Two-Parameter Characterization of Chromosome-Scale Recombination Rate

📝 Abstract

The genome-wide recombination rate ( $RR $) of a species is often described by one parameter, the ratio between total genetic map length ( $G$) and physical map length ( $P$), measured in centiMorgans per Megabase (cM/Mb). The value of this parameter varies greatly between species, but the cause for these differences is not entirely clear. A constraining factor of overall $RR$ in a species, which may cause increased $RR$ for smaller chromosomes, is the requirement of at least one chiasma per chromosome (or chromosome-arm) per meiosis. In the present study, we quantify the relative excess of recombination events on smaller chromosomes by a linear regression model, which relates the genetic length of chromosomes to their physical length. We find for several species that the two-parameter regression, $G= G_0 + k \cdot P$ provides a better characterization of the relationship between genetic and physical map length than the one-parameter regression that runs through the origin. A non-zero intercept ( $G_0 $) indicates a relative excess of recombination on smaller chromosomes in a genome. Given $G_0 $, the parameter $k$ predicts the increase of genetic map length over the increase of physical map length. The observed values of $G_0$ have a similar magnitude for diverse species, whereas $k$ varies by two orders of magnitude. The implications of this strategy for the genetic maps of human, mouse, rat, chicken, honeybee, worm and yeast are discussed.

💡 Analysis

The genome-wide recombination rate ( $RR $) of a species is often described by one parameter, the ratio between total genetic map length ( $G$) and physical map length ( $P$), measured in centiMorgans per Megabase (cM/Mb). The value of this parameter varies greatly between species, but the cause for these differences is not entirely clear. A constraining factor of overall $RR$ in a species, which may cause increased $RR$ for smaller chromosomes, is the requirement of at least one chiasma per chromosome (or chromosome-arm) per meiosis. In the present study, we quantify the relative excess of recombination events on smaller chromosomes by a linear regression model, which relates the genetic length of chromosomes to their physical length. We find for several species that the two-parameter regression, $G= G_0 + k \cdot P$ provides a better characterization of the relationship between genetic and physical map length than the one-parameter regression that runs through the origin. A non-zero intercept ( $G_0 $) indicates a relative excess of recombination on smaller chromosomes in a genome. Given $G_0 $, the parameter $k$ predicts the increase of genetic map length over the increase of physical map length. The observed values of $G_0$ have a similar magnitude for diverse species, whereas $k$ varies by two orders of magnitude. The implications of this strategy for the genetic maps of human, mouse, rat, chicken, honeybee, worm and yeast are discussed.

📄 Content

arXiv:0909.2682v1 [q-bio.GN] 14 Sep 2009 Two-Parameter Characterization of Chromosome-Scale Recombination Rate Wentian Li and Jan Freudenberg The Robert S. Boas Center for Genomics and Human Genetics The Feinstein Institute for Medical Research North Shore LIJ Health System Manhasset, 350 Community Drive, NY 11030, USA. ABSTRACT: The genome-wide recombination rate (RR) of a species is often described by one parameter, the ratio between total genetic map length (G) and physical map length (P), measured in centiMorgans per Megabase (cM/Mb). The value of this parameter varies greatly between species, but the cause for these differences is not entirely clear. A constraining factor of overall RR in a species, which may cause increased RR for smaller chromosomes, is the requirement of at least one chiasma per chromosome (or chromosome-arm) per meiosis. In the present study, we quantify the relative excess of recombination events on smaller chromosomes by a linear regression model, which relates the genetic length of chromosomes to their physical length. We find for several species that the two-parameter regression, G = G0 + k · P provides a better characterization of the relationship between genetic and physical map length than the one-parameter regression that runs through the origin. A non-zero intercept (G0) indicates a relative excess of recombination on smaller chromosomes in a genome. Given G0, the parameter k predicts the increase of genetic map length over the increase of physical map length. The observed values of G0 have a similar magnitude for diverse species, whereas k varies by two orders of magnitude. The implications of this strategy for the genetic maps of human, mouse, rat, chicken, honeybee, worm and yeast are discussed. 1 Li and Freudenberg 2 Introduction The rate of meiotic recombination rate (RR), defined as the ratio between genetic and physical map length and measured in centiMorgan per Megabase (cM/Mb), is known to vary widely between the genomes of different species. As a rule of thumb for the human genome, 1cM genetic map length equals 1Mb physical map length, see e.g. (Collins and Morton 1998; Ulgen and Li 2005). This rate is about twice as large as the genome-wide RR observed in the mouse genome (Jense-Seaman et al. 2004), but far less than the RR of 340cM/Mb that is ob- served in the yeast genome (Mortimer et al. 1992; Baudat and Nicolas 1997). Understanding of these differences in RR between different species is of fundamental importance for evolution- ary and medical genetics (Nachman 2002). In addition to these differences between species, it was also noted that RR differs between chromosomes within a species, with smaller chro- mosomes showing higher RR (Nachman and Churchill 1996; Broman et al. 1998; Lander et al. 2001; Venter et al. 2001; Kong et al. 2002; Matise et al. 2007). Therefore, species differences in genome-wide RR may be best studied under a model that also considers the intragenomic differences between chromosomes. From a population genetic perspective, the main role of recombination is the produc- tion of new combinations of alleles by shuffling of parental haplotypes, which increases the efficiency of natural selection in theoretical and empirical model systems (Maynard-Smith 1978; Barton and Charlesworth 1998; Rice 2002; Otto and Lenormand 2002). Many recent empirical studies have addressed the question at which sites in a genome recombination is most likely to occur (Petes 2001; McVean et al. 2004; Hey 2004; Myers et al. 2005; Coop 2005; Mancera et al. 2008). In this context it was also found that RR evolves extremely fast on a kb-scale (Ptak et al. 2005; Winckler et al. 2005) and that historical recombina- tion hotspots are associated with specific gene functions in human, which was hypothesized to indicate an influence of natural selection on hotspot locations (Freudenberg et al. 2007; The International HapMap Consortium 2007). When RR is examined at a megabase scale in- stead of a kilobase scale, the evolution of local RR is more constrained (Myers et al. 2005), and differs much less between closely related species, such as human and chimpanzees (Winckler et al. 2005; Ptak et al. 2005). However, the mechanism behind this conservation of RR on the larger Li and Freudenberg 3 scale is unclear. One contributing explanation could be the requirement of a minimal or fixed number of chiasmata per chromosome during meiosis to stabilize homologous chromosome pairs (Mather 1938). The question how many chiasmata are exactly required per chromosome or per chromosome arm has not been resolved yet and might not have a generally valid answer (Lynn et al. 2004; Laurie and Hult´en 1985). Nevertheless, these meiotic constraints can explain the excess of recombination on shorter chromosomes. Consistent with an influence of karyotype on over- all recombination rate, a correlation was found between the number of chromosome arms in a genome and the genetic map length (De Villena and Sapienza 2001a)

This content is AI-processed based on ArXiv data.