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Estimates of Evolutionary Rate, Date and Migration of Hepatitis B Virus Genotypes A and D

Ali, Mina (2012) BINP31 20111
Degree Projects in Bioinformatics
Abstract
Abstract

To estimate the timescale of hepatitis B virus (HBV) evolutionary history and analyzing its phylogeographic patterns, publically available HBV sequences were collected from GenBank. Among those, 412 sequences were from genotype A and 566 sequences were from genotype D. These sequences comprised the entire genome and represented samples obtained between 1982 and 2009 from different parts of the world.
We first investigated different genome regions and compared the best resolved phylogenies among them. For this purpose, we analysed 5 different genome regions of genotype A and found that the core and polymerase genome region and partially full-length genomes containing only the non-overlapping regions produced almost equally... (More)
Abstract

To estimate the timescale of hepatitis B virus (HBV) evolutionary history and analyzing its phylogeographic patterns, publically available HBV sequences were collected from GenBank. Among those, 412 sequences were from genotype A and 566 sequences were from genotype D. These sequences comprised the entire genome and represented samples obtained between 1982 and 2009 from different parts of the world.
We first investigated different genome regions and compared the best resolved phylogenies among them. For this purpose, we analysed 5 different genome regions of genotype A and found that the core and polymerase genome region and partially full-length genomes containing only the non-overlapping regions produced almost equally resolved phylogenies. The commonly sequenced surface region produced only partially resolved phylogenies as compared to shorter non-overlapping regions, including the core and polymerase regions.
We next used Maximum Likelihood and Bayesian phylogenetic approaches to identify monophyletic clusters in HBV genotype A and D. 10 and 6 monophyletic clusters were found for Genotype A and D, respectively, each with a clear division according to geographic regions. A Bayesian Markov Chain Monte Carlo (MCMC) approach, as implemented in the Beast package, was used to estimate the HBV evolutionary rate and dates. The median rate of evolution in genotype A was 1.85 (95% HPD 0.192- 3.81) × 10−4 substitutions per site per year and the median root height was estimated to year 1747 (95% HPD 1059-1928). In genotype D, the median rate of evolution was 2.19 (95% HPD 0.54- 4.51) × 10−4 substitutions per site per year and the median root height was estimated to year
1745(95% HPD 1346-1913). The evolutionary rate values are in the range of previous estimates, whereas our tMRCA estimates are older than previously reported. The Bayesian skyline plot analysis for genotype A, showed a rapid growth of effective infections between 1960 and 1980 which coincided with the appearance and rapid growth of HBV genotype A in Europe. Genotype D showed a growth during the first half of the 20th century.
Finally, the phylogeographic patterns were determined based on the results of maximum clade credibility (MCC) tree and visualized in Google Earth using the SPREAD package. This analysis indicated that HBV genotype A was first introduced in Caribbean, and then spread to Africa and Europe. Genotype D had its origin in Europe from where it later moved into Asia. From our analysis, we conclude that HBV genotypes A and D have a recent origin (in the end of the 18th century) and have likely spread through different human migrations and activities. Genotype A had its roots in the Americas and was introduced into Africa and Europe during the late 18th century and experienced epidemic growth in Europe during the 1960s. Genotype D appeared in Europe and expanded during first half of the 20th century.

Popular science summary:

Estimates of Hepatitis B Virus Evolution Genotypes A and D

The study of emergence and spread of viral infections in human populations is an active and productive area of research in molecular epidemiology and virology. Hepatitis B virus (HBV) is a serious viral infection which infects the liver of hominoidea. Estimating the true evolutionary history of hepatitis B virus still remains controversial. It is due to existence of overlapping genomic regions, intergenotype recombination and usage of reverse transcriptase for replication.

To estimate the timescale of hepatitis B virus evolutionary history and analyzing its phylogeographic patterns, publically available HBV sequences were collected from GenBank. Among those, 412 sequences were from genotype A and 566 sequences were from genotype D. These sequences comprised the entire genome and represented samples obtained between 1982 and 2009 from different parts of the world.

We first investigated five different genome regions of genotype A and compared the best resolved phylogenies among them. Next, Maximum Likelihood and Bayesian phylogenetic approaches were used to identify monophyletic clusters in HBV genotype A and D. A Bayesian Markov Chain Monte Carlo (MCMC) approach was used to estimate the HBV evolutionary rate and date. Finally, the phylogeographic patterns were determined based on the results of maximum clade credibility (MCC) tree and visualized in Google Earth.

Results
We found that the core and polymerase genome region and partially full-length genomes containing only the non-overlapping regions produced almost equally resolved phylogenies. The surface region produced only partially resolved phylogenies. 10 and 6 monophyletic clusters were found for Genotype A and D, respectively. The median rate of evolution in genotype A was 1.85 (95% HPD 0.192- 3.81) × 10−4 substitutions per site per year and the median root height was estimated to year 1747 (95% HPD 1059-1928). In genotype D, the median rate of evolution was 2.19 (95% HPD 0.54- 4.51) × 10−4 substitutions per site per year and the median root height was estimated to year 1745(95% HPD 1346-1913).

Phylogeographic patterns analysis indicated that HBV genotype A had its roots in the Americas and was introduced into Africa and Europe during the late 18th century. It showed a rapid growth of effective infections between 1960 and 1980 which coincided with the appearance and rapid growth of HBV genotype A in Europe. Genotype D had its origin in Europe from where it later moved into Asia. It showed a growth during the first half of the 20th century.

Advisor: Patrik Medstrand
Master's Degree Project 45 credits in Bioinformatics.
Department of Biology, Lund University (Less)
Please use this url to cite or link to this publication:
author
Ali, Mina
supervisor
organization
course
BINP31 20111
year
type
H2 - Master's Degree (Two Years)
subject
keywords
Hepatitis B Virus, Phylogenetic Analysis, Evolution, Phylogeography
language
English
id
3611587
date added to LUP
2013-03-20 13:40:13
date last changed
2013-03-25 08:42:38
@misc{3611587,
  abstract     = {Abstract

To estimate the timescale of hepatitis B virus (HBV) evolutionary history and analyzing its phylogeographic patterns, publically available HBV sequences were collected from GenBank. Among those, 412 sequences were from genotype A and 566 sequences were from genotype D. These sequences comprised the entire genome and represented samples obtained between 1982 and 2009 from different parts of the world.
We first investigated different genome regions and compared the best resolved phylogenies among them. For this purpose, we analysed 5 different genome regions of genotype A and found that the core and polymerase genome region and partially full-length genomes containing only the non-overlapping regions produced almost equally resolved phylogenies. The commonly sequenced surface region produced only partially resolved phylogenies as compared to shorter non-overlapping regions, including the core and polymerase regions.
We next used Maximum Likelihood and Bayesian phylogenetic approaches to identify monophyletic clusters in HBV genotype A and D. 10 and 6 monophyletic clusters were found for Genotype A and D, respectively, each with a clear division according to geographic regions. A Bayesian Markov Chain Monte Carlo (MCMC) approach, as implemented in the Beast package, was used to estimate the HBV evolutionary rate and dates. The median rate of evolution in genotype A was 1.85 (95% HPD 0.192- 3.81) × 10−4 substitutions per site per year and the median root height was estimated to year 1747 (95% HPD 1059-1928). In genotype D, the median rate of evolution was 2.19 (95% HPD 0.54- 4.51) × 10−4 substitutions per site per year and the median root height was estimated to year
1745(95% HPD 1346-1913). The evolutionary rate values are in the range of previous estimates, whereas our tMRCA estimates are older than previously reported. The Bayesian skyline plot analysis for genotype A, showed a rapid growth of effective infections between 1960 and 1980 which coincided with the appearance and rapid growth of HBV genotype A in Europe. Genotype D showed a growth during the first half of the 20th century.
Finally, the phylogeographic patterns were determined based on the results of maximum clade credibility (MCC) tree and visualized in Google Earth using the SPREAD package. This analysis indicated that HBV genotype A was first introduced in Caribbean, and then spread to Africa and Europe. Genotype D had its origin in Europe from where it later moved into Asia. From our analysis, we conclude that HBV genotypes A and D have a recent origin (in the end of the 18th century) and have likely spread through different human migrations and activities. Genotype A had its roots in the Americas and was introduced into Africa and Europe during the late 18th century and experienced epidemic growth in Europe during the 1960s. Genotype D appeared in Europe and expanded during first half of the 20th century.

Popular science summary:

Estimates of Hepatitis B Virus Evolution Genotypes A and D

The study of emergence and spread of viral infections in human populations is an active and productive area of research in molecular epidemiology and virology. Hepatitis B virus (HBV) is a serious viral infection which infects the liver of hominoidea. Estimating the true evolutionary history of hepatitis B virus still remains controversial. It is due to existence of overlapping genomic regions, intergenotype recombination and usage of reverse transcriptase for replication.

To estimate the timescale of hepatitis B virus evolutionary history and analyzing its phylogeographic patterns, publically available HBV sequences were collected from GenBank. Among those, 412 sequences were from genotype A and 566 sequences were from genotype D. These sequences comprised the entire genome and represented samples obtained between 1982 and 2009 from different parts of the world.

We first investigated five different genome regions of genotype A and compared the best resolved phylogenies among them. Next, Maximum Likelihood and Bayesian phylogenetic approaches were used to identify monophyletic clusters in HBV genotype A and D. A Bayesian Markov Chain Monte Carlo (MCMC) approach was used to estimate the HBV evolutionary rate and date. Finally, the phylogeographic patterns were determined based on the results of maximum clade credibility (MCC) tree and visualized in Google Earth.

Results
We found that the core and polymerase genome region and partially full-length genomes containing only the non-overlapping regions produced almost equally resolved phylogenies. The surface region produced only partially resolved phylogenies. 10 and 6 monophyletic clusters were found for Genotype A and D, respectively. The median rate of evolution in genotype A was 1.85 (95% HPD 0.192- 3.81) × 10−4 substitutions per site per year and the median root height was estimated to year 1747 (95% HPD 1059-1928). In genotype D, the median rate of evolution was 2.19 (95% HPD 0.54- 4.51) × 10−4 substitutions per site per year and the median root height was estimated to year 1745(95% HPD 1346-1913).

Phylogeographic patterns analysis indicated that HBV genotype A had its roots in the Americas and was introduced into Africa and Europe during the late 18th century. It showed a rapid growth of effective infections between 1960 and 1980 which coincided with the appearance and rapid growth of HBV genotype A in Europe. Genotype D had its origin in Europe from where it later moved into Asia. It showed a growth during the first half of the 20th century.

Advisor: Patrik Medstrand
Master's Degree Project 45 credits in Bioinformatics.
Department of Biology, Lund University},
  author       = {Ali, Mina},
  keyword      = {Hepatitis B Virus,Phylogenetic Analysis,Evolution,Phylogeography},
  language     = {eng},
  note         = {Student Paper},
  title        = {Estimates of Evolutionary Rate, Date and Migration of Hepatitis B Virus Genotypes A and D},
  year         = {2012},
}