Biomedical Sciences - Unit 2

Lactose

Disaccharide sugar found in milk

Lactase

Breaks down lactose into two monosaccharides, glucose and galactose. These sugars are absorbed by cells in the small intestine and used as a source of energy.

Energy Conservation

1. Takes energy to produce any enzyme, including lactase, which is needed to digest milk

2. Typically, mammals don’t consume milk once they have stopped nursing

3. Without milk consumption, energy spent producing lactase would be energy wasted at the cellular level

Energetically favorable option - decrease in lactase production after weaning

Lactose Intolerance

Occurs when undigested lactose passes into the large intestine. Increased sugar concentration in the large intestine creates an osmotic gradient that draws water in the gut causing cramping and diarrhea. Bacteria in the large intestine digests the lactose as food, creating gaseous by-products like methane, carbon dioxide and hydrogen. Leading to gas build up and flatulence.

Lactase Persistence

Continued production of lactase after weaning in about 35% of people

Lactase Gene

55,000 base pairs in length and translated into protein, and lactase that is 1927 amino acids in length

Lactase Biosynthesis

1. Transcription

2. Translation

3. Post-Translational Modifications

4. Expression on the Cell Membrane

Transcription

In the nucleus, Lactase gene is transcribed into Lactase-mRNA by RNA polymerase

Transcription Factors

Attracts the molecular machinery necessary for transcription. They can also attract eachother, forming a large transcription complex

General Transcription Factors

Complex of proteins that bind to promoter sites on the DNA. Are responsible for initiating transcription by binding RNA Polymerase and associated factors, as well as to other regulatory transcription factors.

Regulatory Transcription Factors

Act as activators or repressors. Activators increase expression and repressors decrease expression of a gene.

Activators

Bind to enhancer sites (particular stretches of DNA) and influence the probability and frequency of transcription by attracting general transcription factors to the transcription complex.

Enhancers

Far from the start of the gene, allowing activators to cause large loops in the DNA. This causes large loops in the DNA, which brings many distant but important transcription factors together in one large transcription complex. Increases rate of transcription in gene.

Single Nucleotide Polymorphism (SNP)

Type of mutation that involves changing one letter in the genetic code. Affects how strongly a general transcription factor or activator will bind to that piece of DNA.

SNP in Lactase Persistence

In lactase persistence an enhancer site located 13190 base pairs upstream from the Lactase gene has a “C” replaced by a “T”. Increases how strongly and often the transcription factor Oct1 binds to this site.

Oct1

Activator that causes more general transcription factors to bind the lactase gene. It leads to more transcription of lactase-mRNA.

Normal Adults

1. After weaning, there is a decrease in transcription factor activity at the lactase gene

2. Leads to decreased transcription of the lactase gene

3. Results in lower levels of Lactase in the enterocytes, and the inability to digest lactose in milk

Mutant (Lactase Persistent)

1. A mutation at an enhancer site located 13190 base pairs upstream of the lactase gene increases binding of an activator called Oct1

2. Oct1 attracts more general transcription factors of the lactase gene throughout the individuals adult life

3. Prevents the decreased transcription of the lactase gene that normally happens

4. Results in steady levels of lactase in the enterocytes and a retained ability to digest lactose in milk throughout adulthood

Neolithic Revolution

A period of time, between 12,000 and 6,000 years ago, where humans transitioned from a hunter-gatherer lifestyle to a farming-herding lifestyle. Saw a burst in innovation because humans developed new ways to interact with their environment, such as tools for planting and reaping crops, mills for grinding grains and pottery for storage of food. Also conceptual innovations like the calendar, and concepts of property and monetary systems. Ancient Egyptian calendar divided into three seasons based on agricultural activities.

Pastoralism

Cultural practice of milking livestock (goats, sheep, cows, and camels). Innovation of Neolithic Revolution adopted in various cultures between 12,00 and 7,000 years ago.

Bicultural Coevolution Theory

Proposes that pastoralism and lactase persistence coevolved (arose around the same time and both changes were reinforced by each other).

Convergent Evolution

Independent evolution of similar features in separate lineages. Lactase persistence and pastoralism arose and spread through Europe and Africa independently.

Earliest Evidence of Pastoralism

Discovered in the Middle East: bones of young cattle, slaughtered before their first birthdays, which indicates that humans in the area had begun domesticating and milking cattle. About 10,500 years old

Migration

Earliest domesticated cattle in Greece and Balkan States (8,000 years old) closely related to the domesticated cattle from the Middle East that the wild cattle found in Europe. Indicates migrants from the Middle East brought their cattle with them. Middle Eastern cattle herders had more advanced food technology, so they easily out-competed the local hunter-gatherers they encountered in Central and Northern Europe.

LP in Africa

Evolved independently from the European lineage. Mutations responsible for lactase persistence are different. Neolithic humans in Africa experienced similar selective pressures to adopt pastoralism and evolve lactase persistence. People in Kenya and Sudan evolved lactase persistence through the same Oct1 transcription factor enhancer site, but through different mutations (G-13915 and G-13907)

How Lactase Persistence Spread

Through positive selection (for advantageous traits) and negative selection (against disadvantageous traits). It is a dominant trait meaning if one parent is homozygous for lactase persistent, all the children will be lactase persistent

Negative Selection

• Individually - Missed on a potentially important source of nutrition and hydration

• Experiencing painful, dehydrating symptoms upon consuming milk, which. could be deadly

• Culturally - Without pastoralism, herders must slaughter their livestock to gain dietary protein from their meat

Positive Selection

• Individually - Milk supplies protein, fat, sugar and vitamins and is dependable despite cold weather and/or bad crops

• Neolithic women who could digest milk were estimated to produce 32% more offspring

• Culturally - Milk is a more efficient protein source, doesn’t require killing livestock, yet the milk from one cow nearly equals the caloric value of the meat from a whole cow