Evolution of multigene families: histone and major histocompatibility complex genes

Open Access
- Author:
- Piontkivska, Olena
- Graduate Program:
- Genetics
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- March 03, 2003
- Committee Members:
- Masatoshi Nei, Committee Chair/Co-Chair
Claude Walker Depamphilis, Committee Member
David Michael Geiser, Committee Member
Zhi Chun Lai, Committee Member
Richard W Ordway, Committee Member - Keywords:
- histone
H3
H4
multigene family
concerted evolution
birth-and-death evolution
purifying selection
MHC
class I
divergence time
primates - Abstract:
- To understand the mode and mechanism of evolution of multigene families, I studied the evolutionary pattern of the highly conserved histone H3 and H4 and the highly divergent MHC gene families. (1) The primary purpose of the study of the histone H3 gene family was to investigate whether this family has evolved following the model of concerted evolution as was claimed by some previous authors. The results of the phylogenetic analysis of H3 genes from animals, plants and fungi indicated that while H3 protein sequences are highly conserved even between different kingdoms, the level of nucleotide sequence divergence at silent sites is generally very high and often close to the saturation level. These results suggest that the high degree of conservation of H3 proteins is primarily caused by purifying selection and that H3 nucleotide sequences evolve following the model of birth-and-death evolution. This study also suggested that the replication-dependent H3 genes may have evolved from the replication-independent H3 genes. (2) Histone H4 protein is among the most highly conserved proteins in eukaryotes. Statistical and phylogenetic analyses of the protein and DNA sequences of H4 genes from various organisms showed that the evolutionary pattern of this gene family is essentially the same as that of the H3 gene family. That is, the sequence homogeneity of H4 proteins is primarily caused by purifying selection, whereas nucleotide sequences evolve following the birth-and-death model of evolution. My study also indicated that all five classes of histone genes (H1, H2A, H2B, H3 and H4) were derived from archaebacteria rather than from eubacteria and that they diverged at nearly the same time before the separation of eukaryotic kingdoms, protists, plants, fungi and animals. (3) It has been suggested that MHC genes are subject to birth-and-death evolution with a high rate of gene turnover, but the rate of gene turnover has never been studied. To obtain some insight into this problem, I estimated the time of occurrence of gene duplication events that generated new MHC loci as well as the times of divergence of allelic lineages in polymorphic MHC class I loci of primate species. The results showed that one of these loci, namely locus F, diverged from the other loci about 46-66 million years ago (MYA). Other class I loci such as classical locus C in great apes and the duplicated B locus in macaques have appeared relatively recently about 21-28 MYA. The major diversification of class I loci was estimated to have occurred about 35-49 MYA, which is before the time of separation of Old World -New World monkeys. The most recent common ancestors of different allelic lineages at the A, B and C loci in humans were estimated to have appeared at least 14-19, 10-15 and 13-17 MYA, respectively. These results suggest that the rate of gene turnover in primate MHC class I genes is indeed quite rapid, as was previously conjectured.