The Article
below is the link to the full article that i outlined and summarized.
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hiv_resistant_gene.pdf Size : 372.516 Kb Type : pdf |
Article Outline
The Geographic Spread
of the CCR5 D32 HIV-Resistance Allele
I. Introduction
A. The spread of advantageous alleles is important to evolutionary processes. The CCR5 D32 allele plays an important role in HIV resistance among hetero and homozygous carriers.
i. The mutation is mostly found in Europe and western Asia, where the average occurrence is 10%. DNA evidence suggests that the allele is at least 2,900 years old. Smallpox is believed to be the selective agent.
ii. Heterozygous carriers have a reduced susceptibility to the onset of Aids. While Homozygous carriers are resistant to HIV.
B. This research is being done to discover the origin of the D32 allele, and what affected its spread.
i. Higher frequencies of the D32 are found in northern Europe, Particularly the Baltic region, with lower occurrences in Italy, and Greece. The spread towards the north implies a Viking origin, somewhere around 1,200 years ago.
ii. The advantage of the D32 in northern Europe can also be explained by higher intensity of smallpox in the region. Making selection intensity much more prevalent in the north for the D32.
C. The Hypothesis they make, is that given the young age of the D32, the allele must have spread rapidly, through long range dispersal , and intense selection to be where it is today.
II. Materials and Methods
A. Land mass data was used focusing the tests from 22°N to 75°N, and 10°W to 154°E. Topographic data was obtained from the National Geophysical Data Center.
B. Frequency of alleles was mapped by compiling data from multiple sources. The results would be categorized by longitude or latitude or the major city in that region.
C. Used a PDE model which describes change in allele frequency at any point in the range in terms of the effects of dispersal
III. Results
A. The PDE model that was used gave results that would be similar to real data, instead of just samples.
B. The estimated origin shifts from Iceland to Western Europe in what is now Spain, or as well in Germany.
C. Dispersal is key in the spread and frequency of the D32 allele. This is shown through gradients of selection intensity, and also consistent with the evidence of small pox being more prevalent in the north.
IV. Discussion
A. The results suggest a strong selection of 10%, and dispersal of 100km, are necessary to explain the spread and dispersal of D32.
B. A discrepancy was found in the distance of dispersal, showing only 75km distance spread from historical records, but these records didn’t take into account longer distance dispersal through trade routes or population movements.
C. Geographically restricted distribution of D32 is explained by its young age and not having enough time to disperse. Given more time it would have reached a much broader area.
D. Varying degree of Dominance in alleles would have little or no effect on dispersal.
E. Analysis confirms D32 has been under strong selection, and long range dispersal is important in the spread of the advantageous allele in humans.
Article Summary
The Geographic Spread of the CCR5 D32
HIV Resistance Allele
Introduction
The spread of the CCR5 D32 allele is important in resistance against Human Immunodeficiency Virus (HIV), in hetero and homozygous carriers of the allele. The D32 allele is figured to be around 2900 years old, and is thought to have come from Smallpox being its selective agent. Heterozygous carriers have a reduced susceptibility to Acquired Immune Deficiency Syndrome (Aids), while homozygous carriers are completely resistant.
The scientists are carrying out this research to find out when and where the D32 allele originated from and what effected its spread. There is a higher concentration of the D32 allele in the northern regions of Europe, with lower occurrences of the allele in the south towards Italy and Greece. It is thought the Vikings were the cause of the spread to the north. There was also a higher intensity of Smallpox in the northern regions of Europe, which could explain its spread there.
The scientists hypothesis was that the D32 must have spread quickly, through a long-range dispersal, and been intensely selected to be at the volume it’s at today.
Materials and Methods
The scientists used data from 22°N to 75°N, and 10°W to 154°E. Which covers most of Europe so they could isolate the spread in that region. Topographic data was obtained from the National Geophysical Data Center.
The scientists mapped the frequency of the D32 allele by compiling their data from different sources and sorted them by longitude, latitude or the major city that data was closest to. They also used a Partial Differential Equation model (PDE), which describes change in allele frequency at any point in the range in terms of the effects of dispersal since it has multiple variables.
Results
The PDE model was good for the research because it gave results that would be similar to actual data, making the results more accurate.
The origin from their hypothesis now shifts to Western Europe, showing the origin more towards Spain and as well Germany. Because of this, the dispersal is thought to be key in the D32’s spread. Also Strong selection still plays a roll in the quick spread of the allele.
Discussion
The results from the scientist’s research suggest that a strong selection of 10% and dispersal over 100 Kilometers (km) is necessary to explain the spread of the D32. There was a fault with historical records showing dispersal of only 75km, but this didn’t take into account longer dispersals such as trade routes and population movements, which increased the distance.
The D32 allele shows some restriction in its spread mostly due to its limited time that it has had to disperse. Given more time the area would be much broader.
It was also found in the research that the dominance of alleles had little or no effect on the spread of the D32 allele. All of the research points to the allele having been spread mostly due to long-range dispersal, and as well strong selection.
