Question

Topic: Lactase persistence, enzymes, and genetic expression We started this term looking at the persistence of the enzyme lactase, which breaks down a specific sugar in milk. Lactase persistence shows interesting global distribution patterns due to evolution and natural selection. The lactase enzyme acts like many other biological catalysts. Write an essay about lactase persistence and the function and expression of the lactase enzyme. Make sure to address: Define evolution and the selection pressure that lead to diversity in lactase persistence. Include the necessary components for selection pressures to act. Give potential examples of each component for the lactase persistence system. Describe global patterns of lactase persistence. How lactase acts an enzyme. Include the substrate(s) and product(s), and in general how enzymes act as biological catalysts (make sure to define this). Describe the genetics of lactase persistence. Include dominant/recessive labels for lactase persistence/nonpersistence. • Briefly describe how the lactase enzyme is regulated and expressed (through protein synthesis).

Answer 1

Lactase persistance is a result of genetic mutation 3000 years ago in population where diary foods became an important diet component in adults and selective advantage has been seen in these gene mutations. When a natural selection favors a beneficial allele such as a lactase persistance allele the allele passes down from 1 generation to next and increases in its frequency. Some of the neutral markers which does not have a selective advantage but are carried along with the beneficial allele and their frequency also increases. As time passes by the association between beneficial allele and neutral markers breaks down due to recombination. Lactase is an enzyme responsible for the hydrolysis of glucose and galactose. After weaning period lactase usually declines in mammals and some are able to express lactase throughout adultlife which can then digest the lactase found in milk. This is called LP. They are seen in 35% of adults in the world today and high frequencies are seen in northern european populations. It varies from over 54% in eastern and southern europe and 86% in central and western europe. LP frequency in india is higher in northern states as with 63% and south has a 23%. In vitro studies indicates that single nucleotide polymorphisms affects lactase promoter activity and is likely to cause LP. LP associated alleles are found on different haplotypic backgrounds and hence LP has evolved multiple times and is an example of convergent evolution. LP coevolved with cultural adaptation of diarying as a gene culture evolution process.

Strong selective pressures might have been episodic and occurred under certain circumstances such as a drought or famine. For example during crop failure, milk was an alternative food and LP would have an advantage. In regions were water was scarce, milk was used by pastoralist groups and lactase non persistant individuals were at risk from conditions such as diarrhoea and selection might have been strong in lactase persistance individuals.

In case on an enzymatic work, the substrate lactose is broken down to glucose and galactose. When enzyme lactase binds to lactose its active site cleaves lactose to glucose and galactose and then are absorbed by the intestinal epithelial cells and are transported to blood. Hence it speeds up chemical reaction and remains same after reaction and are biological catalysts.

LP is a dominantly inherited genetic trait and distribution of lactose phenotypes in population are highly variable and is controlled by polymorphic cis  acting lactase gene. This single nucleotide polymorphism is seen 14kb upstream from transcription in an intron of the near gene called MCM6. Dominant allele is denoted by PP and recessive allele by pp. Lactase persistant phenotype involves high mRNA expression and high lactase activity and can digest lactose while lactase non persistant phenotype hhas low mRNA activity and low lactase. Enzyme lactase is encoded by LCT. Lactase is encoded by single gene on chromosome 2 and expressed exclusively on small intestine enterocytes and in low levels in colon during fetal development. ts down regulated after weaning results in little expression in small intestine which causes lactose intolerance.

Mutations C to T at position 13910 and G to A at position 22018 and independently linked to lactase persistance. Developmentally regulated DNA binding proteins downregulates the transcription and destabilize the mRNA transcripts causes decreased LPH expression after weaning.