Study Assesses Genes

According to a recent Cornell study, non-African populations tend to have less genetic diversity than African populations. The study reinforced historical studies about out-of-Africa migration, while presenting additional information about the genetic effect of this migration.
Kirk Lohmueller grad, the primary author of the paper, “Proportionally More Deleterious Genetic Variation in European than in African Populations,” explained that scientists have been studying the genetic divisions in varying populations for years. Cornell scientists have noticed that non-African populations tend to have less genetic diversity than African populations from previous genetic studies. This finding ties back to the historic migration of human beings out of Africa.
Lohmueller explained that previously, the parts of the human genome that were studied were exclusively neutral markers. These non-coding regions of the genome do not create protein, which is the purpose of genetic material. Since these genes do not have as significant of a function, the studies on neutral markers produce more historical mapping on the migration of humans.
Because neutral markers have no impact on genetic fitness, the scientists theorized that if they were to use markers that effect fitness, it would be more telling of the similarities and differences between the genome in African-Americans and that of European-Americans.
Lohmueller and his team studied genes that were translated and transcribed into proteins.
“We used sequencing data from the coding region of the genome which is the part that gets translated into proteins. We had sequencing from 15 African-American individuals and 20 from European-American individuals,” Lohemuller said.
“We wanted to see if population history has impacted neutral markers differently from non-neutral markers. In our case we looked at synonymous SNPs [single-nucleotide polymorphisms] and non-synonymous SNPs,” Loehmuller said.
These synonymous SNPs, when changed in the base pair of guanine, adenine, cytosine and thymine, do not result in a change in the amino acid or protein because of the redundancy of the genetic code. This redundancy comes from the fact that amino acids can be coded by more than one triplet code.
“We believe that because you are now changing the amino acid, which could change the overall shape of the protein, it would have much more of a functional change which would affect fitness,” Lohmueller said.
In studying these non-synonymous and synonymous SNPs, Lohmueller and the other scientists counted the number of SNPs for both populations. It was not surprising to Lohmueller that for the African-American genes, there was a higher ratio of both synonymous and non-synonymous SNPs. He explained that this was to be assumed because humans migrated out of Africa, which contributed to a loss of genetic diversity.
What was interesting to the scientists was that a higher proportion of the European-American SNPs were non-synonymous compared to the African-Americans non-synonymous SNPs.
“Not all changes to the amino acid sequence are the same,” Lohmueller explained. “Some amino acids are more chemically similar to each other or the protein change could make less of an impact on some [parts of the protein] more than others. What we wanted to do was try to say which of these non-synonymous SNPs are most likely to affect protein function. Do we see that there is proportionally SNP’ more in Europe that were more likely to damage the protein?”
In trying to predict which SNPs would be more harmful, a Harvard Medical School computer program was used to predict the effect on the protein. The program considers the protein structures and then uses the placement of the snip to classify each as being either benign, probably damaging or possibly damaging.
The outcome of these predictions was that about 16 percent of European-American non-synonymous SNPs are probably damaging, as opposed to the 12 percent of African-American SNPs considered harmful.
Carlos Bustamante, the senior author of the paper and assistant professor of biological statistics and computational biology, was careful to distinguish that these results do not imply that one set of genes is better, more fit or healthier than the other. Such factors are generally effected by more than genetic makeup alone.
The scientific paper, which was published in Nature, stated that “Given the lower levels of genetic diversity found in Europeans than in Africans, the former have a higher proportion of deleterious alleles, which can be explained by the ‘out of Africa’ bottleneck and subsequent expansion that outbred European populations endured.”
Lohmueller explained that the migration refers to the small population of Africans who migrated from Africa and populated the rest of the world relatively quickly. He predicts that over time, natural selection will remove these deleterious effects.
“We think the results are interesting from the perspective of understanding human population genetics, and suggest that ancient demographic events can be detected today from patterns of genetic variation. We also found that every person in our sample, regardless of African or European origin, carried hundreds of mutations predicted to impact protein structure and stability,” Bustamante stated in an email. “It is not possible to say what the medical implications of this are yet, but we believe they suggest medical re-sequencing (comparing genome sequences of individuals with and without disease) may be useful since there seem to be plenty of mutations in everyone’s genomes disrupting protein structure and stability.”