The Evolution of the Mammalian ABCA6-like Genes: Analysis of Phylogenetic, Expression, and Population Genetic Data Reveals Complex Evolutionary Histories

ABC membrane transporters are a large and complex superfamily of ATP-binding cassette transporters that are present in all domains of life. Both their essential function and complexity are reflected by their retention across large expanses of organismal diversity and by the extensive expansion of individual members and subfamilies during evolutionary history. This expansion has resulted in the diverse ABCA transporter family that has in turn evolved into multiple subfamilies. Here, we focus on the ABCA6-like subfamily of ABCA transporters with the goal of understanding their evolutionary history including potential functional changes in, or loss of, individual members. Our analysis finds that ABCA6-like genes, consisting of ABCA6, 8, 9, and 10, are absent from representatives of both monotremes and marsupials and thus the duplications that generated these families most likely occurred at the base of the Eutherian or placental mammals. We have found evidence of both positive and relaxed selection among the ABCA6-like genes, suggesting dynamic changes in function and the potential of gene redundancy. Analysis of the ABCA10 genes further suggests that this gene has undergone relaxed selection only within the human lineage. These findings are complemented by human population data, where we observe an excess of deactivating homozygous mutations. We describe the complex evolutionary history of this ABCA transporter subfamily and demonstrate through the combination of evolutionary and population genetic analysis that ABCA10 is undergoing pseudogenization within humans.