereira, Gordon Luikart, Philip R England, Daniel G Bradley, Oliver C Jann, Giorgio Bertorelle, Andrew T Chamberlain, Telmo P Nunes, Stoitcho Metodiev, Nuno Ferrand and Georg Erhardt. Published in Nature Genetics, Volume 35, Number 4 in December 2003 by Nature Publishing Group.

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