Trends in Genetics
ReviewPrimate comparative genomics: lemur biology and evolution
Introduction
The motivation behind many comparative genomic sequencing efforts in primates is focused on advancing our understanding of the human genome and its origins. The complete sequence of the chimpanzee, for example, which became available in 2005, provided for the first time a comprehensive basis for exploring what makes us different from our closest evolutionary relative [1]. The addition of the sequences of the macaque (in progress) and orangutan (in progress) will further define aspects of human genome architecture and sequence variation. Adding sequence from a basal primate, such as a lemur, will provide depth to primate sequence comparisons and will allow for a more complete understanding of primate genome evolution. There are over 50 different species of lemurs [2], including the only hibernating primates, as well as families with high chromosome number variation. Currently, only a single lemur representative, the gray mouse lemur (Microcebus murinus), is being sequenced at an intermediate grade of coverage (http://www.genome.gov/10002154) [3]. Many of these different lemur species have characteristics specific to them and can provide novel research opportunities (Figure 1; Table 1; Box 1).
Similar to genome sequencing efforts, comparative primate karyotype studies have addressed how understanding the organization of other primate chromosomes can inform us about the evolution of our own karyotype 4, 5, 6. Chromosome painting and banding experiments have enabled reconstruction of the ancestral primate karyotype 4, 7 but we still do not understand the mechanisms involved or the potential functional changes associated with chromosome rearrangements. Comparative cytogenetic studies, when coupled with genome sequences, will allow correlation of functional aspects of primate genomes with chromosome rearrangements and will offer insight into how primate chromosomes have changed through evolutionary time.
Lemurs are particularly well suited for studies of chromosome rearrangements because there are numerous closely related species (<10 million years apart) whose chromosome number varies over a wide range, much more so, for example, than that seen among great ape genomes [8]. Owing to the large number of chromosome rearrangements between some species, comparative chromosome studies will be useful to identify common chromosome breakpoints. Evolutionary breakpoints have been correlated with human diseases and fragile sites and thus might provide clues into the basis for these human diseases [7]. Future functional studies can then address aspects of gene expression changes or potential epigenetic modifications associated with the rearrangements.
Here we review what is known cytologically and phylogenetically about lemur genomes and discuss how genome sequencing and comparative chromosome studies using these basal primates will contribute to understanding aspects of primate biology, genetics, ecology and evolution.
Section snippets
Lemur phylogenetics
Based on the earliest primate fossil dated to 55 million years ago (Mya), extrapolations have indicated that the most recent common ancestor of humans and prosimians existed over 80 Mya [8]. Figure 2 depicts the generally accepted phylogeny of primates and a more detailed suggested phylogeny of lemurs.
In all studies, the Daubentoniidae family [of which the Aye-aye (Daubentonia madagascariensis) is a member] has been shown to be the first to diverge from all other lemur families 8, 9, 10, 11, 12
Lemur chromosomes
Lemur chromosome numbers are strikingly variable and offer numerous opportunities to reconstruct ancestral karyotypes and to study chromosome rearrangements, evolution and speciation. Even though most lemur genomes are similar in size to the human genome [23], their diploid (2n) chromosome number varies from 20 to 70 (Table 2). The chromosome number does not seem to correlate well with evolutionary distance, as, for example, the fat-tailed dwarf lemur (Cheirogaleus medius) and the gray mouse
Lemur genome comparisons
To correlate chromosome rearrangements with genome sequence features, whole-genome sequences will be a necessity. Arguably, primate comparative genomics will be best served by adding more diverse species, as multiple genome alignments allow tracing evolutionary histories for genes and non-coding sequences and offer information about evolutionary distances 69, 70, 71. Two prosimians, the small-eared galago (Otolemur garnnetti) and the gray mouse lemur, have comparative-grade genome sequence
Conclusions
Lemur comparative genomics and cytogenetics has the opportunity to answer numerous biological, evolutionary and biomedical questions with relevance to humans and bring us closer to an understanding of how the primate genome has evolved. With improvements to the technology available for genome-wide sequence comparisons, we will have the ability to ask more refined questions about chromosome and species evolution. Comparative genomic sequencing of more primates, including lemurs, will facilitate
Acknowledgements
We thank Elliott Margulies for lemur genome sequence comparisons and Greg Wray, Anne Yoder, Karen Hayden, David Lowry, Jenny Tung and Mohamed Noor for thoughtful discussions. JEH was supported in part by a fellowship from the Center for Evolutionary Genomics in the Institute for Genome Sciences and Policy at Duke University.
Glossary
- Acrocentric chromosome
- a chromosome with the centromere near one end.
- Bivalent
- a pair of homologous chromosomes that synapse during the first meiotic division.
- Family
- the taxonomic category above genus (e.g. Cheirogaleidae).
- Genus
- the taxonomic category above species (e.g. Microcebus).
- Heteromorphic trivalent
- a chromosome form during the first meiotic division composed of three different synapsed partially homologous chromosomes.
- Lemur
- all prosimian primates endemic to the island of Madagascar and
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