molecular biology lecture two

intro to Darwin
1.  theory
2.  evidence
3.  thinking about

4.  scientific method
5.  Alternatives to Darwin
6.  Molecular Biology
7.  The Origin of Life

problems for Darwin
8. punctuation
9. convergence
10. complexity
11. humans
12. multiregional

13. genome topology: intro
14. ontogeny 1
15. ontogeny 2
16. comparative genomics
17. GT: applications

engineering human evolution
18. eugenics
19. enhancement
20. epenes

molecular biology, lecture two

protein synthesis

In a gene, each sequence of three base pairs causes one of twenty different amino acids to be produced. The amino acids are produced in sequence and are joined together to form that gene’s protein. Amino acids are the building blocks from which proteins are constructed.

The step in protein synthesis which involves the gene is called transcription. A protein, RNA polymerase, produces a RNA strand from the DNA sequence of a gene.

That RNA sequence, called messenger RNA or mRNA then moves outside the nucleus to a structure in the cell cytoplasm called a ribosome where mRNA is translated into a sequence of amino acids. These amino acids are assembled, one after another, by the ribosome into a (proto) protein.

The function of a protein is almost always dependent on how it is folded. When proteins are constructed on the ribosome, one amino acid is added at a time. There are ribosomal proteins which fold and trim amino acids from the proto-protein as it is being assembled.

When a protein is released into the cytoplasm from the ribosome it has a predictable shape. In many proteins that shape is fixed. Some proteins can be reshaped. Hemoglobin is a well known example.

comparative genomics

You have probably heard statements like 'chimpanzees have 98% of their DNA in common with humans, or some idea that 'genetics' shows humans are more closely related to chimpanzees than to gorillas. The field in biology which studies and compares the genomes of different organisms is comparative genomics.

A major aim of this section is to demonstrate how crude the experiments are on which these kinds of claims are based

Strands of DNA, at room temperature, bind in pairs. As the DNA is heated this bonding breaks down, and a sample of human DNA 'melts' (dissociates) at around 85 degrees Celsius.

If human DNA is 'melted' and mixed with say, melted chimp DNA, as the mixture cools the DNA strands pair up (reanneal).

The experimental techniques used in DNA hybridization experiments allow the human-human and chimp-chimp strands to be removed. What is left are human-other species strands. Because there is not a one to one corrrespondence between the bases on the strands these melt at a lower temperature. Typically, there is about a one degree drop in the 'melting point' for every one percent difference in the DNA sequence.

As the techniques if DNA hybridization were developed before those of genome sequencing it is important to realize that the results are estimates, based on sequencing of regions only of chromosomes

DNA hybridization says nothing about where the differences occur. They might be random over the length of the chromosome or clustered in various regions. They might effect every gene, or only the areas of 'junk' DNA occurring between gene sequences.

If the nucleotide sequence of a specifc gene found in a number of species is determined for each of those species, then the number of bases that are different is easily worked out.

This has two applications. The first, and least controversial, is that roughly speaking, the species with the most bases in common diverged from a common ancestot most recently. I say roughly apeaking, because if different genes are sequenced the results can be different. So some sort of averaging is required. However, comparing gene base sequences produces a similar 'tree of life' (model of common ancestry) to that of the fossil record. So, comparing gene sequences produces results consistent with evolution by descent from a common ancestor.

These differences in the base sequences of genes across species are also used, controversially, to estimate when the species diverged from their common ancestor. The idea is that a change in a base represents a non-harmful mutation. If we know the mutation rate and if that mutation rate has been constant over geological time, then we have an estimate of how long ago the species diverged from a common ancestor. The problem is that the mutation rate is uncertain.

epigenetics

In this course, epigenetics means the study of how chemical products of parental acquired characteristics (epenes or epigenetic factors) influence the phenotype of offspring.

For example, fat male mice have been shown to father fat child mice. The same male mice before they became fat (and after they were placed on a diet) did not beget fat child mice.

In this case obesity is an acquired characteristic, and the transmission of obesity to offspring seems to be by way of micro-RNA that accompanies the mouse sperm.

The 1944 Dutch famine occurred because the Nazis restricted food supplies to parts of Holland. The children of women who were pregnant at this time had high rates of obesity, diabetes, and cardiovascular disease as adults. Moreover, their grandchildren were small (as the daughters had been).

This is an example of maternal nutrition affecting the long term health of babies – an epigenetic phenomenon. The mothers, who were starved, set the embryos to a ‘starved’ state (so called ‘fetal programming’). When the embryos were born into a world where the food supply was normal they grew up with the diseases of over-nutrition.

In the second half of the nineteenth century Darwinians fought, and won (for the time), a battle with the followers of Jean-Baptiste Lamarck. Lamarck argued that acquired characteristics could be passed from parents to children. According to Lamarck, acquired characteristics were those that were developed through use (such as muscles).

Darwinians rejected this idea. Inherited characteristics were those present at birth, and they were the only ones that could be transmitted to offspring.

The rise of epigenetics is also the rebirth of Lamarck. Some acquired characteristics can be inherited.

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R M Cullen

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